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254 Investigating the Relationship between Vitamin D and Persistent Symptoms Following SARS CoV 2 Infection The emergence of persistent symptoms following SARS CoV 2 infection known as i long COVID i is providing a new challenge to healthcare systems The cardinal features are fatigue and reduced exercise tolerance Vitamin D is known to have pleotropic effects far beyond bone health and is associated with immune modulation and autoimmunity We hypothesize that vitamin D levels are associated with persistent symptoms following COVID 19 Herein we investigate the relationship between vitamin D and fatigue and reduced exercise tolerance assessed by the Chalder Fatigue Score six minute walk test and modified Borg scale Multivariable linear and logistic regression models were used to evaluate the relationships A total of 149 patients were recruited at a median of 79 days after COVID 19 illness The median vitamin D level was 62 nmol L with i n i 36 24 having levels 30 49 nmol L and i n i 14 9 with levels 30 nmol L Fatigue was common with i n i 86 58 meeting the case definition The median Borg score was 3 while the median distance covered for the walk test was 450 m No relationship between vitamin D and the measures of ongoing ill health assessed in the study was found following multivariable regression analysis These results suggest that persistent fatigue and reduced exercise tolerance following COVID 19 are independent of vitamin D 1 |
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370 Baricitinib combination therapy a narrative review of repurposed Janus kinase inhibitor against severe SARS CoV 2 infection The Coronavirus disease 2019 COVID 19 pandemic is one of the most devastating global problems Regarding the lack of disease specific treatments repurposing drug therapy is currently considered a promising therapeutic approach in pandemic situations Recently the combination therapy of Janus kinase JAK inhibitor baricitinib has been authorized for emergency COVID 19 hospitalized patients however this strategys safety drug drug interactions and cellular signaling pathways remain a tremendous challenge In this study we aimed to provide a deep insight into the baricitinib combination therapies in severe COVID 19 patients through reviewing the published literature on PubMed Scopus and Google scholar databases We also focused on cellular and subcellular pathways related to the synergistic effects of baricitinib plus antiviral agents virus entry and cytokine storm CS induction The safety and effectiveness of this strategy have also been discussed in moderate to severe forms of COVID 19 infection The severity of COVID 19 is commonly associated with a dysregulated immune response and excessive release of pro inflammatory agents resulting in CS It has been shown that baricitinib combined with antiviral agents could modulate the inflammatory response and provide a series of positive therapeutic outcomes in hospitalized adults and pediatric patients age two years old Baricitinib plus the standard of care treatment might be a potential strategy in hospitalized patients with severe COVID 19 0 |
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295 Long lasting olfactory dysfunction in COVID 19 patients Olfactory dysfunction OD is a common symptom of Coronavirus Disease 2019 COVID 19 Although many patients have been reported to regain olfactory function within the first month long term observation reports vary Therefore we aimed to assess the course of chemosensory function in patients diagnosed with COVID 19 within 3 15 months after the infection One hundred and two patients 71 females and 31 males mean age 38 8 years diagnosed with laboratory confirmed COVID 19 and subjective OD participated in this single center study 111 457 days after onset of OD Patients first performed chemosensory tests at home followed by psychophysical testing Sniffin Sticks TDI 27 item Candy Smell Test CST Taste Strips Test TST in the clinic Questionnaires regarding importance of olfaction IOQ and olfactory specific quality of life QOD were applied at both timepoints After a mean 216 days SD 73 range 111 457 between OD onset and follow up testing the mean Sniffin Sticks TDI score was 27 1 points SD 5 8 range 4 25 38 5 4 0 were anosmic 72 5 hyposmic and 23 5 normosmic At follow up testing 73 5 of patients reported improvement 5 9 deterioration and 20 6 no change in OD Moreover full recovery of self perceived smell flavor and taste was not observed According to questionnaires the individual importance of smell did not change but participants showed improvement in OD related quality of life p 0 001 and had increased parosmia scores p 0 014 at follow up Our results show that long lasting OD after SARS CoV 2 infection is a common symptom The majority of patients had OD in the range of hyposmia which was confirmed by comprehensive smell tests 1 |
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242 Post acute and long COVID 19 symptoms in patients with mild diseases a systematic review It is expected that GPs are increasingly confronted with a large group of patients with symptoms persisting three weeks after initial symptoms of a mild managed in the outpatient setting COVID 19 infection Currently research on these persistent symptoms mainly focuses on patients with severe infections managed in an inpatient setting whereas patients with mild disease are rarely studied The main objective of this systematic review was to create an overview of the nature and frequency of persistent symptoms experienced by patients after mild COVID 19 infection Systematic literature searches were performed in Pubmed Embase and PsychINFO on 2 February 2021 Quantitative studies qualitative studies clinical lessons and case reports were considered eligible designs In total nine articles were included in this literature review The frequency of persistent symptoms in patients after mild COVID 19 infection ranged between 10 and 35 Symptoms persisting after a mild COVID 19 infection can be distinguished into physical mental and social symptoms Fatigue was the most frequently described persistent symptom Other frequently occurring persistent symptoms were dyspnoea cough chest pain headache decreased mental and cognitive status and olfactory dysfunction In addition it was found that persisting symptoms after a mild COVID 19 infection can have major consequences for work and daily functioning There is already some evidence that symptoms of mild COVID 19 persist after 3 weeks in a third of patients However there is a lack of data about symptoms persisting after 3 months long COVID More research is needed to help GPs in managing long COVID 1 |
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511 Mental health of parents of children with autism spectrum disorder during COVID 19 pandemic A systematic review Children diagnosed with autism spectrum disorder ASD may have great difficulties when their routines change and this may affect the psychological well being of their parents For this reason it is important to examine studies that address the mental health of parents in order to adapt to the coronavirus disease 2019 COVID 19 pandemic To determine the mental health status of parents with children diagnosed with ASD in the COVID 19 pandemic The study which is a systematic review was conducted between December 15 2020 and December 30 2020 by scanning articles in English The Scopus Science Direct PubMed Cochrane Web of Science and Google Scholar databases were used for scanning The keywords COVID 19 AND autism OR autistic OR autism spectrum disorder AND parent AND mental health OR anxiety OR stress were used in the search process The inclusion criteria in the study were findings regarding the mental health of parents with children diagnosed with ASD in the COVID 19 pandemic addressing their anxiety and stress situations being a research article and accessing the full text of the article In the study a total of 6389 articles were reached and the full texts of 173 articles were evaluated for eligibility After the articles excluded by the full text search were eliminated 12 studies involving 7105 parents were included in the analysis The findings obtained from the articles containing data on mental health in the COVID 19 pandemic of parents with children with autism spectrum disorder were discussed in three groups These were findings on the experiences of parents with children with ASD in the COVID 19 pandemic regarding the areas where parents with children with ASD need support in the COVID 19 pandemic and methods of coping with the COVID 19 pandemic for parents with children with ASD In the systematic review it was determined that the anxiety and stress of the parents increased they needed more support compared to the pre pandemic period and they had difficulty coping In this systematic review it was concluded that the COVID 19 pandemic negatively affected the mental health of the parents of children with ASD 0 |
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134 COVID 19 A Pneumological Point of View Long Term Sequelae of COVID 19 Implications For Follow up In Respiratory Medicine The long term sequelae of COVID 19 on are not yet predictable Radiological and histopathological data on COVID 19 and observational studies after the SARS CoV 1 pandemic 2003 2004 suggest that in a proportion of COVID 19 patients functional limitations due to pulmonary fibrosis and other patterns of lung damage may persist Systematic follow up based on prudent pulmonary function testing is warranted for the correct diagnosis graduation and treatment of the underlying pathology at an early stage This review summarizes the potential spectrum of Post COVID 19 pulmonary disease patterns and provides recommendations for the follow up care of COVID 19 patients in the field of respiratory medicine 1 |
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367 Clinical characteristics of COVID 19 in family clusters a systematic review Coronavirus disease 2019 COVID 19 caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 has spread around the world and reports of children during early epidemic period showed features of family clusters The aim of this study is to assess clinical profiles of COVID 19 in family clusters with children We performed a systematic literature review of English database PubMed Web of Science and Chinese database www cnki net www cqvip com and www Wanfangdata com cn to identify papers on family clusters of COVID 19 with children and their family members Eighteen studies involving 34 children and 98 adults from 28 families were included Fever cough and ground grass opacity change of chest computed tomography CT were the dominant features whereas proportion of asymptomatic infections for children was higher than adults with statistical significance 32 4 and 13 3 respectively P 0 05 Median time of longer incubation period 10 days and shorter duration of pharyngeal swab nucleic acid test positive period 11 days were seen in children than adults 7 and 17 days respectively with statistical significance P 0 05 There were statistically significant differences in lymphopenia increased C reactive protein and abnormal chest CT between children and adult patients P 0 05 Twenty seven families reported adults as first case of COVID 19 in family clusters The same virus strain can cause milder disease in children compared with their caregivers Children of COVID 19 were infected by adults in family during the early epidemic period Asymptomatic patients can transmit the virus 0 |
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307 Pan European Study on Functional and Medical Recovery and Geriatric Rehabilitation Services of Post COVID 19 Patients Protocol of the EU COGER Study There is insufficient knowledge about the functional and medical recovery of older people infected with SARS CoV 2 This study aims to gain insight into the course of functional and medical recovery of persons who receive geriatric rehabilitation GR following SARS CoV 2 infection across Europe Special attention will be paid to the recovery of activities of daily living ADL and to the GR services offered to these patients A multi center observational cohort study This study will include several European countries EuGMS member states each providing at least 52 comparable routine datasets core dataset of persons recovering from a SARS CoV 2 infection and receiving geriatric rehabilitation The routine data will be anonymously collected in an online CASTOR database The ethical regulations of each participating country will be followed ADL functioning length of stay discharge destination hospital readmission and mortality Other variables that will be collected are quality of life treatment modalities complications cognition frailty mood anxiety BMI nutrition and pain All variables will be reported at admission and compared with follow up scores discharge 6 weeks and 6 months follow up This study will explore the effect of geriatric rehabilitation on post COVID 19 patients especially on ADL recovery and the variety of geriatric rehabilitation services across Europe Information from this study may help improve recovery of older persons infected with SARS CoV 2 and improve geriatric rehabilitation services in the ongoing COVID 19 pandemic 1 |
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398 Big Data for Biomedical Education with a Focus on the COVID 19 Era An Integrative Review of the Literature Medical education refers to education and training delivered to medical students in order to become a practitioner In recent decades medicine has been radically transformed by scientific and computational digital advances including the introduction of new information and communication technologies the discovery of DNA and the birth of genomics and post genomics super specialties transcriptomics proteomics interactomics and metabolomics metabonomics among others which contribute to the generation of an unprecedented amount of data so called big data While these are well studied in fields such as medical research and methodology translational medicine and clinical practice they remain overlooked and understudied in the field of medical education For this purpose we carried out an integrative review of the literature Twenty nine studies were retrieved and synthesized in the present review Included studies were published between 2012 and 2021 Eleven studies were performed in North America specifically nine were conducted in the USA and two studies in Canada Six studies were carried out in Europe two in France two in Germany one in Italy and one in several European countries One additional study was conducted in China Eight papers were commentaries theoretical or perspective articles while five were designed as a case study Five investigations exploited large databases and datasets while five additional studies were surveys Two papers employed visual data analytical data mining techniques Finally other two papers were technical papers describing the development of software computational tools and or learning environments platforms while two additional studies were literature reviews one of which being systematic and bibliometric The following nine sub topics could be identified I knowledge and awareness of big data among medical students II difficulties and challenges in integrating and implementing big data teaching into the medical syllabus III exploiting big data to review improve and enhance medical school curriculum IV exploiting big data to monitor the effectiveness of web based learning environments among medical students V exploiting big data to capture the determinants and signatures of successful academic performance and counteract prevent drop out VI exploiting big data to promote equity inclusion and diversity VII exploiting big data to enhance integrity and ethics avoiding plagiarism and duplication rate VIII empowering medical students improving and enhancing medical practice and IX exploiting big data in continuous medical education and learning These sub themes were subsequently grouped in the following four major themes topics namely I big data and medical curricula II big data and medical academic performance III big data and societal bioethical issues in biomedical education and IV big data and medical career Despite the increasing importance of big data in biomedicine current medical curricula and syllabuses appear inadequate to prepare future medical professionals and practitioners that can leverage on big data in their daily clinical practice Challenges in integrating incorporating and implementing big data teaching into medical school need to be overcome to facilitate the training of the next generation of medical professionals Finally in the present integrative review state of art and future potential uses of big data in the field of biomedical discussion are envisaged with a focus on the still ongoing Coronavirus Disease 2019 COVID 19 pandemic which has been acting as a catalyst for innovation and digitalization 0 |
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382 Longitudinal observation of antibody responses for 14 months after SARS CoV 2 infection Better understanding of antibody responses against SARS CoV 2 after natural infection might provide valuable insights into the future implementation of vaccination policies Longitudinal analysis of IgG antibody titers was carried out in 32 recovered COVID 19 patients based in the Umbria region of Italy for 14 months after Mild and Moderately Severe infection Two FDA approved immunoassays against SARS CoV 2 Nucleocapsid protein NCP and anti spike receptor binding domain S RBD were used for sequential serological tests at different time points The demographics clinical history and symptom profile associated with the magnitude and longevity of antibody responses were also analyzed Anti S RBD IgG persisted in 96 8 31 of 32 subjects at 14 months Patients reporting loss of smell and taste during the clinical course of the disease developed significantly higher antibody titers Anti NCP IgG seronegative patients n 7 at 10 months tested positive for anti S RBD IgG at 12 13 and 14 months emphasizing on a higher false negative rate for NCP protein based antibody assays This study also highlights the importance of adopting specific immunoassays for routine estimation of antibody titers and the decreased rate of re infections in recovered patients 0 |
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40 COVID 19 and biomarkers of thrombosis focus on von Willebrand factor and extracellular vesicles COVID 19 caused by the SARS CoV 2 virus is responsible for a pandemic of unparalleled portion over the past century While the acute phase of infection causes significant morbidity and mortality post acute sequelae that can affect essentially any organ system is rapidly taking on an equally large part of the overall impact on human health quality of life attempts to return to normalcy and the global economy Herein we summarize the potential role of von Willebrand Factor and extracellular vesicles toward understanding the pathophysiology clinical presentation duration of illness diagnostic approach and management of COVID 19 and its sequelae 1 |
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418 Health Systems and Services During COVID 19 Lessons and Evidence From Previous Crises A Rapid Scoping Review to Inform the United Nations Research Roadmap for the COVID 19 Recovery This rapid scoping review has informed the development of the November 2020 United Nations Research Roadmap for the COVID 19 Recovery by providing a synthesis of available evidence on the impact of pandemics and epidemics on 1 essential services and 2 health systems preparedness and strengthening Emerging findings point to existing disparities in health systems and services being further exacerbated with marginalized populations and low and middle income countries burdened disproportionately More broadly there is a need to further understand short and long term impacts of bypassed essential services quality assurance of services the role of primary health care in the frontline and the need for additional mechanisms for effective vaccine messaging and uptake during epidemics The review also highlights how trust of institutions of science and between communities and health systems remains central to a successful pandemic response Finally previous crises had repeatedly foreshadowed the inability of health systems to handle upcoming pandemics yet the reactive nature of policies and practices compounded by lack of resources infrastructure and political will have resulted in the current failed response to COVID 19 There is therefore an urgent need for investments in implementation science and for strategies to bridge this persistent research practice gap 0 |
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377 Do school closures and school reopenings affect community transmission of COVID 19 A systematic review of observational studies To systematically reivew the observational evidence of the effect of school closures and school reopenings on SARS CoV 2 community transmission Schools including early years settings primary schools and secondary schools School closures and reopenings Community transmission of SARS CoV 2 including any measure of community infections rate hospital admissions or mortality attributed to COVID 19 On 7 January 2021 we searched PubMed Web of Science Scopus CINAHL the WHO Global COVID 19 Research Database ERIC the British Education Index the Australian Education Index and Google searching title and abstracts for terms related to SARS CoV 2 AND terms related to schools or non pharmaceutical interventions NPIs We used the Cochrane Risk of Bias In Non randomised Studies of Interventions tool to evaluate bias We identified 7474 articles of which 40 were included with data from 150 countries Of these 32 studies assessed school closures and 11 examined reopenings There was substantial heterogeneity between school closure studies with half of the studies at lower risk of bias reporting reduced community transmission by up to 60 and half reporting null findings The majority n 3 out of 4 of school reopening studies at lower risk of bias reported no associated increases in transmission School closure studies were at risk of confounding and collinearity from other non pharmacological interventions implemented around the same time as school closures and the effectiveness of closures remains uncertain School reopenings in areas of low transmission and with appropriate mitigation measures were generally not accompanied by increasing community transmission With such varied evidence on effectiveness and the harmful effects policymakers should take a measured approach before implementing school closures and should look to reopen schools in times of low transmission with appropriate mitigation measures 0 |
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153 Post COVID 19 arthritis a case report and literature review Severe acute respiratory syndrome coronavirus 2 SARS CoV2 is the novel pathogen responsible for the coronavirus disease 19 COVID 19 outbreak Researchers and clinicians are exploring the pathogenetic mechanisms of the viral induced damage and growing interest is focusing on the short term and long term immune mediated consequences triggered by the infection We will focus on post SARS CoV2 infection arthritis which may arise as a new pathological condition associated with COVID 19 In this article we describe a case of acute oligoarthritis occurring 13 days after a SARS CoV2 severe pneumonia in a middle aged Caucasian man and we go over a brief review of the current available literature We hypothesize that molecular mimicry might be the basic immunological mechanism responsible for the onset of COVID 19 related arthritis based on the current knowledge of SARS CoV2 and on the known pathogenetic mechanism of viral induced arthritis 1 |
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261 COVID 19 Disease Severity among People with HIV Infection or Solid Organ Transplant in the United States A Nationally representative Multicenter Observational Cohort Study Individuals with immune dysfunction including people with HIV PWH or solid organ transplant recipients SOT might have worse outcomes from COVID 19 We compared odds of COVID 19 outcomes between patients with and without immune dysfunction We evaluated data from the National COVID 19 Cohort Collaborative N3C a multicenter retrospective cohort of electronic medical record EMR data from across the United States on 1 446 913 adult patients with laboratory confirmed SARS CoV 2 infection HIV SOT comorbidity and HIV markers were identified from EMR data prior to SARS CoV 2 infection COVID 19 disease severity within 45 days of SARS CoV 2 infection was classified into 5 categories asymptomatic mild disease with outpatient care mild disease with emergency department ED visit moderate disease requiring hospitalization severe disease requiring ventilation or extracorporeal membrane oxygenation ECMO and death We used multivariable multinomial logistic regression models to compare odds of COVID 19 outcomes between patients with and without immune dysfunction Compared to patients without immune dysfunction PWH and SOT had a greater likelihood of having ED visits adjusted odds ratio aOR 1 28 95 confidence interval CI 1 27 1 29 aOR 2 61 CI 2 58 2 65 respectively requiring ventilation or ECMO aOR 1 43 CI 1 43 1 43 aOR 4 82 CI 4 78 4 86 respectively and death aOR 1 20 CI 1 19 1 20 aOR 3 38 CI 3 35 3 41 respectively Associations were independent of sociodemographic and comorbidity burden Compared to PWH with CD4 500 cells mm sup 3 sup PWH with CD4 350 cells mm sup 3 sup were independently at 4 4 5 4 and 7 6 times higher odds for hospitalization requiring ventilation and death respectively Increased COVID 19 severity was associated with higher levels of HIV viremia Individuals with immune dysfunction have greater risk for severe COVID 19 outcomes More advanced HIV disease greater immunosuppression and HIV viremia was associated with higher odds of severe COVID 19 outcomes Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID 19 among PWH and SOT 1 |
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494 Nanoparticles in the clinic An update post COVID 19 vaccines Nanoparticles are used in the clinic to treat cancer resolve mineral deficiencies image tissues and facilitate vaccination As a modular technology nanoparticles combine diagnostic agents or therapeutics e g elements small molecules biologics synthetic materials e g polymers and biological molecules e g antibodies peptides lipids Leveraging these parameters nanoparticles can be designed and tuned to navigate biological microenvironments negotiate biological barriers and deliver therapeutics or diagnostic agents to specific cells and tissues in the body Recently with the Emergency Use Authorization of the COVID 19 lipid nanoparticle vaccines the advantages and potential of nanoparticles as a delivery vehicle have been displayed at the forefront of biotechnology Here we provide a 5 year status update on our original Nanoparticles in the Clinic review also a 2 year update on our second Nanoparticles in the Clinic review by discussing recent nanoparticle delivery system approvals highlighting new clinical trials and providing an update on the previously highlighted clinical trials 0 |
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27 Rehabilitation setting during and after Covid 19 An overview on recommendations The aim of this review is to identify the best evidence to define rehabilitative approaches to acute and post acute phases of coronavirus 2019 COVID 19 disease A literature search of PubMed Google Scholar PEDro and Cochrane databases was perform ed for relevant publications from January to April 2020 A total of 2 835 articles were retrieved and the search resulted in a final total 31 published arti cles A narrative synthesis of the selected articles was then performed Some studies examine the effect of the pandemic on rehabilitation services and provide suggestions for a new reorganization of these services Other studies focus on COVID 19 sequelae formulating recommendations for rehabilitative interventions For COVID 19 patients an integrated rehabilitative process is recommended involving a multidisciplinary and multi professional team provid ing neuromuscular cardiac respiratory and swallowing interventions and psychological support in order to improve patients quality of life The intervention of a physician expert in rehabilitation should assess the patient and a dedicated intervention set up after thorough assessment of the patients clinical condition in collaboration with all rehabilitation team professionals 1 |
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300 Multisystem inflammatory syndrome in children related to COVID 19 An update regarding the presentation of two critically ill patients Multisystem inflammatory syndrome in children related to COVID 19 is defined as the presence of persistent fever inflammation and organ dysfunction with evidence of past or recent severe acute respiratory syndrome coronavirus 2 infection and excluding other microbial causes It overlaps with other inflammatory diseases Kawasaki disease and toxic shock syndrome and shares some features with hypercytokinemia conditions hemophagocytic lymphohistiocytosis and macrophage activation syndrome It differs from these and severe acute COVID 19 in its clinical presentation and laboratory parameters It has a potentially severe course and may occur with cardiovascular failure mortality is low 2 Here we provide an update on this syndrome and describe the presentation of two clinical cases with cardiovascular dysfunction who required vasoactive support and invasive ventilation Serum lab tests showed inflammation parameters Both patients were treated with intravenous immunoglobulin and systemic corticosteroids and had a favorable course 1 |
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265 Prevalence of post COVID 19 symptoms in hospitalized and non hospitalized COVID 19 survivors A systematic review and meta analysis Single studies support the presence of several post COVID 19 symptoms however no meta analysis differentiating hospitalized and non hospitalized patients has been published to date This meta analysis analyses the prevalence of post COVID 19 symptoms in hospitalized and non hospitalized patients recovered from COVID 19 MEDLINE CINAHL PubMed EMBASE and Web of Science databases as well as medRxiv and bioRxiv preprint servers were searched up to March 15 2021 Peer reviewed studies or preprints reporting data on post COVID 19 symptoms collected by personal telephonic or electronic interview were included Methodological quality of the studies was assessed using the Newcastle Ottawa Scale We used a random effects models for meta analytical pooled prevalence of each post COVID 19 symptom and I² statistics for heterogeneity Data synthesis was categorized at 30 60 and 90 days after From 15 577 studies identified 29 peer reviewed studies and 4 preprints met inclusion criteria The sample included 15 244 hospitalized and 9011 non hospitalized patients The methodological quality of most studies was fair The results showed that 63 2 71 9 and 45 9 of the sample exhibited one post COVID 19 symptom at 30 60 or 90days after onset hospitalization Fatigue and dyspnea were the most prevalent symptoms with a pooled prevalence ranging from 35 to 60 depending on the follow up Other post COVID 19 symptoms included cough 20 25 anosmia 10 20 ageusia 15 20 or joint pain 15 20 Time trend analysis revealed a decreased prevalence 30days after with an increase after 60days This meta analysis shows that post COVID 19 symptoms are present in more than 60 of patients infected by SARS CoV 2 Fatigue and dyspnea were the most prevalent post COVID 19 symptoms particularly 60 and 90 days after 1 |
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315 High dimensional characterization of post acute sequelae of COVID 19 The acute clinical manifestations of COVID 19 have been well characterized sup 1 2 sup but the post acute sequelae of this disease have not been comprehensively described Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6 month incident sequelae including diagnoses medication use and laboratory abnormalities in patients with COVID 19 who survived for at least 30 days after diagnosis We show that beyond the first 30 days of illness people with COVID 19 exhibit a higher risk of death and use of health resources Our high dimensional approach identifies incident sequelae in the respiratory system as well as several other sequelae that include nervous system and neurocognitive disorders mental health disorders metabolic disorders cardiovascular disorders gastrointestinal disorders malaise fatigue musculoskeletal pain and anaemia We show increased incident use of several therapeutic agents including pain medications opioids and non opioids as well as antidepressant anxiolytic antihypertensive and oral hypoglycaemic agents as well as evidence of laboratory abnormalities in several organ systems Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID 19 infection that is whether patients were not hospitalized hospitalized or admitted to intensive care Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID 19 These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID 19 1 |
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575 Review article gastrointestinal features in COVID 19 and the possibility of faecal transmission There is little published evidence on the gastrointestinal features of COVID 19 To report on the gastrointestinal manifestations and pathological findings of patients with COVID 19 and to discuss the possibility of faecal transmission We have reviewed gastrointestinal features of and faecal test results in COVID 19 from case reports and retrospective clinical studies relating to the digestive system published since the outbreak With an incidence of 3 1 41 79 159 201 gastrointestinal symptoms of COVID 19 included anorexia 39 9 55 138 50 2 101 201 diarrhoea 2 2 99 49 5 146 295 vomiting 3 6 5 138 66 7 4 6 nausea 1 1 99 29 4 59 201 abdominal pain 2 2 3 138 6 0 12 201 and gastrointestinal bleeding 4 2 52 13 7 10 73 Diarrhoea was the most common gastrointestinal symptom in children and adults with a mean duration of 4 1 2 5 days and was observed before and after diagnosis Vomiting was more prominent in children About 3 6 5 138 15 9 32 201 of adult and 6 5 2 31 66 7 4 6 of children patients presented vomiting Adult and children patients can present with digestive symptoms in the absence of respiratory symptoms The incidence of digestive manifestations was higher in the later than in the early stage of the epidemic but no differences in digestive symptoms among different regions were found Among the group of patients with a higher proportion of severe cases the proportion of gastrointestinal symptoms in severe patients was higher than that in nonsevere patients anorexia 66 7 vs 30 4 abdominal pain 8 3 vs 0 while in the group of patients with a lower severe rate the proportion with gastrointestinal symptoms was similar in severe and nonsevere cases nausea and vomiting 6 9 vs 4 6 diarrhoea 5 8 vs 3 5 Angiotensin converting enzyme 2 and virus nucleocapsid protein were detected in gastrointestinal epithelial cells and infectious virus particles were isolated from faeces Faecal PCR testing was as accurate as respiratory specimen PCR detection In 36 5 14 53 39 73 faecal PCR became positive 2 5 days later than sputum PCR positive Faecal excretion persisted after sputum excretion in 23 17 73 82 54 66 patients for 1 11 days Gastrointestinal symptoms are common in patients with COVID 19 and had an increased prevalence in the later stage of the recent epidemic in China SARS CoV 2 enters gastrointestinal epithelial cells and the faeces of COVID 19 patients are potentially infectious 0 |
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92 Post viral effects of COVID 19 in the olfactory system and their implications The mechanisms by which any upper respiratory virus including SARS CoV 2 impairs chemosensory function are not known COVID 19 is frequently associated with olfactory dysfunction after viral infection which provides a research opportunity to evaluate the natural course of this neurological finding Clinical trials and prospective and histological studies of new onset post viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples Although data from neuropathological specimens are now available neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge The active replication of SARS CoV 2 within the brain parenchyma ie in neurons and glia has not been proven Nevertheless post viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID 19 Evidence is also sparse for a direct causal relation between SARS CoV 2 infection and abnormal brain findings at autopsy and for trans synaptic spread of the virus from the olfactory epithelium to the olfactory bulb Taken together clinical radiological histological ultrastructural and molecular data implicate inflammation with or without infection in either the olfactory epithelium the olfactory bulb or both This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID 19 Neuroimaging has revealed localised inflammation in intracranial olfactory structures To date histopathological ultrastructural and molecular evidence does not suggest that SARS CoV 2 is an obligate neuropathogen WHERE NEXT The prevalence of CNS and olfactory bulb pathosis in patients with COVID 19 is not known We postulate that in people who have recovered from COVID 19 a chronic recrudescent or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease Persistent olfactory impairment with or without perceptual distortions ie parosmias or phantosmias after SARS CoV 2 infection could therefore serve as a marker to identify people with an increased long term risk of neurological disease 1 |
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116 Post Discharge Health Status and Symptoms in Patients with Severe COVID 19 Little is known about long term recovery from severe COVID 19 disease Here we characterize overall health physical health and mental health of patients 1 month after discharge for severe COVID 19 This was a prospective single health system observational cohort study of patients 18 years hospitalized with laboratory confirmed COVID 19 disease who required at least 6 l of oxygen during admission had intact baseline cognitive and functional status and were discharged alive Participants were enrolled between 30 and 40 days after discharge Outcomes were elicited through validated survey instruments the PROMIS Dyspnea Characteristics and PROMIS Global Health 10 A total of 161 patients 40 6 of eligible were enrolled 152 38 3 completed the survey Median age was 62 years interquartile range IQR 50 67 57 37 were female Overall 113 152 74 participants reported shortness of breath within the prior week median score 3 out of 10 IQR 0 5 vs 47 152 31 pre COVID 19 infection 0 IQR 0 1 p 0 001 Participants also rated their physical health and mental health as worse in their post COVID state 43 8 standard deviation 9 3 mental health 47 3 SD 9 3 compared to their pre COVID state 54 3 SD 9 3 54 3 SD 7 8 respectively both p 0 001 Physical and mental health means in the general US population are 50 SD 10 A total of 52 148 35 1 patients without pre COVID oxygen requirements needed home oxygen after hospital discharge 20 148 13 5 reported still using oxygen at time of survey Patients with severe COVID 19 disease typically experience sequelae affecting their respiratory status physical health and mental health for at least several weeks after hospital discharge 1 |
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55 Long COVID and Post COVID Health Complications An Up to Date Review on Clinical Conditions and Their Possible Molecular Mechanisms The COVID 19 pandemic has infected millions worldwide leaving a global burden for long term care of COVID 19 survivors It is thus imperative to study post COVID i e short term and long COVID i e long term effects specifically as local and systemic pathophysiological outcomes of other coronavirus related diseases such as Middle East Respiratory Syndrome MERS and Severe Acute Respiratory Syndrome SARS were well cataloged We conducted a comprehensive review of adverse post COVID health outcomes and potential long COVID effects We observed that such adverse outcomes were not localized Rather they affected different human systems including i immune system e g Guillain Barré syndrome rheumatoid arthritis pediatric inflammatory multisystem syndromes such as Kawasaki disease ii hematological system vascular hemostasis blood coagulation iii pulmonary system respiratory failure pulmonary thromboembolism pulmonary embolism pneumonia pulmonary vascular damage pulmonary fibrosis iv cardiovascular system myocardial hypertrophy coronary artery atherosclerosis focal myocardial fibrosis acute myocardial infarction cardiac hypertrophy v gastrointestinal hepatic and renal systems diarrhea nausea vomiting abdominal pain anorexia acid reflux gastrointestinal hemorrhage lack of appetite constipation vi skeletomuscular system immune mediated skin diseases psoriasis lupus vii nervous system loss of taste smell hearing headaches spasms convulsions confusion visual impairment nerve pain dizziness impaired consciousness nausea vomiting hemiplegia ataxia stroke cerebral hemorrhage viii mental health stress depression and anxiety We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes symptoms Overall the COVID 19 pathology is still characterized by cytokine storm that results to endothelial inflammation microvascular thrombosis and multiple organ failures 1 |
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488 Addressing Pediatric Mental Health Using Telehealth During Coronavirus Disease 2019 and Beyond A Narrative Review The pediatrician serves as a frontline provider addressing patients medical and mental health needs yet coronavirus disease 2019 COVID 19 is reshaping the way physicians deliver care Pediatricians are increasingly faced with the challenge of delivering care including mental health care remotely Given the rapidly evolving literature we performed a narrative review of the use of telehealth for mental health care for pediatric populations during the COVID 19 pandemic Areas of focus included 1 pediatric primary care settings 2 special pediatric populations eg eating disorders autism 3 access and engagement in telehealth care and 4 training opportunities available for mental health providers Themes that emerged across studies included the importance of meeting patients needs eg access to technological resources to optimize success in using telehealth tools and challenges around provider access to support tools for use during telehealth Thus we provided a summary of evidence based tools including COVID 19 specific resources for improving the remote delivery of mental health care by pediatricians We also reviewed future directions including trials currently underway to enhance understanding of future telehealth applications for pediatric mental health care 0 |
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271 Molecular Mechanisms of Muscle Fatigue Muscle fatigue MF declines the capacity of muscles to complete a task over time at a constant load MF is usually short lasting reversible and is experienced as a feeling of tiredness or lack of energy The leading causes of short lasting fatigue are related to overtraining undertraining deconditioning or physical injury Conversely MF can be persistent and more serious when associated with pathological states or following chronic exposure to certain medication or toxic composites In conjunction with chronic fatigue the muscle feels floppy and the force generated by muscles is always low causing the individual to feel frail constantly The leading cause underpinning the development of chronic fatigue is related to muscle wasting mediated by aging immobilization insulin resistance through high fat dietary intake or pharmacologically mediated Peroxisome Proliferator Activated Receptor PPAR agonism diseases associated with systemic inflammation arthritis sepsis infections trauma cardiovascular and respiratory disorders heart failure chronic obstructive pulmonary disease COPD chronic kidney failure muscle dystrophies muscle myopathies multiple sclerosis and more recently coronavirus disease 2019 COVID 19 The primary outcome of displaying chronic muscle fatigue is a poor quality of life This type of fatigue represents a significant daily challenge for those affected and for the national health authorities through the financial burden attached to patient support Although the origin of chronic fatigue is multifactorial the MF in illness conditions is intrinsically linked to the occurrence of muscle loss The sequence of events leading to chronic fatigue can be schematically denoted as trigger genetic or pathological molecular outcome within the muscle cell muscle wasting loss of muscle function occurrence of chronic muscle fatigue The present review will only highlight and discuss current knowledge on the molecular mechanisms that contribute to the upregulation of muscle wasting thereby helping us understand how we could prevent or treat this debilitating condition 1 |
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31 Post COVID syndrome symptoms functional disability and clinical severity phenotypes in hospitalized and nonhospitalized individuals A cross sectional evaluation from a community COVID rehabilitation service There is currently limited information on clinical severity phenotypes of symptoms and functional disability in post coronavirus disease 2019 COVID Syndrome PCS A purposive sample of 370 PCS patients from a dedicated community COVID 19 rehabilitation service was assessed using the COVID 19 Yorkshire Rehabilitation Scale where each symptom or functional difficulty was scored on a 0 10 Likert scale and also compared with before infection Phenotypes based on symptom severity were extracted to identify any noticeable patterns The correlation between symptom severity functional disability and overall health was explored The mean age was 47 years with 237 64 females The median duration of symptoms was 211 days interquartile range 143 353 Symptoms and functional difficulties increased substantially when compared to before infection Three distinct severity phenotypes of mild n 90 moderate n 186 and severe n 94 were identified where the severity of individual symptoms was of similar severity within each phenotype Symptom scores were strongly positively correlated with functional difficulty scores 0 7 0 6 0 7 and moderately negatively correlated with overall health 0 4 0 3 to 0 5 This is the first study reporting on severity phenotypes in a largely nonhospitalized PCS cohort Severity phenotypes might help stratify patients for targeted interventions and planning of care pathways 1 |
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201 Post COVID 19 Symptom Burden What is Long COVID and How Should We Manage It The enduring impact of COVID 19 on patients has been examined in recent studies leading to the description of Long COVID We report the lasting symptom burden of COVID 19 patients from the first wave of the pandemic All patients with COVID 19 pneumonia discharged from a large teaching hospital trust were offered follow up We assessed symptom burden at follow up using a standardised data collection technique during virtual outpatient clinic appointments Eighty six percent of patients reported at least one residual symptom at follow up No patients had persistent radiographic abnormalities The presence of symptoms at follow up was not associated with the severity of the acute COVID 19 illness Females were significantly more likely to report residual symptoms including anxiety p 0 001 fatigue p 0 004 and myalgia p 0 022 The presence of long lasting symptoms is common in COVID 19 patients We suggest that the phenomenon of Long COVID may not be directly attributable to the effect of SARS CoV 2 and believe the biopsychosocial effects of COVID 19 may play a greater role in its aetiology 1 |
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421 Venous Thromboembolism among Critically Ill Children A Narrative Review Venous thromboembolism VTE is a leading cause of morbidity and mortality among hospitalized patients including children In recent years it has become clear that hospitalization and critical illness bestow an increased VTE risk in pediatrics and relate to mortality and life limiting comorbidities For critically ill children reported rates of VTE vary by study sampling techniques presence of inherited or acquired thrombophilia acute and chronic immobility underlying illness prompting hospitalization and clinical factors related to illness severity such as central venous catheterization length of stay mechanical ventilation and patient age Accordingly critically ill children with new signs of venous congestion acute inflammation or unexplained acute organ dysfunction should be routinely evaluated for VTE This narrative review summarizes recent and historical literature regarding risk factors prevention presentation treatment and outcomes of VTE in critically ill children In addition we identify knowledge gaps and priorities for future collaborative research on this vital condition Special attention is given to the clinical trial opportunities challenges and ongoing efforts in thromboprophylaxis in critically ill children including those hospitalized for disease related to novel coronavirus COVID 19 and multisystem inflammatory disease in children 0 |
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648 Virus triggered secondary hemophagocytic lymphohistiocytosis Primary familial hereditary and secondary non familial hereditary hemophagocytic lymphohistiocytosis HLH are hyperinflammatory and hypercytokinemic syndromes Secondary HLH includes infection eg viral bacterial fungal parasitic and non infection eg collagen disease or malignancy related diseases Viral HLH is the major type among all age groups Secondary viral HLH and primary HLH must be differentiated carefully because primary HLH can be associated with viral infection s and the outcome is dismal without a timely diagnosis and hematopoietic stem cell transplantation HSCT Epstein Barr virus EBV related HLH EBV HLH is the most common type of viral HLH in childhood For non EBV HLH appropriate treatment of viral infection followed by immunomodulatory agent s such as corticosteroids intravenous immunoglobulin or cyclosporine A is usually successful however recent SARS CoV 2 related HLH may become life threatening EBV HLH may occur heterogeneously associated with the primary infection with chronic active EBV infection or with underlying primary HLH Although immunomodulatory agent s are effective in the majority of EBV HLH cases management differs from that of non EBV HLH because severe and refractory cases may require etoposide containing HLH 1994 2004 regimens or other experimental agents The novel agent emapalumab an anti IFN γ monoclonal antibody can be used to treat EBV HLH cases to avoid the risk of secondary malignancy due to etoposide Finally HSCT is required for refractory EBV HLH cases and can also be curative in some other cases 0 |
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450 Emerging Needs and Viability of Telepsychiatry During and Post COVID 19 Era A Literature Review The coronavirus disease 2019 COVID 19 pandemic has resulted in nationwide stay at home orders in an effort to slow the spread severely impacting the healthcare sector Telepsychiatry provides a platform bridging the gap through advanced technologies connecting mental health providers and patients who need their services overcoming previous barriers of great distances lack of transportation and even time constraints The most obvious benefit is increased accessibility to mental healthcare especially in underserved and remote areas where there is no easy access for in person care It is important to note that benefits are not limited to patients but also allow clinicians greater flexibility in scheduling and reduced practice overhead costs both of which aid with physician burnout and burden Telepsychiatry during COVID 19 provides its own unique advantages over in person visits The risk of exposure to healthcare workers and patients receiving care is reduced allowing immunocompromised patients to receive much needed psychiatric care Without the need to meet in person self isolating psychiatrists can still provide care decreasing strain on their co workers Although telepsychiatry is relatively new it has already exhibited considerable success in its effectiveness at treating psychiatric conditions and widespread corollary benefits Telepsychiatric consults may be carried out synchronously and asynchronously each having benefits and setbacks Different mobile application interventions have been explored which are available for the purpose of both monitoring assessing patients and or providing treatment The scope of conditions these applications address is broad from anxiety disorders to schizophrenia to depression As promising and beneficial telepsychiatry may seem it is necessary to recognize that building the program can be challenging It involves adapting to new methods in medicine We highlighted barriers to general telepsychiatry the most prominent being technological literacy of both physician and patient and possible negative effects of eliminating the in person patient doctor interaction 0 |
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365 Indoor air quality at school and students performance Recommendations of the UNESCO Chair on Health Education and Sustainable Development the Italian Society of Environmental Medicine SIMA The issue of indoor air quality IAQ concerns 64 million students across Europe but it is still a neglected topic although it impacts both their health and learning outcomes Classroommicroclimate is the first key factor determining a healthy or unhealthy school environment and it is influenced by ventilation temperature and humidity rate Classrooms are usually crowded overheated and poorly ventilated thus resulting in possible increases of carbon dioxide CO sub 2 sub that can cause several problems when its concentrations exceed the value of 0 15 percentage volume of CO sub 2 sub 1500 ppm or even at lower levels 1000 ppm CO sub 2 sub can also arise from outside the school being widely produced by the combustion of fossils or road traffic Anthropogenic activities are responsible for the emission of nitrogen dioxide NO sub 2 sub and polycyclic aromatic hydrocarbons PAH too which represent other possible external contaminants potentially impairing IAQ Furtherdangerous exposures for students health are those related to natural emission of gas Radon which typically accumulates in poorly ventilated classrooms and volatile organic compounds VOCs released by building materials paints furnishings detergents while chemicals substances i e cyanoacrylate lead cadmium nickel might be contained in school materials Finally particulate matter PM2 5 and PM10 originating from road traffic domestic heating or industrial activities represent additional possible contaminants impacting schools air quality Poor IAQ might result in mild adverse events i e headaches nausea etc or cause respiratory problems More frequently IAQ affects students attention and their school performances as widely documented by many studies Standardized tests administered to pupils exposed to poor IAQ to assess reading and mathematical abilities systematically result in worse outcomes compared to students staying in healthy classroom environments In this paper we present recommendations of UNESCO Chair on Health Education and Sustainable Development and Italian Society of Environmental Medicine SIMA to ensure an optimal IAQ at school including some post COVID 19 issues 0 |
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400 COVID 19 Vaccine Concerns Fact or Fiction One year has elapsed since a team of Chinese scientists reported the first case of COVID 19 in Wuhan China on January 8 2020 after sequencing the first viral genetic material Since then many vaccines were rushed into testing bypassing animal experimentations with more than 200 pharma companies in different countries declaring the development of different vaccines each with their own strategy for generating immunity despite the arguments of many infectious disease experts that 18 months for a first vaccine is an incredibly aggressive schedule because it takes an average of 10 years to develop a vaccine Ten vaccine candidates have already entered phase 3 clinical trials in humans These vaccines rely on different types of technology the most innovative of which use the genetic material messenger RNA Many provocative questions and genuine concerns have been raised such as short durations of efficacy and safety follow ups lack of identified correlates of protection morbidity and mortality cases reported shortly after vaccination uncertainties regarding the risk of enhanced disease on exposure to the virus in the long term the possibility of viral transmission after vaccination the reported reduced efficacies of these vaccines against new variants the efficacy and safety of these vaccines in the previously excluded subgroups such as children pregnant women the frail elderly high risk population and immunocompromised individuals the unknown risk of immunogenicity induced autoimmune diseases cancer and chronic inflammation the risk of genome transformation mainly in the presence of reverse transcriptase and finally the potential coercion that may be imposed by either public or private sectors on citizens to receive the vaccine Many plausible questions are apparent with no clear and convincing answers 0 |
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517 Severe Acute Respiratory Syndrome Coronavirus 2 SARS CoV 2 Setting specific Transmission Rates A Systematic Review and Meta analysis Understanding the drivers of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 transmission is crucial for control policies but evidence of transmission rates in different settings remains limited We conducted a systematic review to estimate secondary attack rates SARs and observed reproduction numbers Robs in different settings exploring differences by age symptom status and duration of exposure To account for additional study heterogeneity we employed a beta binomial model to pool SARs across studies and a negative binomial model to estimate Robs Households showed the highest transmission rates with a pooled SAR of 21 1 95 confidence interval CI 17 4 24 8 SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of 5 days SARs related to contacts at social events with family and friends were higher than those for low risk casual contacts 5 9 vs 1 2 Estimates of SARs and Robs for asymptomatic index cases were approximately one seventh and for presymptomatic two thirds of those for symptomatic index cases We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context which is more limited when examining all settings Our results suggest that exposure in settings with familiar contacts increases SARS CoV 2 transmission potential Additionally the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies such as contact tracing testing and rapid isolation of cases There were limited data to explore transmission patterns in workplaces schools and care homes highlighting the need for further research in such settings 0 |
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145 Patients Experiences of Long COVID in the Community and Recommendations for Improving Services A Quality Improvement Survey Long COVID is a multisystem disease that lasts for 4 or more weeks following initial symptoms of COVID 19 In the UK at least 10 of patient report symptoms at 12 weeks following a positive COVID 19 test The aims of this quality improvement survey were to explore patients acute and post acute long COVID 19 symptoms their experiences of community services and their recommendations for improving these services Seventy patients diagnosed with COVID were randomly selected from 2 large socially and ethnically diverse primary care practices Of those contactable by telephone 85 41 48 agreed to participate in the quality improvement survey They were interviewed by telephone using a semi structured questionnaire about community services for COVID 19 patients Interviews lasted 10 to 15 minutes Forty nine percent of patients reported at least 1 post acute COVID 19 symptom The most common were severe fatigue 45 breathlessness 30 neurocognitive difficulties such as poor memory poor concentration and brain fog 30 headaches 20 and joint pain 20 Many patients felt isolated and fearful with scant information about community resources and little safety netting advice Patients also expected more from primary care with over half 56 recommending regular phone calls and follow up from healthcare staff as the most important approach in their recovery In line with patients requests for more support the practices now routinely refer patients with long COVID to an on site social prescriber who explores how they are getting on refers them to the GP or practice nurse when required and sign posts them to support services in the community 1 |
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255 Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalitis Following COVID 19 Systematic Review and Meta synthesis Since the onset of the COVID 19 pandemic a growing number of reports have described cases of acute disseminated encephalomyelitis ADEM and acute hemorrhagic leukoencephalitis AHLE following infection with COVID 19 Given their relatively rare occurrence the primary objective of this systematic review was to synthesize their clinical features response to treatments and clinical outcomes to better understand the nature of this neurologic consequence of COVID 19 infection Patients with a history of COVID 19 infection were included if their reports provided adequate detail to confirm a diagnosis of ADEM or AHLE by virtue of clinical features radiographic abnormalities and histopathologic findings Cases purported to be secondary to vaccination against COVID 19 or occurring in the context of a preexisting relapsing CNS demyelinating disease were excluded Case reports and series were identified via PubMed on May 17 2021 and 4 additional cases from the authors hospital files supplemented the systematic review of the literature Summary statistics were used to describe variables using a complete case analysis approach Forty six patients 28 men median age 49 5 years 1 3 50 years old were analyzed derived from 26 case reports or series originating from 8 countries alongside 4 patient cases from the authors hospital files COVID 19 infection was laboratory confirmed in 91 of cases and infection severity necessitated intensive care in 67 ADEM occurred in 31 cases whereas AHLE occurred in 15 with a median presenting nadir modified Rankin Scale score of 5 bedridden Anti MOG seropositivity was rare 1 15 patients tested Noninflammatory CSF was present in 30 Hemorrhage on brain MRI was identified in 42 Seventy percent received immunomodulatory treatments most commonly steroids IV immunoglobulins or plasmapheresis The final mRS score was 4 in 64 of patients with adequate follow up information including 32 who died In contrast to ADEM cases from the prepandemic era reported post COVID 19 ADEM and AHLE cases were often advanced in age at onset experienced severe antecedent infection displayed an unusually high rate of hemorrhage on neuroimaging and routinely had poor neurologic outcomes including a high mortality rate Findings are limited by nonstandardized reporting of cases truncated follow up information and presumed publication bias 1 |
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467 Inflammation and kidney involvement in human viral diseases caused by SARS CoV 2 HIV HCV and HBV Inflammation is closely related to renal diseases This is particularly true for renal diseases caused by infections as in viral diseases In this review we highlight the inflammatory mechanisms that underlie kidney dysfunction in SARS CoV 2 human immunodeficiency HIV hepatitis C HCV and hepatitis B HBV infections The pathophysiology of renal involvement in COVID 19 is complex but kidney damage is frequent and the prognosis is worse when it happens Virus like particles were demonstrated mostly in renal tubular epithelial cells and podocytes which suggest that SARS CoV 2 directly affects the kidneys SARS CoV 2 uses the angiotensin converting enzyme 2 receptor which is found in endothelial cells to infect the human host cells Critical patients with SARS CoV 2 associated acute kidney injury AKI show an increase in inflammatory cytokines IL 1β IL 8 IFN γ TNF α known as cytokine storm that favors renal dysfunction by causing intrarenal inflammation increased vascular permeability volume depletion thromboembolic events in microvasculature and persistent local inflammation Besides AKI SARS CoV 2 can also cause glomerular disease as other viral infections such as in HIV HBV and HCV HIV infected patients present chronic inflammation that can lead to a number of renal diseases Proinflammatory cytokines and TNF induced apoptosis are some of the underlying mechanisms that may explain the virus induced renal diseases that are here reviewed 0 |
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231 Post COVID lung fibrosis The tsunami that will follow the earthquake The SARS CoV 2 pandemic has already infected in excess of 50 million people worldwide and resulted in 1 2 million deaths While the majority of those infected will not have long term pulmonary sequelae 5 10 will develop severe COVID 19 pneumonia and acute respiratory distress syndrome ARDS The natural history of these severely affected patients is unclear at present but using our knowledge of closely related coronavirus outbreaks like severe acute respiratory distress syndrome SARS and middle east respiratory syndrome MERS we would hypothesize that the majority will stabilize or improve over time although some patients will progress to advanced lung fibrosis or post COVID interstitial lung disease PC ILD Unlike the SARS and MERS outbreaks which affected only a few thousands the sheer scale of the present pandemic suggests that physicians are likely to encounter large numbers of patients potentially hundreds of thousands with PC ILD In this review we discuss the pathogenesis natural history and radiology of such patients and touch on clinical laboratory and radiographic clues at presentation which might help predict the future development of lung fibrosis Finally we discuss the responsible use of antifibrotic drugs such as pirfenidone nintedanib and some newer antifibrotics still in the pipeline The biological rationale of these drugs and the patient groups where they may have a plausible role will be discussed We conclude by stressing the importance of careful longitudinal follow up of multiple cohorts of post COVID survivors with serial lung function and imaging This will eventually help to determine the natural history course and response to therapy of these patients 1 |
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308 Acute and Chronic Effects of COVID 19 on the Cardiovascular System COVID 19 has shown significant morbidity with the involvement of multiple systems including the cardiovascular system Cardiovascular manifestations in the acute phase can include myocardial injury itself myocardial infarction venous thromboembolic events myocarditis Takotsubo syndrome and different arrhythmic events Myocardial injury defined by the rise of cardiac biomarkers in blood has been found in multiple studies with a prevalence of about 20 Its presence is related to worse clinical outcomes and in hospital mortality The mechanisms of myocardial injury have been the subject of intense research but still need to be clarified The characterization of the cardiac affectation with echocardiography and cardiac magnetic resonance has found mixed results in different studies with a striking incidence of imaging criteria for myocarditis Regarding post acute and chronic follow up results the persistence of symptoms and imaging changes in recovered COVID 19 patients has raised concerns about the duration and the possible significance of these findings Even though the knowledge about this disease has increased incredibly in the last year many aspects are still unclear and warrant further research 1 |
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44 COVID 19 in children SARS CoV 2 related inflammatory multisystem syndrome mimicking Kawasaki disease SARS CoV 2 pandemics is characterized by a high level of infectivity and a high mortality among adults at risk older than 65 years obesity diabetes systemic hypertension Following a common viral pneumonia a multisystem inflammatory syndrome sometimes occurs including an Acute Respiratory Distress Syndrome ARDS carrying a high mortality Unlike most common respiratory viruses children seem less susceptible to SARS CoV 2 infection and generally develop a mild disease with low mortality However clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes vasopressors and volume loading have been recently described Both clinical symptoms i e high and persistent fever gastrointestinal disorders skin rash conjunctivitis and dry cracked lips and biological signs e g elevated CRP PCT hyperferritinemia resembled Kawasaki disease In most instances intravenous immunoglobin therapy improved the cardiac function and led to full recovery within a few days However adjunctive steroid therapy and sometimes biotherapy e g anti IL 1Ra anti IL 6 monoclonal antibodies were often necessary Although almost all children fully recovered within a week some of them developed coronary artery dilation or aneurysm Thus a new Multisystem Inflammatory Syndrome associated with SARS CoV 2 has been recently described in children and helps to better understand Kawasaki disease pathophysiology 1 |
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564 Defining Nonadherence and Nonpersistence to Anti Vascular Endothelial Growth Factor Therapies in Neovascular Age Related Macular Degeneration Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice real world outcomes to intravitreal injection therapy in patients with neovascular age related macular degeneration nAMD Currently there is a lack of consensus on the definition and classification of adherence specific to this context To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti vascular endothelial growth factor therapy Following a systematic review of currently used terminology in the literature a subcommittee panel of retinal experts developed a set of definitions and classification for validation Definitions were restricted to use in patients with nAMD requiring intravitreal anti vascular endothelial growth factor therapy Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach with predetermined mean scores of 7 5 or more signifying consensus Subsequent endorsement of the definitions was provided from a second set of retinal experts with more than 50 members agreeing or strongly agreeing with all definitions Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months with a visit considered missed if it exceeded more than 2 weeks from the recommended date Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months The additional terms planned discontinuation and transfer of care were also established Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions 1 patient associated 2 condition associated 3 therapy associated 4 health system and health care team associated 5 social economic and 6 other with subcategories specific to treatment for nAMD This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti vascular endothelial growth factor treatments This may have additional importance given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD 0 |
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394 Biofilms and Coronavirus Reservoirs a Perspective Review Bats are a key reservoir of coronaviruses CoVs including the agent of the severe acute respiratory syndrome SARS CoV 2 responsible for the recent deadly viral pneumonia pandemic However understanding how bats can harbor several microorganisms without developing illnesses is still a matter under discussion Viruses and other pathogens are often studied as stand alone entities despite that in nature they mostly live in multispecies associations called biofilms both externally and within the host Microorganisms in biofilms are enclosed by an extracellular matrix that confers protection and improves survival Previous studies have shown that viruses can secondarily colonize preexisting biofilms and viral biofilms have also been described In this review we raise the perspective that CoVs can persistently infect bats due to their association with biofilm structures This phenomenon potentially provides an optimal environment for nonpathogenic and well adapted viruses to interact with the host as well as for viral recombination Biofilms can also enhance virion viability in extracellular environments such as on fomites and in aquatic sediments allowing viral persistence and dissemination Moreover understanding the biofilm lifestyle of CoVs in reservoirs might contribute to explaining several burning questions as to persistence and transmissibility of highly pathogenic emerging CoVs 0 |
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262 Long COVID in Patients With Mild to Moderate Disease Do Thyroid Function and Autoimmunity Play a Role Post acute sequelae of coronavirus disease 2019 COVID 19 or long COVID LC is an emerging global health issue Fatigue is a common feature Whether thyroid function and autoimmunity play a role is uncertain We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC We included consecutive adults without a known thyroid disorder who were admitted to a major COVID 19 center for confirmed COVID 19 from July to December 2020 Thyroid function tests and antithyroid antibodies were measured for all patients on admission and at follow up LC was defined by the presence or persistence of symptoms upon follow up In total 204 patients median age 55 0 years 95 men 46 6 were reassessed at a median of 89 days interquartile range 69 99 after acute COVID 19 Of the 204 patients 41 20 1 had LC Female sex adjusted odds ratio 2 48 P 018 and severe acute respiratory syndrome coronavirus 2 polymerase chain reaction cycle threshold value of 25 on admission adjusted odds ratio 2 84 P 012 independently predicted the occurrence of LC Upon follow up most abnormal thyroid function tests in acute COVID 19 resolved and incident thyroid dysfunction was rare Nonetheless we observed incident antithyroid peroxidase anti TPO positivity Although baseline or follow up thyroid function tests were not associated with the occurrence of LC among 172 patients with symptomatic acute COVID 19 symptom resolution was more likely in those with positive anti TPO upon follow up P 043 LC is common among COVID 19 survivors with females and those with higher viral load in acute COVID 19 particularly being vulnerable The observation of incident anti TPO positivity warrants further follow up for thyroid dysfunction Whether anti TPO plays a protective role in LC remains to be elucidated 1 |
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19 A Review of Persistent Post COVID Syndrome PPCS Persistent post COVID syndrome also referred to as long COVID is a pathologic entity which involves persistent physical medical and cognitive sequelae following COVID 19 including persistent immunosuppression as well as pulmonary cardiac and vascular fibrosis Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life Inhibiting transforming growth factor beta TGF β an immuno and a fibrosis modulator may attenuate these post COVID sequelae Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID 19 and its presymptomatic and prodromal periods by comparison the postdrome which occurs in the aftermath of COVID 19 which we refer to as persistent post COVID syndrome has received little attention Potential long term effects from post COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital placing a burden on healthcare systems patients families and society in general to care for these medically devastated COVID 19 survivors This review explores underlying mechanisms and possible manifestations of persistent post COVID syndrome and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post COVID syndrome 1 |
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240 Population Based Estimates of Post acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 SARS CoV 2 Infection PASC Prevalence and Characteristics Emerging evidence suggests many people have persistent symptoms after acute coronavirus disease 2019 COVID 19 illness Our objective was to estimate the prevalence and correlates of post acute sequelae of severe acute respiratory syndrome coronavirus 2 SARS CoV 2 infection PASC We used a population based probability survey of adults with COVID 19 in Michigan Living noninstitutionalized adults aged 18 in the Michigan Disease Surveillance System with COVID 19 onset through mid April 2020 were eligible for selection N 28 000 Among 2000 selected 629 completed the survey between June December 2020 We estimated PASC prevalence defined as persistent symptoms 30 30 day COVID 19 or 60 60 day COVID 19 days post COVID 19 onset overall and by sociodemographic and clinical factors We used modified Poisson regression to produce adjusted prevalence ratios aPRs for potential risk factors The analytic sample n 593 was predominantly female 56 1 aged 45 years 68 2 and non Hispanic White 46 3 or Black 34 8 Thirty and 60 day COVID 19 were highly prevalent 52 5 and 35 0 even among nonhospitalized respondents 43 7 and 26 9 and respondents reporting mild symptoms 29 2 and 24 5 Respondents reporting very severe vs mild symptoms had 2 25 times higher prevalence of 30 day COVID 19 aPR 2 25 95 CI 1 46 3 46 and 1 71 times higher prevalence of 60 day COVID 19 aPR 1 71 95 CI 1 02 2 88 Hospitalized vs nonhospitalized respondents had 40 higher prevalence of both 30 day aPR 1 37 95 CI 1 12 1 69 and 60 day aPR 1 40 95 CI 1 02 1 93 COVID 19 PASC is highly prevalent among cases reporting severe initial symptoms and to a lesser extent cases reporting mild and moderate symptoms 1 |
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529 Challenges for Child Mental Health Raised by School Closure and Home Confinement During the COVID 19 Pandemic The closure of schools during the COVID 19 pandemic has interrupted the education of children worldwide This paper reviews the psychological effects of this action on children and the impact on school based services Emerging epidemiologic findings have generated an intense debate about the need for and potential benefit of school closure in the context of COVID 19 International research reveals reactions in children that are not typically considered in the disaster literature as well as those that arise in other disasters School closure also has curtailed the delivery of mental health services commonly offered in schools The debate about school closure will likely persist depending on local disease conditions and school readiness Moreover school closure is a possibility in future epidemics and pandemics and other disasters The benefit of school closure must be balanced against the risk to childrens education and psychosocial development 0 |
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185 The impact of COVID 19 critical illness on new disability functional outcomes and return to work at 6 months a prospective cohort study There are few reports of new functional impairment following critical illness from COVID 19 We aimed to describe the incidence of death or new disability functional impairment and changes in health related quality of life of patients after COVID 19 critical illness at 6 months In a nationally representative multicenter prospective cohort study of COVID 19 critical illness we determined the prevalence of death or new disability at 6 months the primary outcome We measured mortality new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2 0 12L WHODAS and health status with the EQ5D 5L sup TM sup Of 274 eligible patients 212 were enrolled from 30 hospitals The median age was 61 51 70 years and 124 58 5 patients were male At 6 months 43 160 26 9 patients died and 42 108 38 9 responding survivors reported new disability Compared to pre illness the WHODAS percentage score worsened mean difference MD 10 40 95 CI 7 06 13 77 p 0 001 Thirteen 11 4 survivors had not returned to work due to poor health There was a decrease in the EQ 5D 5L sup TM sup utility score MD 0 19 0 28 to 0 10 p 0 001 At 6 months 82 of 115 71 3 patients reported persistent symptoms The independent predictors of death or new disability were higher severity of illness and increased frailty At six months after COVID 19 critical illness death and new disability was substantial Over a third of survivors had new disability which was widespread across all areas of functioning Clinical trial registration NCT04401254 May 26 2020 1 |
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41 Post COVID 19 global health strategies the need for an interdisciplinary approach For survivors of severe COVID 19 disease having defeated the virus is just the beginning of an uncharted recovery path What follows after the acute phase of SARS CoV 2 infection depends on the extension and severity of viral attacks in different cell types and organs Despite the ridiculously large number of papers that have flooded scientific journals and preprint hosting websites a clear clinical picture of COVID 19 aftermath is vague at best Without larger prospective observational studies that are only now being started clinicians can retrieve information just from case reports and or small studies This is the time to understand how COVID 19 goes forward and what consequences survivors may expect to experience To this aim a multidisciplinary post acute care service involving several specialists has been established at the Fondazione Policlinico Universitario A Gemelli IRCSS Rome Italy Although COVID 19 is an infectious disease primarily affecting the lung its multi organ involvement requires an interdisciplinary approach encompassing virtually all branches of internal medicine and geriatrics In particular during the post acute phase the geriatrician may serve as the case manager of a multidisciplinary team The aim of this article is to describe the importance of the interdisciplinary approach coordinated by geriatrician to cope the potential post acute care needs of recovered COVID 19 patients 1 |
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516 Scaling up COVID 19 rapid antigen tests promises and challenges WHO recommends a minimum of 80 sensitivity and 97 specificity for antigen detection rapid diagnostic tests Ag RDTs which can be used for patients with symptoms consistent with COVID 19 However after the acute phase when viral load decreases use of Ag RDTs might lead to high rates of false negatives suggesting that the tests should be replaced by a combination of molecular and serological tests When the likelihood of having COVID 19 is low such as for asymptomatic individuals in low prevalence settings for travel return to schools workplaces and mass gatherings Ag RDTs with high negative predictive values can be used with confidence to rule out infection For those who test positive in low prevalence settings the high false positive rate means that mitigation strategies such as molecular testing to confirm positive results are needed Ag RDTs when used appropriately are promising tools for scaling up testing and ensuring that patient management and public health measures can be implemented without delay 0 |
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622 Clinical outcomes among hospitalized US adults with asthma or chronic obstructive pulmonary disease with or without COVID 19 b Objective b This study assesses the risk of severe clinical outcomes during hospitalizations of adults with asthma and or COPD plus COVID 19 and compares those risks with those during hospitalizations of adults with asthma and or COPD without COVID 19 b Methods b We used data from 877 U S hospitals from the Premier Healthcare Database during March 2020 March 2021 Hospitalizations n 311 215 among patients aged 18 years with an ICD 10 CM diagnosis involving asthma or COPD were classified into three groups adults with asthma but not COPD adults with COPD but not asthma and adults with both asthma and COPD We used multivariable Poisson regression to assess associations of severe clinical outcomes intensive care unit ICU admission use of invasive mechanical ventilation IMV and death and COVID 19 status b Results b The percentage of hospitalizations among patients with asthma and COVID 19 resulting in ICU admission IMV and death were 46 9 14 0 and 8 0 respectively These risks were higher than those among patients with asthma without COVID 19 adjusted risk ratio aRR 1 17 95 confidence interval CI 1 14 1 21 1 61 95 CI 1 50 1 73 and 5 56 95 CI 4 89 6 32 respectively Risks of ICU admission IMV and death were also high among patients with COPD and COVID 19 and exceeded the corresponding risks among patients with COPD without COVID 19 b Conclusion b Hospitalizations among patients with asthma and or COPD with COVID 19 had a more severe clinical course than hospitalizations for asthma and or COPD exacerbations without COVID 19 0 |
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562 Combining Improvement and Implementation Sciences and Practices for the Post COVID 19 Era Health services made many changes quickly in response to the SARS CoV 2 pandemic Many more are being made Some changes were already evaluated and there are rigorous research methods and frameworks for evaluating their local implementation and effectiveness But how useful are these methods for evaluating changes where evidence of effectiveness is uncertain or which need adaptation in a rapidly changing situation Has implementation science provided implementers with tools for effective implementation of changes that need to be made quickly in response to the demands of the pandemic This perspectives article describes how parts of the research and practitioner communities can use and develop a combination of implementation and improvement to enable faster and more effective change in the future especially where evidence of local effectiveness is limited We draw on previous reviews about the advantages and disadvantages of combining these two domains of knowledge and practice We describe a generic digitally assisted rapid cycle testing DA RCT approach that combines elements of each in order to better describe a change monitor outcomes and make adjustments to the change when implemented in a dynamic environment 0 |
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545 Impact of lockdown on key workers findings from the COVID 19 survey in four UK national longitudinal studies Key workers played a pivotal role during the national lockdown in the UKs response to the COVID 19 pandemic Although protective measures have been taken the impact of the pandemic on key workers is yet to be fully elucidated Participants were from four longitudinal age homogeneous British cohorts born in 2001 1990 1970 and 1958 A web based survey provided outcome data during the first UK national lockdown May 2020 on COVID 19 infection status changes in financial situation trust in government conflict with people around household composition psychological distress alcohol consumption smoking and sleep duration Generalised linear models with logit link assessed the association between being a key worker and the above outcomes Adjustment was made for cohort design non response sex ethnicity adult socioeconomic position SEP childhood SEP the presence of a chronic illness and receipt of a shielding letter Meta analyses were performed across the cohorts 13 736 participants were included During lockdown being a key worker was associated with increased chances of being infected with COVID 19 OR 1 43 95 CI 1 22 to 1 68 and experiencing conflict with people around OR 1 19 95 CI 1 03 to 1 37 However key workers were less likely to be worse off financially OR 0 32 95 CI 0 24 to 0 65 to consume more alcohol OR 0 88 95 CI 0 79 to 0 98 or to smoke more OR 0 60 95 CI 0 44 to 0 80 during lockdown Interestingly being a key worker was not associated with psychological distress OR 0 95 95 CI 0 85 to 1 05 Being a key worker during the first UK COVID 19 lockdown was a double edged sword with both benefits and downsides The UK government had the basic duty to protect its key workers from SARS CoV 2 infection but it may have failed to do so and there is an urgent need to rectify this in light of the ongoing third wave 0 |
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112 Neurological Complications of COVID 19 in Children Neurological complications of coronavirus disease 2019 COVID 19 are highly variable and can be quite severe but they are rare in children A careful understanding of the variety of presentations of neurological symptoms related to COVID 19 is critical for the effective management of these patients Given the smaller numbers of children with these complications a comprehensive review of neurological presentations in adults with COVID 19 may help facilitate the understanding of those complications that may present in children and how these presentations may be similar b i Pediatr Ann i 2021 50 6 e259 e263 b 1 |
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346 Online alcohol sales and home delivery An international policy review and systematic literature review Online alcohol sales are experiencing rapid growth in many places accelerated by the COVID 19 pandemic prompting new laws and regulations There are no comprehensive and systematic analyses of the laws or their effectiveness To summarise international policies governing online alcohol sale and delivery including changes occurring with COVID 19 and examine available evidence of retailer compliance with such policies A policy review of 77 jurisdictions in six English speaking OECD countries United States Canada United Kingdom Ireland Australia and New Zealand We synthesised policies according to ten elements identified as potentially relevant for public health regulation A systematic literature review of compliance evaluations in Medline Medline Epub EMBASE CINAHL Web of Science and Google Scholar 72 of 77 jurisdictions permitted online alcohol sales and home delivery Few jurisdictions require age verification at the time of purchase n 7 but most require it at delivery n 71 Since the COVID 19 pandemic began most jurisdictions 69 have either temporarily or permanently relaxed liquor regulations for alcohol home delivery Three articles examined retailer compliance with age restrictions and found relatively low compliance 0 46 Many jurisdictions permit the online sale and delivery of alcohol but regulation of these sales varies widely In most regulations do not meet the same standard as bricks and mortar establishments and may be insufficient to prevent youth access 0 |
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232 The Present State of Understanding of Multisystem Inflammatory Syndrome in Children MIS C Associated with SARS CoV 2 Infection A Comprehensive Review of the Current Literature The coronavirus disease 2019 COVID 19 has as of Oct 14 2020 infected approximately 38 million people worldwide The most feared sequelae of COVID 19 in adults are severe often fatal lung disease venous thromboembolic disease cerebrovascular disease and multiple organ system failure Fortunately unlike adults most children who contract COVID 19 have a mild respiratory illness or asymptomatic It is now evident that a small percentage of children develop a critical and novel illness with persistent fever prominent GI symptoms single or multi organ dysfunction including shock and laboratory evidence of profound inflammation which has been termed multisystem inflammatory syndrome in children MIS C by the CDC Some of the reported cases share features with well known inflammatory syndromes such as Kawasaki disease macrophage activation syndrome hemophagocytic lymphohistiocytosis and toxic shock syndrome The temporal relationship of MIS C and COVID 19 suggests a post infectious immune dysregulation Patients with MIS C especially those with cardiac dysfunction and or shock should preferably be managed in pediatric intensive care We will discuss the epidemiology of MIS C similarities with known inflammatory syndromes in children clinical presentation and present management options 1 |
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74 Insights into SARS CoV 2 Persistence and Its Relevance Severe acute respiratory syndrome coronavirus 2 SARS CoV 2 the causative agent of coronavirus disease 2019 COVID 19 continues to wreak havoc threatening the public health services and imposing economic collapse worldwide Tailoring public health responses to the SARS CoV 2 pandemic depends on understanding the mechanism of viral replication disease pathogenesis accurately identifying acute infections and mapping the spreading risk of hotspots across the globe However effective identification and isolation of persons with asymptomatic and mild SARS CoV 2 infections remain the major obstacles to efforts in controlling the SARS CoV 2 spread and hence the pandemic Understanding the mechanism of persistent viral shedding reinfection and the post acute sequalae of SARS CoV 2 infection PASC is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors Here we present a living literature review January 2020 through 15 March 2021 on SARS CoV 2 viral persistence reinfection and PASC We also highlight potential areas of research to uncover putative links between viral persistence intra host evolution host immune status and protective immunity to guide and direct future basic science and clinical research priorities 1 |
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227 Frequency signs and symptoms and criteria adopted for long COVID 19 A systematic review To identify systematically evaluate and summarise the best available evidence on the frequency of long COVID 19 post acute COVID 19 syndrome its clinical manifestations and the criteria used for diagnosis Systematic review conducted with a comprehensive search including formal databases COVID 19 or SARS CoV 2 data sources grey literature and manual search We considered for inclusion clinical trials observational longitudinal comparative and non comparative studies cross sectional before and after and case series We assessed the methodological quality by specific tools based on the study designs We presented the results as a narrative synthesis regarding the frequency and duration of long COVID 19 signs and symptoms criteria used for diagnosis and potential risk factors We included 25 observational studies with moderate to high methodological quality considering 5440 participants The frequency of long COVID 19 ranged from 4 7 to 80 and the most prevalent signs symptoms were chest pain up to 89 fatigue up to 65 dyspnea up to 61 and cough and sputum production up to 59 Temporal criteria used to define long COVID 19 varied from 3 to 24 weeks after acute phase or hospital discharge Potentially associated risk factors were old age female sex severe clinical status a high number of comorbidities hospital admission and oxygen supplementation at the acute phase However limitations related to study designs added uncertainty to this finding None of the studies assessed the duration of signs symptoms The frequency of long COVID 19 reached up to 80 over the studies included and occurred between 3 and 24 weeks after acute phase or hospital discharge Chest pain fatigue dyspnea and cough were the most reported clinical manifestations attributed to the condition Based on these systematic review findings there is an urgent need to understand this emerging complex and challenging medical condition Proposals for diagnostic criteria and standard terminology are welcome 1 |
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393 Assessment of paediatric dental guidelines and caries management alternatives in the post COVID 19 period A critical review and clinical recommendations The first aim of this paper is to provide dental professionals caring for children and adolescents during and after the COVID 19 pandemic with a reference to international dental guidelines The second aim is to suggest minimally invasive treatment alternatives for caries management minimising the risk of viral cross infection and offering a safer clinical environment An evidence based pertinent literature search of different electronic databases was performed in addition to leading global dental authorities royal colleges and programmes All guidelines released in response to COVID 19 centred around minimising Aerosol Generating Procedures AGP impacting the provision of regular dental treatment of paediatric patients There was an emphasis on triaging and only treating emergency and urgent cases Special attention was given to medically compromised children in the guidelines Detailed guidelines for the dental environment and equipment were given This paper also summarised the relevant evidence based guidelines for the use of non invasive and minimally invasive caries management techniques Specific recommendations for dental management of paediatric patients during and in the post COVID 19 era are suggested Minimisation of AGP procedures and case based selection of biological non invasive or minimally invasive methods are recommended 0 |
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586 Clinical guidelines for caring for women with COVID 19 during pregnancy childbirth and the immediate postpartum period The spread of the novel coronavirus COVID 19 was declared a pandemic by the World Health Organization on 11th March 2020 Since then there has been a rapid rise in development of maternal and perinatal health guidelines related to COVID 19 The aim of this project was to develop a database of Australian and international recommendations relating to antenatal intrapartum and postpartum care of women during the COVID 19 pandemic in order to identify inconsistencies in clinical guidance We conducted weekly web searches from 30th March to 15th May 2020 to identify recommendations pertaining to the care of women during pregnancy labour and postpartum period from national or international professional societies specialist colleges Ministries of Health Australian state and territory governments and international guideline development organisations Individual recommendations were extracted and classified according to intervention type time period and patient population Findings were reported using descriptive analysis with areas of consensus and non consensus identified We identified 81 guidelines from 48 different organisations Generally there was high consensus across guidelines for specific interventions However variable guidance was identified on the use of nitrous oxide during labour administration of antenatal corticosteroids neonatal isolation after birth labour and birth companions and the use of disease modifying agents for treating COVID 19 Discrepancies between different guideline development organisations creates challenges for maternity care clinicians during the COVID 19 pandemic Collating recommendations and keeping up to date with the latest guidance can help clinicians provide the best possible care to pregnant women and their babies 0 |
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507 Health Benefits of Plant Based Nutrition Focus on Beans in Cardiometabolic Diseases Cardiovascular disease CVD is the leading cause of death worldwide claiming over 650 000 American lives annually Typically not a singular disease CVD often coexists with dyslipidemia hypertension type 2 diabetes T2D chronic system wide inflammation and obesity Obesity an independent risk factor for both CVD and T2D further worsens the problem with over 42 of adults and 18 5 of youth in the U S categorized as such Dietary behavior is a most important modifiable risk factor for controlling the onset and progression of obesity and related disease conditions Plant based eating patterns that include beans and legumes support health and disease mitigation through nutritional profile and bioactive compounds including phytochemical This review focuses on the characteristics of beans and ability to improve obesity related diseases and associated factors including excess body weight gut microbiome environment and low grade inflammation Additionally there are growing data that link obesity to compromised immune response and elevated risk for complications from immune related diseases Body weight management and nutritional status may improve immune function and possibly prevent disease severity Inclusion of beans as part of a plant based dietary strategy imparts cardiovascular metabolic and colon protective effects improves obesity low grade inflammation and may play a role in immune related disease risk management 0 |
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66 Characterising long COVID a living systematic review While it is now apparent clinical sequelae long COVID may persist after acute COVID 19 their nature frequency and aetiology are poorly characterised This study aims to regularly synthesise evidence on long COVID characteristics to help inform clinical management rehabilitation strategies and interventional studies to improve long term outcomes A living systematic review Medline CINAHL EBSCO Global Health Ovid WHO Global Research on COVID 19 database LitCovid and Google Scholar were searched till 17 March 2021 Studies including at least 100 people with confirmed or clinically suspected COVID 19 at 12 weeks or more post onset were included Risk of bias was assessed using the tool produced by Hoy i et al i Results were analysed using descriptive statistics and meta analyses to estimate prevalence A total of 39 studies were included 32 cohort 6 cross sectional and 1 case control Most showed high or moderate risk of bias None were set in low income countries and few included children Studies reported on 10 951 people 48 female in 12 countries Most included previously hospitalised people 78 8520 10 951 The longest mean follow up time was 221 7 SD 10 9 days post COVID 19 onset Over 60 physical and psychological signs and symptoms with wide prevalence were reported most commonly weakness 41 95 CI 25 to 59 general malaise 33 95 CI 15 to 57 fatigue 31 95 CI 24 to 39 concentration impairment 26 95 CI 21 to 32 and breathlessness 25 95 CI 18 to 34 37 95 CI 18 to 60 of patients reported reduced quality of life 26 10 39 of studies presented evidence of reduced pulmonary function Long COVID is a complex condition with prolonged heterogeneous symptoms The nature of studies precludes a precise case definition or risk evaluation There is an urgent need for prospective robust standardised controlled studies into aetiology risk factors and biomarkers to characterise long COVID in different at risk populations and settings CRD42020211131 1 |
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378 Gut Microbiota Dysbiosis Is a Crucial Player for the Poor Outcomes for COVID 19 in Elderly Diabetic and Hypertensive Patients A new infectious disease named COVID 19 caused by the coronavirus associated to severe acute respiratory syndrome SARS CoV 2 has become pandemic in 2020 The three most common pre existing comorbidities associated with COVID 19 related death are elderly diabetic and hypertensive people A common factor among these risk groups for the outcome of death in patients infected with SARS CoV 2 is dysbiosis with an increase in the proportion of bacteria with a pro inflammatory profile Due to this dysbiosis elderly diabetic and hypertensive people present a higher propensity to mount an inflammatory environment in the gut with poor immune editing culminating in a weakness of the intestinal permeability barrier and high bacterial product translocation to the bloodstream This scenario culminates in a low grade persistent and systemic inflammation In this context we propose here that high circulating levels of bacterial products like lipopolysaccharide LPS can potentiate the SARS CoV 2 induced cytokines including IL 6 being crucial for development of the cytokine storm in the severe form of the disease A better understanding on the possible correlation between gut dysbiosis and poor outcomes observed in elderly diabetic and hypertensive people can be useful for the development of new therapeutic strategies based on modulation of the gut microbiota 0 |
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104 Long COVID in a prospective cohort of home isolated patients Long term complications after coronavirus disease 2019 COVID 19 are common in hospitalized patients but the spectrum of symptoms in milder cases needs further investigation We conducted a long term follow up in a prospective cohort study of 312 patients 247 home isolated and 65 hospitalized comprising 82 of total cases in Bergen during the first pandemic wave in Norway At 6 months 61 189 312 of all patients had persistent symptoms which were independently associated with severity of initial illness increased convalescent antibody titers and pre existing chronic lung disease We found that 52 32 61 of home isolated young adults aged 16 30 years had symptoms at 6 months including loss of taste and or smell 28 17 61 fatigue 21 13 61 dyspnea 13 8 61 impaired concentration 13 8 61 and memory problems 11 7 61 Our findings that young home isolated adults with mild COVID 19 are at risk of long lasting dyspnea and cognitive symptoms highlight the importance of infection control measures such as vaccination 1 |
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35 Longitudinal immune dynamics of mild COVID 19 define signatures of recovery and persistence SARS CoV 2 has infected over 160 million and caused more than 3 million deaths to date Most individuals 80 have mild symptoms and recover in the outpatient setting but detailed studies of immune responses have focused primarily on moderate to severe COVID 19 We deeply profiled the longitudinal immune response in individuals with mild COVID beginning with early time points post infection 1 15 days and proceeding through convalescence to 100 days after symptom onset We correlated data from single cell analyses of peripheral blood cells serum proteomics virus specific cellular and humoral immune responses and clinical metadata Acute infection was characterized by vigorous coordinated innate and adaptive activation including an early cellular and proteomic signature that correlated with the amplitude of virus specific humoral responses after day 30 We characterized signals associated with recovery and convalescence to define a new signature of inflammatory cytokines gene expression and chromatin accessibility that persists in individuals with post acute sequelae of SARS CoV 2 infection PASC 1 |
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167 Health related quality of life issues including symptoms in patients with active COVID 19 or post COVID 19 a systematic literature review This systematic review was performed to identify all relevant health related quality of life HRQoL issues associated with COVID 19 A systematic literature search was undertaken in April 2020 In four teams of three reviewers each all abstracts were independently reviewed for inclusion by two reviewers Using a pre defined checklist of 93 criteria for each publication data extraction was performed independently by two reviewers and subsequently compared and discussed If necessary a third reviewer resolved any discrepancies The search was updated in February 2021 to retrieve new publications on HRQoL issues including issues related to the long term consequences of COVID 19 The search in April 2020 identified 3342 potentially relevant publications and 339 publications were selected for full text review and data extraction We identified 75 distinct symptoms and other HRQoL issues categorized into 12 thematic areas from general symptoms such as fever myalgia and fatigue to neurological and psychological issues The updated search revealed three extra issues experienced during active disease and long term problems with fatigue psychological issues and impaired cognitive function This first comprehensive systematic review provides a detailed overview of the wide range of HRQoL issues experienced by patients with COVID 19 throughout the course of the disease It demonstrates the devastating impact of the disease and provides critically important information for clinicians to enable them to better recognize the disease and to provide knowledge important for treatment and follow up The results provided the foundation for the international development of a COVID 19 specific patient reported HRQoL questionnaire 1 |
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426 Strategies to aid self isolation and quarantine for individuals with severe and persistent mental illness during the COVID 19 pandemic A systematic review Individuals with severe and persistent mental illness SPMI have a higher risk of contracting COVID 19 than individuals without SPMI In combination with physical distancing hygiene protocols and vaccines quarantine and self isolation are primary means of viral containment However individuals with SPMI may experience more difficulties with mandated quarantine or self isolation because of their illness es stigma and marginalization To date there is a lack of consensus on strategies that could aid such individuals in completing isolation This review aimed to synthesize evidence for interventions to support self isolation and mandated quarantine for COVID 19 among individuals with SPMIs We followed the PRISMA guidelines searching 19 electronic databases 9 published literature registries and 10 gray literature sources We looked for relevant randomized controlled trials quasi experimental studies and program evaluations of the effectiveness of relevant psychosocial pharmacological harm reduction and addiction management strategies to support isolation settings or quarantine requirements for individuals with any SPMI e g any mental disorder substance use disorder or their combination Of 10 298 total records that were located 5582 were duplicate citations Upon screening the remaining 4716 unique records by title and abstract we excluded a further 3562 records Only one original article met our inclusion criteria after reviewing the full texts of the remaining 1154 citations To support individuals experiencing homelessness during the COVID 19 pandemic San Francisco developed an isolation hotel that reduced COVID 19 hospital strain for 1009 participants 25 had a mental health disorder and 26 had a substance use disorder While 81 completed their hotel stay 48 patients had behavioral health needs that exceeded the hotels capabilities No other studies met our reviews eligibility criteria Most articles located by the search simply proposed solutions or discussed the challenges brought by COVID 19 for people with SPMIs While some documents went a step further e g shelter guidance documents to support individuals experiencing homelessness these rarely addressed individuals with SPMIs directly This systematic review evaluated evidence from published and gray literature on interventions to support self isolation and mandated COVID 19 quarantine for individuals with SPMIs Only one study met our inclusion criteria This study found a beneficial effect of a dedicated isolation hotel for individuals experiencing homelessness and COVID 19 where approximately 25 50 of the study sample had a mental or substance use disorder While there has been an abundance of COVID 19 protocols in general information for SPMIs is lacking As the pandemic continues and we better prepare for future pandemics developing protocols for supporting SPMIs in this context is imperative 0 |
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168 Post COVID 19 Syndrome Long COVID and Diabetes Challenges in Diagnosis and Management Post Covid 19 syndrome PCS is a major cause of morbidity In this article we intend to review the association and consequences of PCS and diabetes We reviewed all studies on Long Covid Post COVID 19 Syndrome and diabetes in PubMed and Google Scholar The symptoms of PCS can be due to organ dysfunction effects of hospitalisation and drugs or unrelated to these Type 2 diabetes mellitus has a bidirectional relationship with COVID 19 Presence of diabetes also influences PCS via various pathophysiological mechanisms COVID 19 can add to or exacerbate tachycardia sarcopenia and muscle fatigue and microvascular dysfunction and organ damage in patients with diabetes PCS in patients with diabetes could be detrimental in multiple ways Strict control of diabetes and other comorbidities supervised rehabilitation and physical exercise and optimal nutrition could help in reducing and managing PCS 1 |
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490 Laboratory confirmed vaccine induced immune thrombotic thrombocytopenia Retrospective analysis of reported cases after vaccination with ChAdOx 1 nCoV 19 in Germany Vaccine induced immune thrombotic thrombocytopenia VITT is a severe adverse event of SARS CoV 2 vaccination We describe the characteristics of patients reported in Germany based on the Brighton Collaboration BC case definition criteria for Thrombosis and Thrombocytopenia Syndrome TTS and focus on patients with complete anti platelet factor 4 PF4 antibody laboratory work up The adverse drug reaction database of the Paul Ehrlich Institute was queried for TTS cases following ChAdOx1 nCoV 19 vaccination from February 1 until May 21 2021 Cases with reports from the Greifswald laboratory were analysed in detail PF4 antibody tests were available for 69 suspected TTS cases reported to the Paul Ehrlich Institute of whom 52 patients fulfilled the BC case definition 37 71 women 15 29 men median age 46 0 years interquartile range 31 0 60 3 years Cerebral venous sinus thrombosis was confirmed in 37 71 additional multiple thromboses in 19 37 patients Twelve patients died Non survivors showed lower platelet counts compared to survivors median nadir 15 000 µL vs 49 000 µL p 0 0001 Combined anti PF4 heparin IgG ELISA and PF4 dependent platelet activation testing yielded sensitivity of 96 95 confidence interval 87 100 and specificity of 77 50 93 for TTS Four patients with thrombocytopenia but without thrombosis presented with severe headache or cerebral bleeding explaining the lower specificity VITT has high mortality and can present with isolated thrombocytopenia severe headache and bleeding Demonstration of platelet activating anti PF4 IgG has high sensitivity for TTS and captures a wider spectrum of clinically relevant VITT than the current BC case definition Deutsche Forschungsgemeinschaft 374031971 TRR240 Domagk Programm Universitätsmedizin Greifswald 0 |
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429 Post sequelae one year after hospital discharge among older COVID 19 patients a multi center prospective cohort study To systematically evaluate the prevalence of post sequelae and chronic obstructive pulmonary disease assessment test CAT scoring one year after hospital discharge among older COVID 19 patients as well as potential risk factors A multi center prospective cohort study involving 1 233 eligible older COVID 19 patients was conducted All patients were followed up between Mar 1 2021 and Mar 20 2021 CAT scoring was adopted to measure symptom burden in COVID 19 patients Of the 1233 eligible cases 630 51 1 reported at least one sequelae The top six post sequelae included fatigue 32 4 sweating 20 0 chest tightness 15 8 anxiety 11 4 myalgia 9 0 and cough 5 8 Severe patients had significantly higher percentage of fatigue sweating chest tightness myalgia and cough P 0 05 while anxiety was universal in all subjects Sweating anxiety palpitation edema of lower limbs smell reduction and taste change were emerging sequelae Disease severity during hospitalization OR 1 46 95 CI 1 15 1 84 P 0 002 and follow up time OR 0 71 95 CI 0 50 0 99 P 0 043 were independently associated with risk of post sequelae while disease severity during hospitalization was significantly associated with increased risk of emerging sequelae OR 1 33 95 CI 1 03 1 71 P 0 029 The median of CAT score was 2 0 5 in all patients and a total of 120 patients 9 7 had CAT scores 10 Disease severity during hospitalization OR 1 81 95 CI 1 23 2 67 P 0 003 and age OR 1 07 95 CI 1 04 1 09 P 0 001 were significantly associated with increased risk of CAT scores 10 While the dramatic decline in the prevalence rate of persistent symptoms is reassuring new sequelae among older COVID 19 patients cannot be ignored Disease severity during hospitalization age and follow up time contributed to the risk of post sequelae and CAT scoring one year after hospital discharge among older COVID 19 patients Our study provides valuable clues for long term post sequelae of the older COVID 19 patients as well as their risk factors 0 |
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85 Persistence of symptoms up to 10 months following acute COVID 19 illness COVID 19 symptoms are increasingly recognized to persist among a subset of individual following acute infection but features associated with this persistence are not well understood We aimed to identify individual features that predicted persistence of symptoms over at least 2 months at the time of survey completion Design Non probability internet survey Participants were asked to identify features of acute illness as well as persistence of symptoms at time of study completion We used logistic regression models to examine association between sociodemographic and clinical features and persistence of symptoms at or beyond 2 months Ten waves of a fifty state survey between June 13 2020 and January 13 2021 6 211 individuals who reported symptomatic COVID 19 illness confirmed by positive test or clinician diagnosis symptomatic COVID 19 illness Among 6 211 survey respondents reporting COVID 19 illness with a mean age of 37 8 SD 12 2 years and 45 1 female 73 9 white 10 0 Black 9 9 Hispanic and 3 1 Asian a total of 4946 79 6 had recovered within less than 2 months while 491 7 9 experienced symptoms for 2 months or more Of the full cohort 3 4 were symptomatic for 4 months or more and 2 2 for 6 months or more In univariate analyses individuals with persistent symptoms on average reported greater initial severity In logistic regression models older age was associated with greater risk of persistence OR 1 10 95 CI 1 01 1 19 for each decade beyond 40 otherwise no significant associations with persistence were identified for gender race ethnicity or income Presence of headache was significantly associated with greater likelihood of persistence OR 1 44 95 CI 1 11 1 86 while fever was associated with diminished likelihood of persistence OR 0 66 95 CI 0 53 0 83 A subset of individuals experience persistent symptoms from 2 to more than 10 months after acute COVID 19 illness particularly those who recall headache and absence of fever In light of this prevalence strategies for predicting and managing such sequelae are needed NA b Question b Which individuals are at greatest risk for post acute sequelae of COVID 19 b Findings b In this non probability internet survey among 6 211 individuals with symptomatic COVID 19 illness 7 9 experienced persistence of symptoms lasting 2 months or longer Older age but not other sociodemographic features was associated with risk for persistence as was headache b Meaning b Identifying individuals at greater risk for symptomatic persistence may facilitate development of targeted interventions 1 |
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37 Pulmonary rehabilitation in COVID 19 pneumonia sequelae so near yet so far b To evaluate the benefit of pulmonary rehabilitation a control group is a must to mitigate the effect of confounding factors like spontaneous resolution of lung damage learning effect and better mental status b https bit ly 3qy5sfe 1 |
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11 A longitudinal SARS CoV 2 biorepository for COVID 19 survivors with and without post acute sequelae SARS CoV 2 has swept across the globe causing millions of deaths worldwide Though most survive many experience symptoms of COVID 19 for months after acute infection Successful prevention and treatment of acute COVID 19 infection and its associated sequelae is dependent on in depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses Longitudinal biobanking provides a valuable resource of clinically integrated easily accessed and quality controlled samples for researchers to study differential multi organ system responses to SARS CoV 2 infection post acute sequelae of COVID 19 PASC and vaccination Adults with a history of a positive SARS CoV 2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS CoV 2 Biorepository NoCo COBIO Blood saliva stool nasopharyngeal specimens and extensive clinical and demographic data are collected at 4 time points over 6 months Patients are assessed for PASC during longitudinal follow up by physician led symptom questionnaires and physical exams This clinical trial registration is NCT04603677 We have enrolled and collected samples from 119 adults since July 2020 with 66 follow up rate Forty nine percent of participants assessed with a symptom surveillance questionnaire N 37 of 75 had PASC at any time during follow up up to 8 months post infection Ninety three percent of hospitalized participants developed PASC while 23 of those not requiring hospitalization developed PASC At 90 174 days post SARS CoV 2 diagnosis 67 of all participants had persistent symptoms N 37 of 55 and 85 percent of participants who required hospitalization during initial infection N 20 still had symptoms The most common symptoms reported after 15 days of infection were fatigue loss of smell loss of taste exercise intolerance and cognitive dysfunction Patients who were hospitalized for COVID 19 were significantly more likely to have PASC than those not requiring hospitalization however 23 of patients who were not hospitalized also developed PASC This patient matched multi matrix longitudinal biorepository from COVID 19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC Registered 27 October 2020 Retrospectively registered https clinicaltrials gov ct2 show NCT04603677 1 |
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178 Long COVID a cross sectional study of persisting symptoms biomarker and imaging abnormalities following hospitalisation for COVID 19 Large numbers of people are being discharged from hospital following COVID 19 without assessment of recovery In 384 patients mean age 59 9 years 62 male followed a median 54 days post discharge 53 reported persistent breathlessness 34 cough and 69 fatigue 14 6 had depression In those discharged with elevated biomarkers 30 1 and 9 5 had persistently elevated d dimer and C reactive protein respectively 38 of chest radiographs remained abnormal with 9 deteriorating Systematic follow up after hospitalisation with COVID 19 identifies the trajectory of physical and psychological symptom burden recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and or further investigation 1 |
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350 Opening Schools and Trends in SARS CoV 2 Transmission in European Countries b Objectives b Benefits of school attendance have been debated against SARS CoV 2 contagion risks This study examined the trends of contagion before and after schools reopened across 26 countries in the European Union b Methods b We compared the average values of estimated i R i sub i t i sub before and after school reopening identifying any significant increase with a one sample i t i test A meta analysis and meta regression analysis were performed to calculate the overall increase in i R i sub i t i sub for countries in the EU and to search for relationships between i R i sub i t i sub before schools reopened and the average increase in i R i sub i t i sub afterward b Results b The mean reproduction number increased in 16 out of 26 countries The maximum increase in i R i sub i t i sub was reached after a mean 28 days We found a negative relationship between the i R i sub i t i sub before school reopening and its increasing after that event By 45 days after the first day of school reopening the overall average increase in i R i sub i t i sub for the European Union was 23 b Conclusion b We observed a significant increase in the mean reproduction number in most European countries a public health issue that needs strategies to contain the spread of COVID 19 0 |
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658 Psychosocial interventions for improving engagement in care and health and behavioural outcomes for adolescents and young people living with HIV a systematic review and meta analysis Adolescents and young people comprise a growing proportion of new HIV infections globally yet current approaches do not effectively engage this group and adolescent HIV related outcomes are the poorest among all age groups Providing psychosocial interventions incorporating psychological social and or behavioural approaches offer a potential pathway to improve engagement in care and health and behavioural outcomes among adolescents and young people living with HIV AYPLHIV A systematic search of all peer reviewed papers published between January 2000 and July 2020 was conducted through four electronic databases Cochrane Library PsycINFO PubMed and Scopus We included randomized controlled trials evaluating psychosocial interventions aimed at improving engagement in care and health and behavioural outcomes of AYPLHIV aged 10 to 24 years Thirty relevant studies were identified Studies took place in the United States n 18 60 sub Saharan Africa Nigeria South Africa Uganda Zambia Zimbabwe and Southeast Asia Thailand Outcomes of interest included adherence to antiretroviral therapy ART ART knowledge viral load data sexual risk behaviours sexual risk knowledge retention in care and linkage to care Overall psychosocial interventions for AYPLHIV showed important small to moderate effects on adherence to ART SMD 0 3907 95 CI 0 1059 to 0 6754 21 studies n 2647 and viral load SMD 0 2607 95 CI 04518 to 0 0696 12 studies n 1566 The psychosocial interventions reviewed did not demonstrate significant impacts on retention in care n 8 sexual risk behaviours and knowledge n 13 viral suppression n 4 undetectable viral load n 5 or linkage to care n 1 among AYPLHIV No studies measured transition to adult services Effective interventions employed various approaches including digital and lay health worker delivery which hold promise for scaling interventions in the context of COVID 19 This review highlights the potential of psychosocial interventions in improving health outcomes in AYPLHIV However more research needs to be conducted on interventions that can effectively reduce sexual risk behaviours of AYPLHIV as well as those that can strengthen engagement in care Further investment is needed to ensure that these interventions are cost effective sustainable and resilient in the face of resource constraints and global challenges such as the COVID 19 pandemic 0 |
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444 Saliva Based ELISAs for Effective SARS CoV 2 Antibody Monitoring in Vaccinated Individuals In March 2020 the World Health Organization WHO declared a global health emergency the coronavirus disease 2019 COVID 19 pandemic Since then the development and implementation of vaccines against the virus amidst emerging cases of re infection has prompted researchers to work towards understanding how immunity develops and is sustained Serological testing has been instrumental in monitoring the development and persistence of antibodies against SARS CoV 2 infection however inconsistencies in detection have been reported by different methods As serological testing becomes more commonplace it is important to establish widespread and repeatable processes for monitoring vaccine efficacy Therefore we present enzyme linked immunosorbent assays ELISAs compatible for antibody detection in saliva as highly accurate efficacious and scalable tools for studying the immune response in individuals vaccinated against SARS CoV 2 0 |
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173 SARS CoV 2 as a superantigen in multisystem inflammatory syndrome in children Multisystem inflammatory syndrome in children MIS C is a rare but deadly new disease in children that rapidly progresses to hyperinflammation and shock and can lead to multiple organ failure if unrecognized It has been found to be temporally associated with the COVID 19 pandemic and is often associated with SARS CoV 2 exposure in children In this issue of the JCI Porritt Paschold et al identify restricted T cell receptor TCR β chain variable domain Vβ usage in patients with severe MIS C indicating a potential role for SARS CoV 2 as a superantigen These findings suggest that a blood test that determines the presence of specific TCRβ variable gene TRBV segments may identify patients at risk for severe MIS C 1 |
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464 HIV 1 genetic diversity and drug resistance mutations in the northern Brazilian region Brazil is a huge continental country with striking geographic differences which are well illustrated in the HIV AIDS epidemic Contrasting with the significant decline in the national AIDS detection rate in the last decade a linear growth has been reported in the Northern region Despite its public health and epidemiologic importance there is scarce HIV 1 molecular data from Northern Brazil This scoping review summarizes recent epidemiologic data with special emphasis on HIV 1 genetic diversity and antiretroviral drug resistance mutations in patients from the seven Northern states of Brazil Studies from the Northern Brazil on different HIV 1 genomic regions mostly pol protease reverse transcriptase sequences of naïve antiretroviral treated adults children were retrieved from PubMed MEDLINE electronic database These studies indicate a consistent molecular profile largely dominated by HIV 1 subtype B with minor contribution of subtypes F1 and C and infrequent detection of other subtypes A1 D K recombinants BF1 BC circulating recombinant forms CRF as the new CRF90_BF1 and CRF02_AG like CRF28 29_BF like CRF31_BC like and a potential new CRF_BF1 This pattern indicates a founder effect of subtype B and the introduction of non B subtypes and recombinants probably generated in the Southern Southeastern regions In naïve populations transmitted drug resistance TDR can impact the outcome of first line antiretroviral treatment and prophylactic preventive regimens In the Northern region TDR rates are moderate while patients failing highly active antiretroviral therapy HAART showed high prevalence of acquired drug resistance mutations The limited HIV 1 molecular data from Northern Brazil reflects the great challenges to generate comprehensive scientific data in isolated underprivileged areas It also highlights the need to invest in local capacity building which supported by adequate infrastructure and funding can promote robust research activities to help reduce the scientific asymmetries in the Northern region Currently the impacts of the overwhelming COVID 19 pandemic on the expanding HIV AIDS epidemic in Northern Brazil deserves to be closely monitored 0 |
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221 Case control study of neuropsychiatric symptoms following COVID 19 hospitalization in 2 academic health systems Neuropsychiatric symptoms may persist following acute COVID 19 illness but the extent to which these symptoms are specific to COVID 19 has not been established We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID 19 between March 2020 and May 2021 and compared them to individuals hospitalized for other indications during this period Natural language processing was applied to narrative clinical notes to identify neuropsychiatric symptom domains up to 150 days following hospitalization Among 6 619 individuals hospitalized for COVID 19 drawn from a total of 42 961 hospital discharges the most commonly documented symptom domains between 31 and 90 days after initial positive test were fatigue 13 4 mood and anxiety symptoms 11 2 and impaired cognition 8 0 In models adjusted for sociodemographic features and hospital course none of these were significantly more common among COVID 19 patients indeed mood and anxiety symptoms were less frequent adjusted OR 0 72 95 CI 0 64 0 92 Between 91 and 150 days after positivity most commonly detected symptoms were fatigue 10 9 mood and anxiety symptoms 8 2 and sleep disruption 6 8 with impaired cognition in 5 8 Frequency was again similar among non COVID 19 post hospital patients with mood and anxiety symptoms less common aOR 0 63 95 CI 0 52 0 75 Neuropsychiatric symptoms were common up to 150 days after initial hospitalization but occurred at generally similar rates among individuals hospitalized for other indications during the same period Post acute sequelae of COVID 19 thus may benefit from standard if less specific treatments developed for rehabilitation after hospitalization R01MH120227 R01MH116270 Perlis 1 |
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376 Secondary school students perception of the online teaching experience during COVID 19 The impact on mental wellbeing and specific learning difficulties Student engagement and concentration is critical for successful learning Due to the COVID 19 pandemic there has been a dramatic increase in the use of online learning which may affect engagement and concentration particularly for those students with specific learning difficulties Students would show lower scores on all the measures of student experience when judging these during online learning versus learning within the classroom This negative impact of online learning on concentration engagement perceived learning and self worth compared to classroom education would be more significant for those with specific learning difficulties The drop in student experience scores due to online learning would be associated with poorer mental well being Four hundred seven pupils aged 11 18 years at a secondary education school in Wales A retrospective online survey comparing pupils normal classroom experience to learning online during the first national lockdown in the United Kingdom March July 2020 Pupils learning experiences concentration engagement ability to learn and self worth from learning were significantly lower for online learning compared to the classroom learning These differences were more marked in students with specific learning difficulties Perceived ability to learn and engage during classroom and online learning were also associated with mental well being The move to online learning appears to have affected students ability to concentrate and engage in their schoolwork and appears to have reduced their ability to learn and get self worth from their work These decreases are associated with a decrease in mental well being The effects appear to be exacerbated in some students with specific learning difficulties 0 |
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675 Paediatric and adolescent asthma A narrative review of telemedicine and emerging technologies for the post COVID 19 era Children and young people with asthma need regular monitoring to maintain good asthma control prevent asthma attacks and manage comorbidities The COVID 19 pandemic has resulted in healthcare professionals making fundamental changes to the way healthcare is delivered and for patients and families adapting to these changes Comprehensive remotely delivered technology based healthcare closer to the patients home reducing hospital footfall and possibly reducing carbon footprint is likely to be one of the important collateral effects of the pandemic Telemedicine is anticipated to impact everyone involved in healthcare providers and patients alike It is going to bring changes to organization work areas and work culture in healthcare Healthcare providers policymakers and those accessing healthcare services will experience the impact of technology based healthcare delivery Telemedicine can play an exciting role in the management of childhood asthma by delivering high quality care closer to the childs home However unlike adults children still need to be accompanied by their carers for virtual care Policymakers will need to take into account potential additional costs as well as the legal ethical and cultural implications of large scale use of telemedicine In this narrative review we review evidence regarding the role of telemedicine and related emerging technologies in paediatric and adolescent asthma Although there are gaps in the current knowledge there is evidence demonstrating the important role of telemedicine in management of childhood and adolescent asthma However there is an urgent need for healthcare researchers and policymakers to focus on improving the technologies and address the disparities in accessing novel technology based management strategies to improve asthma care 0 |
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404 Systematic investigation of a potential epidemiological and genetic association between male androgenetic alopecia and COVID 19 Male androgenetic alopecia AGA has been implicated as a putative risk factor in severe COVID 19 based on high incidences of advanced AGA in male hospitalized COVID 19 patients Research further suggests that androgen signalling which plays a central role in AGA aetiology promotes SARS CoV 2 infection and is associated with severe COVID 19 symptoms in men We aimed to systematically investigate a potential association between AGA and COVID 19 both on an epidemiological and a genetic level in a large single population cohort We performed regression genetic correlation and polygenic risk score PRS analyses using data from the UK Biobank and published GWAS data on AGA and COVID 19 Our analyses did not reveal any significant epidemiological or genome wide genetic association between AGA and severe COVID 19 Pathway based PRS analyses however revealed a significant association in specific pathways namely vitamin metabolism natural killer cell mediated cytotoxicity WNT signalling and aryl hydrocarbon receptor signalling We restricted our analyses to the white British population and used self reported AGA status Sample size may be a limitation in our regression and PRS analyses Our data yield no evidence for an epidemiological association between AGA and COVID 19 but suggest that a shared genetic basis for both traits exists in specific pathways 0 |
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337 The neurological symptoms of COVID 19 a systematic overview of systematic reviews comparison with other neurological conditions and implications for healthcare services In response to the rapid spread of COVID 19 this paper provides health professionals with better accessibility to available evidence summarising findings from a systematic overview of systematic reviews of the neurological symptoms seen in patients with COVID 19 Implications of so called Long Covid on neurological services and primary care and similarities with other neurological disorders are discussed Firstly a systematic overview of current reviews of neurological symptoms of COVID 19 was conducted Secondly the implications of these findings are discussed in relation to the potential effect on neurological services and the similarities in the experience of patients with COVID 19 and those with other neurological disorders A total of 45 systematic reviews were identified within seven databases published between 11 April 2020 and 15 October 2020 following a search in June 2020 updated on 20 October 2020 The results indicated that COVID 19 exhibits two types of neurological symptoms life threatening symptoms such as Guillain Barre Syndrome GBS and encephalitis and less devastating symptoms such as fatigue and myalgia Many of these so called lesser symptoms appear to be emerging as longer term for some sufferers and have been recently labelled Long Covid When compared these less devastating symptoms are very similar to other neurological conditions such as chronic fatigue syndrome CFS and functional neurological disorder FND Implications for neurological healthcare services in the United Kingdom UK may include longer waiting times and a need for more resources including more qualified health professionals There is also a possible change effect on health professionals perceptions of other neurological conditions such as CFS and FND Future research is recommended to explore changes in health professionals perceptions of neurological symptoms because of COVID 19 1 |
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130 Chronic post COVID 19 syndrome and chronic fatigue syndrome Is there a role for extracorporeal apheresis As millions of patients have been infected by SARS CoV 2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease This overwhelming phenomenon has not been well defined and has been called post COVID syndrome or long COVID 1 There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis In both disorders neurotransmitter receptor antibodies against ß adrenergic and muscarinic receptors may play a key role We found similar elevation of these autoantibodies in both patient groups Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome Therefore such a form of neuropheresis may provide a promising therapeutic option for patients with post COVID 19 syndrome This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved 1 |
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673 Noninvasive respiratory support and patient self inflicted lung injury in COVID 19 a narrative review COVID 19 pneumonia is associated with hypoxaemic respiratory failure ranging from mild to severe Because of the worldwide shortage of ICU beds a relatively high number of patients with respiratory failure are receiving prolonged noninvasive respiratory support even when their clinical status would have required invasive mechanical ventilation There are few experimental and clinical data reporting that vigorous breathing effort during spontaneous ventilation can worsen lung injury and cause a phenomenon that has been termed patient self inflicted lung injury P SILI The aim of this narrative review is to provide an overview of P SILI pathophysiology and the role of noninvasive respiratory support in COVID 19 pneumonia Respiratory mechanics vascular compromise viscoelastic properties lung inhomogeneity work of breathing and oesophageal pressure swings are discussed The concept of P SILI has been widely investigated in recent years but controversies persist regarding its mechanisms To minimise the risk of P SILI intensivists should better understand its underlying pathophysiology to optimise the type of noninvasive respiratory support provided to patients with COVID 19 pneumonia and decide on the optimal timing of intubation for these patients 0 |
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52 The long term sequelae of COVID 19 an international consensus on research priorities for patients with pre existing and new onset airways disease Persistent ill health after acute COVID 19 referred to as long COVID the post acute COVID 19 syndrome or the post COVID 19 condition has emerged as a major concern We undertook an international consensus exercise to identify research priorities with the aim of understanding the long term effects of acute COVID 19 with a focus on people with pre existing airways disease and the occurrence of new onset airways disease and associated symptoms 202 international experts were invited to submit a minimum of three research ideas After a two phase internal review process a final list of 98 research topics was scored by 48 experts Patients with pre existing or post COVID 19 airways disease contributed to the exercise by weighting selected criteria The highest ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre existing airways disease High priority was also assigned to comparisons of the prevalence and severity of post COVID 19 fatigue sarcopenia anxiety depression and risk of future cardiovascular complications in patients with and without pre existing airways disease Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions This prioritisation process could also be adapted to other non respiratory aspects of long COVID 1 |
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329 A map of metabolic phenotypes in patients with myalgic encephalomyelitis chronic fatigue syndrome Myalgic encephalomyelitis chronic fatigue syndrome ME CFS is a debilitating disease usually presenting after infection Emerging evidence supports that energy metabolism is affected in ME CFS but a unifying metabolic phenotype has not been firmly established We performed global metabolomics lipidomics and hormone measurements and we used exploratory data analyses to compare serum from 83 patients with ME CFS and 35 healthy controls Some changes were common in the patient group and these were compatible with effects of elevated energy strain and altered utilization of fatty acids and amino acids as catabolic fuels In addition a set of heterogeneous effects reflected specific changes in 3 subsets of patients and 2 of these expressed characteristic contexts of deregulated energy metabolism The biological relevance of these metabolic phenotypes metabotypes was supported by clinical data and independent blood analyses In summary we report a map of common and context dependent metabolic changes in ME CFS and some of them presented possible associations with clinical patient profiles We suggest that elevated energy strain may result from exertion triggered tissue hypoxia and lead to systemic metabolic adaptation and compensation Through various mechanisms such metabolic dysfunction represents a likely mediator of key symptoms in ME CFS and possibly a target for supportive intervention 1 |
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12 Long covid mechanisms risk factors and management Since its emergence in Wuhan China covid 19 has spread and had a profound effect on the lives and health of people around the globe As of 4 July 2021 more than 183 million confirmed cases of covid 19 had been recorded worldwide and 3 97 million deaths Recent evidence has shown that a range of persistent symptoms can remain long after the acute SARS CoV 2 infection and this condition is now coined long covid by recognized research institutes Studies have shown that long covid can affect the whole spectrum of people with covid 19 from those with very mild acute disease to the most severe forms Like acute covid 19 long covid can involve multiple organs and can affect many systems including but not limited to the respiratory cardiovascular neurological gastrointestinal and musculoskeletal systems The symptoms of long covid include fatigue dyspnea cardiac abnormalities cognitive impairment sleep disturbances symptoms of post traumatic stress disorder muscle pain concentration problems and headache This review summarizes studies of the long term effects of covid 19 in hospitalized and non hospitalized patients and describes the persistent symptoms they endure Risk factors for acute covid 19 and long covid and possible therapeutic options are also discussed 1 |
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333 More Than 50 Long Term Effects of COVID 19 A Systematic Review and Meta Analysis b Background b COVID 19 caused by SARS CoV 2 can involve sequelae and other medical complications that last weeks to months after initial recovery which has come to be called Long COVID or COVID long haulers This systematic review and meta analysis aims to identify studies assessing long term effects of COVID 19 and estimates the prevalence of each symptom sign or laboratory parameter of patients at a post COVID 19 stage b Methods b LitCOVID PubMed and Medline and Embase were searched by two independent researchers All articles with original data for detecting long term COVID 19 published before 1 sup st sup of January 2021 and with a minimum of 100 patients were included For effects reported in two or more studies meta analyses using a random effects model were performed using the MetaXL software to estimate the pooled prevalence with 95 CI Heterogeneity was assessed using i I i sup 2 sup statistics This systematic review followed Preferred Reporting Items for Systematic Reviewers and Meta analysis PRISMA guidelines although the study protocol was not registered b Results b A total of 18 251 publications were identified of which 15 met the inclusion criteria The prevalence of 55 long term effects was estimated 21 meta analyses were performed and 47 910 patients were included The follow up time ranged from 14 to 110 days post viral infection The age of the study participants ranged between 17 and 87 years It was estimated that 80 95 CI 65 92 of the patients that were infected with SARS CoV 2 developed one or more long term symptoms The five most common symptoms were fatigue 58 headache 44 attention disorder 27 hair loss 25 and dyspnea 24 All meta analyses showed medium n 2 to high heterogeneity n 13 b Conclusions b In order to have a better understanding future studies need to stratify by sex age previous comorbidities the severity of COVID 19 ranging from asymptomatic to severe and duration of each symptom From the clinical perspective multi disciplinary teams are crucial to developing preventive measures rehabilitation techniques and clinical management strategies with whole patient perspectives designed to address long COVID 19 care 1 |
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521 Parenting in a Pandemic Parental Stress Anxiety and Depression Among Parents During the Government Initiated Physical Distancing Measures Following the First Wave of COVID 19 Drawing on the tenets of family stress theory the aim of this study is to examine parents perceived stress symptoms of anxiety depression and associated risk and protective factors across demographic subgroups during in the first wave of the COVID 19 pandemic Norwegian parents N 2 868 79 5 mothers with 1 child under 18 years of age completed an online survey two weeks after the implementation of government initiated distancing measures The survey includes measures of COVID related risk factors parental stress burnout depression anxiety anger of parents toward children difficulty working from home and positive beliefs about worry and protective factors self efficacy and social support Mothers parents living with more than one child and parents with a psychiatric diagnosis reported greater levels of parental stress more burnout and more anger toward their children as well as less social support Almost 25 of the parents reported anxiety and depression that are clinically significant Parents who followed distancing measures reported significantly higher distress Anger of parents toward children explains 41 of the variation in parental stress The findings indicate that parents have experienced symptoms of deteriorated mental health due to the COVID 19 pandemic including parental stress anxiety and depression The study presents practical implications for meso and macro level policymaking and offers support to further the potential aims of public health and clinical interventions Future studies to monitor long term aversive mental health outcomes among parents are warranted This article is protected by copyright All rights reserved 0 |
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412 Understanding neutralising antibodies against SARS CoV 2 and their implications in clinical practice SARS CoV 2 is a newly identified member of the coronavirus family that has caused the Coronavirus disease 2019 COVID 19 pandemic This rapidly evolving and unrelenting SARS CoV 2 has disrupted the lives and livelihoods of millions worldwide As of 23 August 2021 a total of 211 373 303 COVID 19 cases have been confirmed globally with a death toll of 4 424 341 A strong understanding of the infection pathway of SARS CoV 2 and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments In this review we discuss the current understanding of neutralising antibodies NAbs and their implications in clinical practice The aspects include the pathophysiology of the immune response particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance We summarise the onset and persistence of IgA IgM and IgG antibodies and we explore their roles in neutralising SARS CoV 2 their persistence in convalescent individuals and in reinfection Furthermore we also review the applications of neutralising antibodies in the clinical setting from predictors of disease severity to serological testing to vaccinations and finally in therapeutics such as convalescent plasma infusion 0 |
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569 COVID 19 Vaccines in Children with Cows Milk and Food Allergies The COVID 19 pandemic is the most challenging global health crisis of our times Vaccination against COVID 19 plays a key role to control the current pandemic situation The risk of allergic reactions to new COVID 19 vaccines is low However there is a debate on the safety in allergic patients following post marketing findings by different agencies Our aim is to understand from current experiences whether children with cows milk or food allergy are at higher risk than a general population for allergic reactions to COVID 19 vaccines Current data indicate that patients with a history of allergy to cows milk or other foods even if severe should receive COVID 19 vaccine in a setting with availability of treatments for anaphylactic reactions and under medical supervision Recipients should be discharged after a protracted observation period of 30 min if no reaction developed 0 |
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623 Immunogenicity of an inactivated SARS CoV 2 vaccine in people living with HIV 1 a non randomized cohort study Inactivated COVID 19 vaccines are safe and effective in the general population with intact immunity However their safety and immunogenicity have not been demonstrated in people living with HIV PLWH 42 HIV 1 infected individuals who were stable on combination antiretroviral therapy cART and 28 healthy individuals were enrolled in this open label two arm non randomized study at Hubei Provincial Center for Disease Control and Prevention China Two doses of an inactivated COVID 19 vaccine BBIBP CorV were given on April 22 2021 and May 25 2021 respectively The reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions Humoral responses were measured by anti spike IgG ELISA and surrogate neutralization assays Cell mediated immune responses and vaccine induced T cell activation were measured by flow cytometry All the HIV 1 infected participants had a CD4 sup sup T cell count 200 cells μL both at baseline 659 0 221 9 cells μL and 4 weeks after vaccination 476 9 150 8 cells μL No solicited adverse reaction was observed among all participants Similar binding antibody neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals PLWH with low baseline CD4 sup sup CD8 sup sup T cell ratios 0 6 generated lower antibody responses after vaccination than PLWH with medium 0 6 1 0 or high 1 0 baseline CD4 sup sup CD8 sup sup T cell ratios P 0 01 The CD3 sup sup CD4 sup sup and CD8 sup sup T cell counts of PLWH decreased significantly after vaccination P 0 0001 but it did not lead to any adverse clinical manifestation Moreover we found that the general HIV 1 viral load among the PLWH cohort decreased significantly after vaccination P 0 0192 The alteration of HIV 1 viral load was not significantly associated with the vaccine induced CD4 sup sup T cell activation P 0 2 Our data demonstrated that the inactivated SARS CoV 2 vaccine was safe immunogenic in PLWH who are stable on cART with suppressed viral load and CD4 sup sup T cell count 200 cells μL However the persistence of the vaccine induced immunities in PLWH need to be further investigated 0 |
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451 Mal adaptations A qualitative evidence synthesis of opioid agonist therapy during major disruptions Opioid agonist therapy OAT has been severely disrupted by the COVID 19 pandemic The risks of opioid withdrawal overdose and diversion have increased so there is an urgent need to adapt OAT to best support people who use drugs PWUD This review examines the views and experiences of PWUD health care providers and health system administrators on OAT during major disruptions to medical care to inform appropriate health system responses during the current pandemic and beyond We conducted a systematic review and qualitative evidence synthesis We searched three comprehensive datasets for qualitative and mixed methods studies that examined OAT in the context of major disruptions such as natural disasters and analyzed included studies using thematic analysis and the constant comparative method We used conceptual frameworks of health systems resilience and adaptive systems to interpret our findings We included 10 studies published between 2002 and 2020 that examined OAT in the context of hurricanes earthquakes and terrorist attacks We organized our results into three themes uncertainty inconsistency and vulnerability regulatory inflexibility and lack of coordination The highly regulated but poorly coordinated systems of OAT provision lacked flexibility to adapt to major disruptions thereby manufacturing vulnerability for both PWUD and health workers OAT programs must be resilient and adaptable to face major disruptions while maintaining quality care Our findings provide guidance to develop and implement innovative strategies that increase the adaptive potential of OAT programs while focusing on the needs of PWUD 0 |
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163 Immunoinformatics approach for designing a universal multiepitope vaccine against Chandipura Virus Chandipura vesiculovirus CHPV is a fast emerging virus that causes acute encephalitis with a high death rate Because of its extensive prevalence in African and Asian countries this infection has become a global hazard and there is an urgent need to create an effective and non allergenic vaccine or appropriate treatment to combat it A vaccine candidate is offered utilizing a computational technique in this study To build a potential vaccine candidate viral protein sequences were acquired from the National Center for Biotechnology Information database and evaluated with several bioinformatics techniques to identify B cell and T cell epitopes V1 was shown to be superior in terms of various physicochemical qualities as well as highly immunogenic and non allergic Molecular docking revealed that the CHPV vaccine construct had a greater binding affinity with human Toll like receptors TLR 3 and TLR 8 and that it was stable in molecular dynamics simulations MEC CHPV was in silico cloned in the pET28a expression vector using codon optimization The current research identifies potential antigenic epitopes that could be used as vaccine candidates to eradicate the CHPV This in silico development of a CHPV vaccine with multiple epitopes could open the path for future rapid laboratory tests 1 |
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375 Telehealth Audiology and Virtual Hearing Screenings A Case Report Clinic closures across the United States in response to the coronavirus disease 2019 COVID 19 pandemic meant that many audiology services were reduced to phone calls video visits and modified services e g curbside mail ins drop offs Audiologists and other providers needed a way to manage hearing and ear related complaints via telehealth A simple pure tone air conduction threshold test performed at home was used to determine which patients needed to come into the clinic for an in person appointment This case will review a 56 year old male who was being treated for an idiopathic sudden sensorineural hearing loss prior to clinic closure He had on file a comprehensive audiogram at first onset of symptoms and was treated with oral steroids Virtual hearing testing was then utilized for a variety of other patients from teenagers to adults to triage hearing and ear related complaints while clinics were closed for in person visits 0 |
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209 Post COVID 19 Syndrome Long Haul Syndrome Description of a Multidisciplinary Clinic at Mayo Clinic and Characteristics of the Initial Patient Cohort To describe characteristics of a series of patients reporting prolonged symptoms after an infection with coronavirus disease 2019 COVID 19 This study describes the multidisciplinary COVID 19 Activity Rehabilitation Program established at Mayo Clinic to evaluate and treat patients with post COVID syndrome and reports the clinical characteristics of the first 100 patients receiving evaluation and management during the timeframe of June 1 2020 and December 31 2020 The cohort consisted of 100 patients mean age 45 4 14 2 years 68 women mean body mass index 30 2 kg m sup 2 sup presenting a mean of 93 days after infection Common preexisting conditions were respiratory 23 and mental health including depression and or anxiety 34 Most 75 had not been hospitalized for COVID 19 Common presenting symptoms ware fatigue 80 respiratory complaints 59 and neurological complaints 59 followed by subjective cognitive impairment sleep disturbance and mental health symptoms More than one third of patients 34 reported difficulties in performing basic activities of daily living Only 1 in 3 patients had returned to unrestricted work duty at the time of the analysis For most patients laboratory and imaging tests showed no abnormalities or were nondiagnostic despite debilitating symptoms Most patients required physical therapy occupational therapy or brain rehabilitation Face to face and virtual care delivery modalities were feasible Most of the patients did not have COVID 19 related symptoms that were severe enough to require hospitalization were younger than 65 years and were more likely to be female and most had no preexisting comorbidities before severe acute respiratory syndrome coronavirus 2 infection Symptoms including mood disorders fatigue and perceived cognitive impairment resulted in severe negative impacts on resumption of functional and occupational activities in patients experiencing prolonged effects 1 |
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576 Work of a paediatric bioethics centre during the COVID 19 pandemic first phase Decisions with an ethical component have been controversial during the COVID 19 pandemic whether leaked intensive care unit ICU rationing documents transfer of people to care homes to protect the National Health Service or the duty to treat patients despite inadequate personal protective equipment To counter criticism of ethics per se and to help those planning ethics support we describe the practical work of a childrens hospital bioethics team in supporting children families and clinicians during this unprecedented period Three phases of activity i preparation we composed several documents to support guide hospital teams and together with colleagues provided them to regional inpatient community and hospice settings We adapted existing mechanisms to combat workforce moral injury ii activity March June 2020 was highest in our rapid response service where children families consider difficult treatment decisions with medical teams Education provided pandemic webcasts on decision making and broader child health concerns Staff support was essential especially for those deployed to overwhelmed local adult ICUs Research ascertained young peoples views on the pandemic iii reflection focussed on a research about future re deployment to adult services and minimisation of moral distress injury b remote video conferencing parents participants experience ability to consider complex ethical issues and c role of faith non faith in societys recovery and childrens views Our bioethics teams role during the pandemic included case reviews via video conferencing many involving innovative therapy for severely unwell children with COVID 19 Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS CoV 2 together with their parents processes to protect healthcare staff from moral harm and research educational activity focused on paediatric specific ethical arising during the pandemic 0 |
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609 Grow and Advance through Intentional Networking A pilot program to foster connections within the Womens Empowerment and Leadership Initiative in the Society for Pediatric Anesthesia The Womens Empowerment and Leadership Initiative in the Society for Pediatric Anesthesia was established to support womens efforts to achieve promotion leadership positions and equity in pediatric anesthesiology through coaching mentoring sponsorship and networking Career advancement relies on the establishment of mentoring relationships within institutions and at regional and national levels Prior to the SARS CoV 2 COVID 19 pandemic networking was primarily conducted at large national meetings When national meetings were canceled by the COVID 19 pandemic the Womens Empowerment and Leadership Initiative sought to reduce networking barriers by creating a pilot program called Grow and Advance through Intentional Networking GAIN Monthly 1 h virtual GAIN sessions were developed based on topics requested by the Womens Empowerment and Leadership Initiative members Faculty facilitated psychologically safe small group discussions to maximize engagement We present an overview of our pilot GAIN program which has been well received by the Womens Empowerment and Leadership Initiative members and met with continuous demand for more sessions Professional networking is critical for career advancement and for developing and maintaining a sense of community and well being Early and mid career physicians depend on these relationships to facilitate academic productivity and promotion Programs like the Womens Empowerment and Leadership Initiative GAIN are critical for advancing our specialty and supporting the well being of pediatric anesthesiologists GAIN addresses barriers to professional networking including during the COVID 19 pandemic 0 |
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335 Covid 19 Breakthrough Infections in Vaccinated Health Care Workers Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 SARS CoV 2 rare breakthrough infections have been reported including infections among health care workers Data are needed to characterize these infections and define correlates of breakthrough and infectivity At the largest medical center in Israel we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic including mild symptoms or had known infection exposure These evaluations included epidemiologic investigations repeat reverse transcriptase polymerase chain reaction RT PCR assays antigen detecting rapid diagnostic testing Ag RDT serologic assays and genomic sequencing Correlates of breakthrough infection were assessed in a case control analysis We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS CoV 2 detection peri infection period with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold Ct values with respect to infectivity Among 1497 fully vaccinated health care workers for whom RT PCR data were available 39 SARS CoV 2 breakthrough infections were documented Neutralizing antibody titers in case patients during the peri infection period were lower than those in matched uninfected controls case to control ratio 0 361 95 confidence interval 0 165 to 0 787 Higher peri infection neutralizing antibody titers were associated with lower infectivity higher Ct values Most breakthrough cases were mild or asymptomatic although 19 had persistent symptoms 6 weeks The B 1 1 7 alpha variant was found in 85 of samples tested A total of 74 of case patients had a high viral load Ct value 30 at some point during their infection however of these patients only 17 59 had a positive result on concurrent Ag RDT No secondary infections were documented Among fully vaccinated health care workers the occurrence of breakthrough infections with SARS CoV 2 was correlated with neutralizing antibody titers during the peri infection period Most breakthrough infections were mild or asymptomatic although persistent symptoms did occur 1 |
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650 The Epidemiology of Drug Abuse Many Americans use alcohol and recreational drugs Some will develop substance use disorders that affect a persons brain and behavior leading to continued use despite problems caused We review the epidemiology of addiction in the United States including changes in use patterns over time highlighting rates in adolescents and young adults as well as adults An overview of the health and societal impacts of substance use is provided alongside the importance of multimodal evidence based treatment comprising psychosocial interventions and medication management The article concludes by exploring the impact of the coronavirus disease 2019 pandemic on people who use drugs and their access to treatment 0 |
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551 Scoping Review on the Impact of Outbreaks on Sexual and Reproductive Health Services Proposed Frameworks for Pre Intra and Postoutbreak Situations Recent experiences from global outbreaks have highlighted the severe disruptions in sexual and reproductive health services that expose women and girls to preventable health risks Yet to date there is no review studying the possible impact of outbreaks on sexual and reproductive health SRH i Methodology i Studies reporting outbreaks impacting sexual and reproductive health and pregnancy outcomes were identified using MEDLINE Embase and ISI WoS Reported impacts were reviewed at systems community and legislative levels The initial run listed 4423 studies the 37 studies that met all inclusion criteria were mainly from Latin America and Africa Studies on outbreaks of diseases like Zika and Ebola have documented declines in facility based deliveries contraceptive use and antenatal and institutional care due to burdened healthcare system Service usage was also impacted by a lack of trust in the healthcare system and system shocks including workforce capacity and availability At the community level poverty and lack of awareness were critical contributors to poor access to SRH services Assessing the target populations knowledge attitude beliefs and behavior and using health literacy principles for communication were fundamental for designing service delivery Online resources for SRH services were an acceptable medium of information among young adults In outbreak situations SRH and pregnancy outcomes were improved by implementing laboratory surveillance free of cost contraceptive services improved screening through professional training and quality of care In addition mobile health clinics were reported to be effective in remote areas i Knowledge Contribution i In outbreaks the interventions are categorized into preoutbreak during and postoutbreak periods The proposed steps can help to improve and do course correction in emergencies Though conducted before the COVID 19 crisis the authors believe that lessons can be drawn from the paper to understand and mitigate the impact of the pandemic on sexual and reproductive health services 0 |
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484 Novel Coronavirus Disease 2019 COVID 19 and Cytokine Storms for More Effective Treatments from an Inflammatory Pathophysiology The Novel Coronavirus Disease 2019 COVID 19 has swept the world and caused a global pandemic SARS CoV 2 seems to have originated from bats as their reservoir hosts over time Similar to SARS CoV this new virus also exerts its action on the human angiotensin converting enzyme 2 This action causes infections in cells and establishes an infectious disease COVID 19 Against this viral invasion the human body starts to activate the innate immune system in producing and releasing proinflammatory cytokines such as IL 6 IL 1β IL 8 TNF α and other chemokines such as G CSF IP10 and MCPl which all develop and increase the inflammatory response In cases of COVID 19 excessive inflammatory responses occur and exaggerated proinflammatory cytokines and chemokines are detected in the serum resulting in cytokine release syndrome or cytokine storm This causes coagulation abnormalities excessive oxidation developments mitochondrial permeability transition vital organ damage immune system failure and eventually progresses to disseminated intravascular coagulation and multiple organ failure Additionally the excessive inflammatory responses also cause mitochondrial dysfunction due to progressive and persistent stress This damages cells and mitochondria leaving products containing mitochondrial DNA and cell debris involved in the excessive chronic inflammation as damage associated molecular patterns Thus the respiratory infection progressively leads to disseminated intravascular coagulation from acute respiratory distress syndrome including vascular endothelial cell damage and coagulation fibrinolysis system disorders This condition causes central nervous system disorders renal failure liver failure and finally multiple organ failure Regarding treatment for COVID 19 the following are progressive and multiple steps for mitigating the excessive inflammatory response and subsequent cytokine storm in patients First administering of favipiravir to suppress SARS CoV 2 and nafamostat to inhibit ACE2 function should be considered Second anti rheumatic drugs monoclonal antibodies which act on the leading cytokines IL 1β IL 6 and or cytokine receptors such as tocilizumab should be administered as well Finally melatonin may also have supportive effects for cytokine release syndrome resulting in mitochondrial function improvement This paper will further explore these subjects with reports mostly from China and Europe 0 |
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417 Understanding the emotional response to Covid 19 information in news and social media A mental health perspective The impact of the Covid 19 pandemic and ensuing social restrictions has been profound affecting the health livelihoods and wellbeing of populations worldwide Studies have shown widespread effects on mental health with an increase in stress loneliness and depression symptoms related to the pandemic Media plays a critical role in containing and managing crises by informing society and fostering positive behavior change Social restrictions have led to a large increase in reliance on online media channels and this can influence mental health and wellbeing Anxiety levels for instance may be exacerbated by exposure to Covid related content contagion of negative sentiment among social networks and fake news In some cases this may trigger abstinence leading to isolation and limited access to vital information To be able to communicate distressing news during crises while protecting the wellbeing of individuals is not trivial it requires a deeper understanding of peoples emotional response to online and social media content This paper selectively reviews research into consequences of social media usage and online news consumption for wellbeing and mental health focusing on and discussing their effects in the context of the pandemic Advances in Artificial Intelligence and Data Science for example Natural Language Processing Sentiment Analysis and Emotion Recognition are discussed as useful methods for investigating effects on population mental health as the pandemic situation evolves We present suggestions for future research and for using these advances to assess large data sets of users online content to potentially inform strategies that enhance the mental health of social media users going forward 0 |
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17 Post COVID 19 pulmonary complications a single center experience Although the rate and severity of complications after coronavirus 2019 disease COVID 19 resolution is currently unknown evidence regarding their presence is increasing in the literature This study presents a series of cases with post COVID 19 short term pulmonary complications This is a single center retrospective case series study The demographic and clinical data were collected from the centers electronic records All the included cases were confirmed COVID 19 patients who had pulmonary complications even after their recovery Nineteen COVID 19 patients were involved in this study Fourteen of them were male 73 7 and only 5 26 3 cases were female with a mean age of 52 05 years 26 77 All of the patients developed severe COVID 19 and were admitted to intensive care unit ICU The average infection duration was 13 5 days 10 21 The most common complaints after recovery from COVID 19 were shortness of breath fever and hemoptysis Computed tomography scan showed different pulmonary abnormalities between the cases Different surgical procedures were performed for the patients according to their conditions such as decortications lobectomy and bullectomy More than half of the patients n 10 recovered and were discharged from hospital without complications five patients were admitted to the ICU 3 cases developed mucormycosis and one case passed away Following the resolution of COVID 19 patients may experience severe pulmonary complications that may last for months and can affect quality of life ICU admission or even death 1 |
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504 Challenges of online teaching during Covid 19 An exploratory factor analysis Covid 19 has forced academic institutions around the world to shift toward the digital platform for teaching The study aimed to find a possible model to understand the challenges of online teaching from home Literature review and expert opinion identified the issues related to students institutions instructors technology and content and based on the experts opinion the motivation construct was added To obtain the data faculty members of different universities of North India were approached and requested to fill a self administered questionnaire This data was analyzed for its reliability and validity Finally the factor loading of all the items was analyzed to determine the scale appropriability 0 |
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366 Prevention of infections by influenza virus and respiratory syncytial virus after removal of the lockdown measures There have recently been reports of unusual outbreaks of respiratory infections in children due to influenza virus and respiratory syncytial virus RSV during the summer in the southern hemisphere This phenomenon is attributed to the termination of the drastic hygiene measures to contain the pandemic triggered by the coronavirus disease 2019 COVID 19 The affected children were much older than anticipated Coincident with the end of the present lockdown in summer a similar situation could develop in Germany Physicians and hospitals should be alerted to such a possibility Interseasonal vaccines are not available for influenza but passive immunization against RSV could help to protect infants for whom appropriate indications exist according to the guidelines 0 |
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596 Comparison of Stress and Suicide Related Behaviors Among Korean Youths Before and During the COVID 19 Pandemic The COVID 19 pandemic has had a substantial psychological effect on young people A quantitative assessment of the association between the pandemic and stress and suicidality in youths is needed To investigate the association of the COVID 19 pandemic with self reported stress and suicide related behaviors in youths This cross sectional study used data from the the Korea Youth Risk Behavior Web based Survey KYRBWS conducted in 2019 and 2020 with youths aged 12 to 18 years Statistical analysis was performed from January to February 2021 The odds ratios ORs with 95 CIs for subjective stress level sadness or despair suicidal thoughts suicide planning and suicide attempts among 2020 participants were compared with those of the 2019 participants using multiple logistic regression analysis with complex sampling using weighted values The 48 443 youths in the 2019 KYRBWS 24 917 male youths 51 3 mean SD age 15 0 1 7 years and the 44 216 youths in the 2020 KYRBWS 23 103 male youths 52 5 mean SD age 15 1 1 7 years were compared The degree of subjective stress was lower in the 2020 participants than in the 2019 participants severe stress adjusted OR aOR 0 90 95 CI 0 83 0 97 very severe stress aOR 0 65 95 CI 0 60 0 72 Sadness or despair was also lower in the 2020 participants than in the 2019 participants aOR 0 81 95 CI 0 78 0 84 There were fewer suicide related behaviors including suicidal thoughts suicide planning and suicide attempts among the 2020 participants than among the 2019 participants suicidal thoughts aOR 0 77 95 CI 0 73 0 80 suicide planning aOR 0 88 95 CI 0 81 0 96 suicide attempts aOR 0 64 95 CI 0 58 0 70 This cross sectional study found that severe stress sadness or despair and suicide related behaviors had inverse associations with the early COVID 19 pandemic in Korean youths These findings suggest that levels of high stress decreased among Korean youths in the early period of the pandemic compared with prepandemic levels 0 |
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525 Computational Modeling of Human nCoV Protein Protein Interaction Network Novel coronavirus SARS CoV2 replicates the host cells genome by interacting with the host proteins Due to this fact the identification of virus and host protein protein interactions could be beneficial in understanding the disease transmission behavior of the virus as well as in potential COVID 19 drug identification International Committee on Taxonomy of Viruses ICTV has declared that nCoV is highly genetically similar to the SARS CoV epidemic in 2003 89 similarity With this hypothesis the present work focuses on developing a computational model for the nCoV Human protein interaction network using the experimentally validated SARS CoV Human protein interactions Initially level 1 and level 2 human spreader proteins are identified in the SARS CoV Human interaction network using Susceptible Infected Susceptible SIS model These proteins are considered potential human targets for nCoV bait proteins A gene ontology based fuzzy affinity function has been used to construct the nCoV Human protein interaction network at a 99 98 specificity threshold This also identifies 37 level 1 human spreaders for COVID 19 in the human protein interaction network 2474 level 2 human spreaders are subsequently identified using the SIS model The derived host pathogen interaction network is finally validated using six potential FDA listed drugs for COVID 19 with significant overlap between the known drug target proteins and the identified spreader proteins 0 |
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633 Extended SEIR Model for Health Policies Assessment Against the COVID 19 Pandemic the Case of Argentina This work presents an extended and age band compartmentalised SEIR model that allows describing the spread evolution of SARS CoV 2 and evaluating the effect of different detection rates vaccination strategies or immunity periods The model splits up the population into fifteen age groups of 5 years each linked through a statistical interaction matrix that includes seventeen health states within each age group An age dependent transmission rate takes into account infectious between the groups as well the effect of interventions such as quarantines and mobility restrictions Further the proposal includes a nonlinear switched controller for model tuning purposes guarantying a simple and fast adjusting process To illustrate the model potentials the particular case of COVID 19 evolution in Argentina is analysed by simulation of three scenarios i different detection levels combined with mobility restrictions ii vaccination campaigns with re opening of activities and iii vaccination campaigns with possible reinfections The results exhibit how the model can aid the authorities in the decision making process 0 |
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269 Pediatric Inflammatory Multisystem Syndrome Associated With SARS CoV 2 A Case Series Quantitative Systematic Review Pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 PIMS TS is infrequent but children might present as a life threatening disease In a systematic quantitative review we analyzed 11 studies of PIMS TS including 468 children reported before July 1 2020 We found a myriad of clinical features but we were able to describe common characteristics previously healthy school aged children persistent fever and gastrointestinal symptoms lymphopenia and high inflammatory markers Clinical syndromes such as myocarditis and Kawasaki disease were present in only one third of cases each one Pediatric intensive care unit admission was frequent although length of stay was less than 1 week and mortality was low Most patients received immunoglobulin or steroids although the level of evidence for that treatment is low The PIMS ST was recently described and the detailed quantitative pooled data will increase clinicians awareness improve diagnosis and promptly start treatment This analysis also highlights the necessity of future collaborative studies given the heterogeneous nature of the PIMS TS 1 |
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123 Consensus on treatment of multisystemic inflammatory syndrome associated with COVID 19 The pandemic caused by the SARS CoV 2 virus declared by the WHO in March 11th 2020 affects a small number of pediatric patients who mostly present mild respiratory compromise and favorable evolution However began to be observed in previously healthy children an increase in cases defined as Multisystemic Inflammatory Syndrome MIS C or Kawasaki like post COVID 19 KLC that evolve to shock and require hospitalization in the Pediatric Intensive Care Unit MIS C and KL C are characterized by fever signs of inflammation gastrointestinal symptoms and cardiovascular dysfunction associated with sever forms of presentation with higher incidence of hypotension and or shock In the laboratory markers of inflammation hypercoagulability and myocardial damage are observed Firstline drug treatment consists of intravenous immunoglobulin plus oral acetylsalicylic acid A multidisciplinary approach is recommended for an accurate diagnosis and an early and effective treatment in order to reduce morbidity and mortality 1 |
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205 Post COVID 19 syndrome among symptomatic COVID 19 patients A prospective cohort study in a tertiary care center of Bangladesh Post coronavirus disease COVID 19 syndrome includes persistence of symptoms beyond viral clearance and fresh development of symptoms or exaggeration of chronic diseases within a month after initial clinical and virological cure of the disease with a viral etiology We aimed to determine the incidence association and risk factors associated with development of the post COVID 19 syndrome We conducted a prospective cohort study at Dhaka Medical College Hospital between June 01 2020 and August 10 2020 All the enrolled patients were followed up for a month after clinical improvement which was defined according the World Health Organization and Bangladesh guidelines as normal body temperature for successive 3 days significant improvement in respiratory symptoms respiratory rate 25 breath minute with no dyspnea and oxygen saturation 93 without assisted oxygen inhalation Among the 400 recruited patients 355 patients were analyzed In total 46 patients developed post COVID 19 symptoms with post viral fatigue being the most prevalent symptom in 70 cases The post COVID 19 syndrome was associated with female gender relative risk RR 1 2 95 confidence interval CI 1 02 1 48 p 0 03 those who required a prolonged time for clinical improvement p 0 001 and those showing COVID 19 positivity after 14 days RR 1 09 95 CI 1 00 1 19 p 0 001 of initial positivity Patients with severe COVID 19 at presentation developed post COVID 19 syndrome p 0 02 Patients with fever RR 1 5 95 CI 1 05 2 27 p 0 03 cough RR 1 36 95 CI 1 02 1 81 p 0 04 respiratory distress RR 1 3 95 CI 1 4 1 56 p 0 001 and lethargy RR 1 2 95 CI 1 06 1 35 p 0 003 as the presenting features were associated with the development of the more susceptible to develop post COVID 19 syndrome than the others Logistic regression analysis revealed female sex respiratory distress lethargy and long duration of the disease as risk factors Female sex respiratory distress lethargy and long disease duration are critical risk factors for the development of post COVID 19 syndrome 1 |
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397 Systemic corticosteroids for the treatment of COVID 19 Systemic corticosteroids are used to treat people with COVID 19 because they counter hyper inflammation Existing evidence syntheses suggest a slight benefit on mortality So far systemic corticosteroids are one of the few treatment options for COVID 19 Nonetheless size of effect certainty of the evidence optimal therapy regimen and selection of patients who are likely to benefit most are factors that remain to be evaluated To assess whether systemic corticosteroids are effective and safe in the treatment of people with COVID 19 and to keep up to date with the evolving evidence base using a living systematic review approach We searched the Cochrane COVID 19 Study Register which includes PubMed Embase CENTRAL ClinicalTrials gov WHO ICTRP and medRxiv Web of Science Science Citation Index Emerging Citation Index and the WHO COVID 19 Global literature on coronavirus disease to identify completed and ongoing studies to 16 April 2021 We included randomised controlled trials RCTs that evaluated systemic corticosteroids for people with COVID 19 irrespective of disease severity participant age gender or ethnicity We included any type or dose of systemic corticosteroids We included the following comparisons systemic corticosteroids plus standard care versus standard care plus minus placebo dose comparisons timing comparisons early versus late different types of corticosteroids and systemic corticosteroids versus other active substances We excluded studies that included populations with other coronavirus diseases severe acute respiratory syndrome or Middle East respiratory syndrome corticosteroids in combination with other active substances versus standard care topical or inhaled corticosteroids and corticosteroids for long COVID treatment We followed standard Cochrane methodology To assess the risk of bias in included studies we used the Cochrane Risk of bias 2 tool for RCTs We rated the certainty of evidence using the GRADE approach for the following outcomes all cause mortality ventilator free days new need for invasive mechanical ventilation quality of life serious adverse events adverse events and hospital acquired infections We included 11 RCTs in 8075 participants of whom 7041 87 originated from high income countries A total of 3072 participants were randomised to corticosteroid arms and the majority received dexamethasone n 2322 We also identified 42 ongoing studies and 16 studies reported as being completed or terminated in a study registry but without results yet Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID 19 Systemic corticosteroids plus standard care versus standard care plus minus placebo We included 10 RCTs 7989 participants one of which did not report any of our pre specified outcomes and thus our analysis included outcome data from nine studies All cause mortality at longest follow up available systemic corticosteroids plus standard care probably reduce all cause mortality slightly in people with COVID 19 compared to standard care alone median 28 days risk difference of 30 in 1000 participants fewer than the control group rate of 275 in 1000 participants risk ratio RR 0 89 95 confidence interval CI 0 80 to 1 00 9 RCTs 7930 participants moderate certainty evidence Ventilator free days corticosteroids may increase ventilator free days MD 2 6 days more than control group rate of 4 days 95 CI 0 67 to 4 53 1 RCT 299 participants low certainty evidence Ventilator free days have inherent limitations as a composite endpoint and should be interpreted with caution New need for invasive ventilation the evidence is of very low certainty Because of high risk of bias arising from deaths that occurred before ventilation we are uncertain about the size and direction of the effects Consequently we did not perform analysis beyond the presentation of descriptive statistics Quality of life neurological outcome no data were available Serious adverse events we included data on two RCTs 678 participants that evaluated systemic corticosteroids compared to standard care plus minus placebo for adverse events and hospital acquired infections we included data on five RCTs 660 participants Because of high risk of bias heterogeneous definitions and underreporting we are uncertain about the size and direction of the effects Consequently we did not perform analysis beyond the presentation of descriptive statistics very low certainty evidence Different types dosages or timing of systemic corticosteroids We identified one study that compared methylprednisolone with dexamethasone The evidence for mortality and new need for invasive mechanical ventilation is very low certainty due to the small number of participants n 86 No data were available for the other outcomes We did not identify comparisons of different dosages or timing Outpatients with asymptomatic or mild disease Currently there are no studies published in populations with asymptomatic infection or mild disease Moderate certainty evidence shows that systemic corticosteroids probably slightly reduce all cause mortality in people hospitalised because of symptomatic COVID 19 Low certainty evidence suggests that there may also be a reduction in ventilator free days Since we are unable to adjust for the impact of early death on subsequent endpoints the findings for ventilation outcomes and harms have limited applicability to inform treatment decisions Currently there is no evidence for asymptomatic or mild disease non hospitalised participants There is an urgent need for good quality evidence for specific subgroups of disease severity for which we propose level of respiratory support at randomisation This applies to the comparison or subgroups of different types and doses of corticosteroids too Outcomes apart from mortality should be measured and analysed appropriately taking into account confounding through death if applicable We identified 42 ongoing and 16 completed but not published RCTs in trials registries suggesting possible changes of effect estimates and certainty of the evidence in the future Most ongoing studies target people who need respiratory support at baseline With the living approach of this review we will continue to update our search and include eligible trials and published data 0 |
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443 Study Designs to Assess Real World Interventions to Prevent COVID 19 b Background b In the face of the novel virus SARS CoV 2 scientists and the public are eager for evidence about what measures are effective at slowing its spread and preventing morbidity and mortality Other than mathematical modeling studies thus far evaluating public health and behavioral interventions at scale have largely been observational and ecologic focusing on aggregate summaries Conclusions from these studies are susceptible to bias from threats to validity such as unmeasured confounding concurrent policy changes and trends over time We offer recommendations on how to strengthen frequently applied study designs which have been used to understand the impact of interventions to reduce the spread of COVID 19 and suggest implementation focused pragmatic designs that moving forward could be used to build a robust evidence base for public health practice b Methods b We conducted a literature search of studies that evaluated the effectiveness of non pharmaceutical interventions and policies to reduce spread morbidity and mortality of COVID 19 Our targeted review of the literature aimed to explore strengths and weaknesses of implemented studies provide recommendations for improvement and explore alternative real world study design methods to enhance evidence based decision making b Results b Study designs such as pre post interrupted time series and difference in differences have been used to evaluate policy effects at the state or country level of a range of interventions such as shelter in place face mask mandates and school closures Key challenges with these designs include the difficulty of disentangling the effects of contemporaneous changes in policy and correctly modeling infectious disease dynamics Pragmatic study designs such as the SMART Sequential Multiple Assignment Randomized Trial stepped wedge and preference designs could be used to evaluate community re openings such as schools and other policy changes b Conclusions b As the epidemic progresses we need to move from i post hoc i analyses of available data appropriate for the beginning of the pandemic to proactive evaluation to ensure the most rigorous approaches possible to evaluate the impact of COVID 19 prevention interventions Pragmatic study designs while requiring initial planning and community buy in could offer more robust evidence on what is effective and for whom to combat the global pandemic we face and future policy decisions 0 |
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120 Pathogenesis of taste impairment and salivary dysfunction in COVID 19 patients Coronavirus disease 2019 COVID 19 is a highly transmissible pandemic disease caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 The characteristics of the disease include a broad range of symptoms from mild to serious to death with mild pneumonia to acute respiratory distress syndrome and complications in extrapulmonary organs Taste impairment and salivary dysfunction are common early symptoms in COVID 19 patients The mouth is a significant entry route for SARS COV 2 similar to the nose and eyes The cells of the oral epithelium taste buds and minor and major salivary glands express cell entry factors for SARS COV 2 such as ACE2 TMPRSS2 and Furin We describe the occurrence of taste impairment and salivary dysfunction in COVID 19 patients and show immunohistochemical findings regarding the cell entry factors in the oral tissue We review and describe the pathogeneses of taste impairment and salivary dysfunction Treatment for the oral disease is also described Recently it was reported that some people experience persistent and prolonged taste impairment and salivary dysfunction described as post COVID 19 syndrome or long COVID 19 after the acute illness of the infection has healed To resolve these problems it is important to understand the pathogenesis of oral complications Recently important advances have been reported in the understanding of gustatory impairment and salivary dysfunction Although some progress has been made considerable effort is still required for in depth elucidation of the pathogenesis 1 |
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25 Unraveling the Mystery Surrounding Post Acute Sequelae of COVID 19 More than one year since its emergence corona virus disease 2019 COVID 19 is still looming large with a paucity of treatment options To add to this burden a sizeable subset of patients who have recovered from acute COVID 19 infection have reported lingering symptoms leading to significant disability and impairment of their daily life activities These patients are considered to suffer from what has been termed as chronic or long COVID 19 or a form of post acute sequelae of COVID 19 and patients experiencing this syndrome have been termed COVID 19 long haulers Despite recovery from infection the persistence of atypical chronic symptoms including extreme fatigue shortness of breath joint pains brain fogs anxiety and depression that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease As opposed to the direct effects of the virus itself the immune response to severe acute respiratory syndrome coronavirus 2 SARS CoV 2 is believed to be largely responsible for the appearance of these lasting symptoms possibly through facilitating an ongoing inflammatory process In this review we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects and describe the multi organ long term manifestations of COVID 19 1 |
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179 Long term side effects and lingering symptoms post COVID 19 recovery Since the Coronavirus disease 2019 COVID 19 pandemic caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 our understanding regarding the pathophysiology and clinical manifestations of this disease have been improving However we still have limited data on long term effects and lingering symptoms of post COVID 19 recovery Despite predilection of COVID 19 for lungs multiple extra pulmonary manifestations appear in multiple organs and biological systems and with continued infection and recovery worldwide It is necessary that clinicians provide patients with previous SARS CoV 2 infection with expectations of long term effects during or after recovery from COVID 19 Herein we review the long term impact of COVID 19 on different organ systems reported from different clinical studies Understanding risk factors and signs and symptoms of long term consequences after recovery from COVID 19 will allow for proper follow up and management of the disease post recovery 1 |
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13 Long term outcomes of patients following hospitalization for coronavirus disease 2019 a prospective observational study Few data are available regarding follow up of patients with coronavirus disease 2019 COVID 19 after their discharge We aim to describe the long term outcomes of survivors of hospitalization for COVID 19 followed up first at an outpatient facility and subsequently by telephone Observational prospective study conducted at a tertiary general hospital Clinical and radiological progression was assessed and data were recorded on a standardized reporting form Patients were divided into three groups according to Pao sub 2 sub Fio sub 2 sub at hospitalization Pao sub 2 sub Fio sub 2 sub 300 Pao sub 2 sub Fio sub 2 sub 300 200 and Pao sub 2 sub Fio sub 2 sub 200 A logistic multivariate regression model was performed to identify factors associated with persistence of symptoms For facility follow up 302 individuals were enrolled Median follow up was 45 days after discharge 78 228 294 of patients had COVID 19 related symptoms 53 asthenia 56 respiratory symptoms and 40 122 302 had residual pulmonary radiographic lesions Pao sub 2 sub Fio sub 2 sub 200 was an independent predictor of persistent dyspnoea OR 1 87 95 CI 1 38 2 52 p 0 0001 Pao sub 2 sub Fio sub 2 sub 300 was associated with resolution of chest radiographic lesions OR 0 56 95 CI 0 42 0 74 p 0 0001 Fifty per cent of patients required specific medical follow up after the first consultation and were transferred to another physician A total of 294 patients were contacted for telephone follow up after a median follow up time of 7 months Fifty per cent of patients 147 294 still presented symptoms and 49 145 294 had psychological disorders Asthenia was identified in 27 78 294 and dyspnoea in 10 28 294 of patients independently of Pao sub 2 sub Fio sub 2 sub Patients with COVID 19 require long term follow up because of the persistence of symptoms patients with low Pao sub 2 sub Fio sub 2 sub during the acute illness require special attention 1 |
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653 After the pandemic perspectives on the future trajectory of COVID 19 There is a realistic expectation that the global effort in vaccination will bring the pandemic caused by severe acute respiratory syndrome coronavirus 2 SARS CoV 2 under control Nonetheless uncertainties remain about the type of long term association that the virus will establish with the human population and in particular whether coronavirus disease 2019 COVID 19 will become an endemic disease Although the trajectory is difficult to predict the conditions concepts and variables that influence this transition can be anticipated Persistence of SARS CoV 2 as an endemic virus perhaps with seasonal epidemic peaks may be fuelled by pockets of susceptible individuals and waning immunity after infection or vaccination changes in the virus through antigenic drift that diminish protection and re entries from zoonotic reservoirs Here we review relevant observations from previous epidemics and discuss the potential evolution of SARS CoV 2 as it adapts during persistent transmission in the presence of a level of population immunity Lack of effective surveillance or adequate response could enable the emergence of new epidemic or pandemic patterns from an endemic infection of SARS CoV 2 There are key pieces of data that are urgently needed in order to make good decisions we outline these and propose a way forward 0 |
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608 Pediatric Airway Management in Times of COVID 19 a Review of the Evidence and Controversies This review summarizes and provides a comprehensive narrative synthesis of the current evidence on pediatric airway management during the COVID 19 pandemic The safe care of children undergoing airway management is a primary concern for pediatric anesthesiologists The COVID 19 pandemic has brought challenges related to airway management and the use of personal protective equipment aerosol barriers and the need for simulation and intubation teams The risk of COVID 19 transmission to the health care worker may be lower in children due to the smaller volume of aerosol dispersal The implementation of vaccinations may further reduce the risk to health care workers Evidence demonstrating the impact of COVID 19 on airway outcomes in children is necessary to inform their care This review shows that pediatric airway management can be a safe procedure for both the patient and provider in the right setting The use of appropriate personal protective equipment particularly focusing on protection from aerosolized particles is paramount to reduce infection risk However there are opportunities for future research 0 |
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512 Assessment of SARS CoV 2 testing in children during a low prevalence period VIGIL study 1 SARS CoV 2 induces a broad spectrum of clinical manifestations which overlap with other viral infections very common in children We aimed to describe the percentage of positive SARS CoV 2 RT PCR tests in symptomatic and asymptomatic ambulatory children and to determine the predictive factors for positivity From June 1 to July 31 2020 we conducted a cross sectional prospective multicenter study 13 hospital emergency units and 59 ambulatory pediatricians throughout France Children under 15 years of age with a prescription of nasopharyngeal SARS CoV 2 RT PCR test were enrolled Among the 1 553 RT PCR tests 22 were positive 1 4 95 CI 0 9 2 1 In both univariate and multivariate analyses the predictive factors for positivity were age below 2 years OR 4 5 1 6 12 7 and history of contact OR 12 3 4 6 32 8 In an epidemic stage with low SARS CoV 2 circulation sampling of children with nonspecific symptoms and without known contact could be questioned 0 |
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396 Interplay between interleukin 6 signaling and the vascular endothelium in cytokine storms Interleukin 6 IL 6 plays a crucial role in host defense against infection and tissue injuries and is a bioindicator of multiple distinct types of cytokine storms In this review we present the current understanding of the diverse roles of IL 6 its receptors and its signaling during acute severe systemic inflammation IL 6 directly affects vascular endothelial cells which produce several types of cytokines and chemokines and activate the coagulation cascade Endothelial cell dysregulation characterized by abnormal coagulation and vascular leakage is a common complication in cytokine storms Emerging evidence indicates that a humanized anti IL 6 receptor antibody tocilizumab can effectively block IL 6 signaling and has beneficial effects in rheumatoid arthritis juvenile systemic idiopathic arthritis and Castlemans disease Recent work has also demonstrated the beneficial effect of tocilizumab in chimeric antigen receptor T cell therapy induced cytokine storms as well as coronavirus disease 2019 COVID 19 Here we highlight the distinct contributions of IL 6 signaling to the pathogenesis of several types of cytokine storms and discuss potential therapeutic strategies for the management of cytokine storms including those associated with sepsis and COVID 19 0 |
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6 Treatment Options for COVID 19 Related Guillain Barré Syndrome A Systematic Review of Literature Central nervous system complications are reported in an increasing number of patients with Coronavirus Disease 2019 COVID 19 COVID 19 related Guillain Barré syndrome GBS is of particular importance given its association with higher mortality rates and prolonged respiratory failure We conducted a systematic review of published cases for COVID 19 related GBS and provide a summary of clinical management strategies for these cases Sixty three studies including 86 patients were included Seventy six cases with reported outcome data were eligible for the outcome analysis Ninety nine percent of patients were diagnosed with COVID 19 before diagnosis of GBS median 14 d prior interquartile range 7 to 20 Intravenous immunotherapy intravenous immunoglobulin 0 4 g kg d for 5 d was the most frequently used treatment approach The review indicated that the outcome was not favorable in 26 of cases persistent neurological deficits A mortality rate of 3 5 was observed in patients with COVID 19 related GBS Although evidence to support specific treatments is lacking clinicians should consider the benefits of immunotherapy and plasma exchange in addition to the standard antimicrobial and supportive therapies for patients who meet the diagnostic criteria for acute sensory and motor polyradiculoneuritis Intravenous immunoglobulin treatment alone is not shown to result in improved outcomes or mortality More extensive studies aimed at exploring the neurological manifestations and complications of COVID 19 and distinctive treatment options for COVID 19 related GBS are warranted 1 |
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547 Prevalence of Smell or Taste Dysfunction Among Children With COVID 19 Infection A Systematic Review and Meta Analysis b Background b Smell and taste dysfunctions are common and have been reported as an early indicator of COVID 19 The prevalence of smell and taste dysfunctions among children with COVID 19 varies greatly across studies which remains to be summarized quantitatively This review aimed at examining the pooled prevalence of smell or taste dysfunctions among children with COVID 19 summarizing possible causes of the inconsistencies in the current estimates b Methods b Systematic searches of databases were conducted for literature published until 12 January 2021 Statistical analyses were performed using R software the pooled prevalence was combined using random effects model The Loney criteria were used for quality assessment b Results b A total of 18 eligible studies were included The results showed that the pooled prevalence of smell dysfunction among children with COVID 19 was 15 97 95 CI 8 18 23 77 the pooled prevalence of taste dysfunction among children with COVID 19 was 9 20 95 CI 4 25 14 16 the pooled prevalence of smell or taste dysfunction among children with COVID 19 was 15 50 95 CI 10 30 20 70 and the pooled prevalence of smell and taste dysfunction among children with COVID 19 was 20 21 95 CI 14 14 26 28 Higher smell or taste dysfunction rates were associated with being female younger age smaller sample size patients in Asia and with comorbidities b Conclusions b Evidence suggests that smell or taste dysfunctions were common among children with COVID 19 Further research is needed to identify effective strategies for preventing and treating smell and taste dysfunctions among children with COVID 19 0 |
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190 COVID lateral damage cardiovascular manifestations of SARS CoV 2 infection Early in the pandemic concern that cardiovascular effects would accompany COVID 19 was fueled by lessons from the first SARS epidemic knowledge that the SARS COV2 entry receptor Angiotensin converting enzyme 2 ACE2 is highly expressed in the heart early reports of myocarditis and first hand accounts by physicians caring for those with severe COVID 19 Over 18 months our understanding of the cardiovascular manifestations has expanded greatly leaving more new questions than those conclusively answered Cardiac involvement is common 20 but not uniformly observed in those who require treatment in a hospitalized setting Cardiac MRI studies raise the possibility of manifestations in those with minimal symptoms Some appear to experience protracted cardiovascular symptoms as part of a larger syndrome of post acute sequelae of COVID 19 Instances of vaccine induced thrombosis and myocarditis are exceedingly rare but illustrate the need to monitor the cardiovascular safety of interventions that induce inflammation Here we will summarize the current understanding of potential cardiovascular manifestations of SARS COV2 To provide proper context paradigms of cardiovascular injury due to other inflammatory processes will also be discussed Ongoing research and a deeper understanding COVID 19 may ultimately reveal new insight into the mechanistic underpinnings of cardiovascular disease Thus in this time of unprecedented suffering and risk to global health there exists the opportunity that well conducted translational research of SARS COV2 may provide health dividends that outlast the current pandemic 1 |
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106 Long COVID in Children Observations From A Designated Pediatric Clinic Systematic data are lacking on pediatric long COVID This study prospectively assessed 90 children with persistent symptoms who presented to a designated multidisciplinary clinic for long COVID In nearly 60 symptoms were associated with functional impairment at 1 7 months after the onset of infection A comprehensive structured evaluation revealed mild abnormal findings in approximately half the patients mainly in the respiratory aspect 1 |
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605 Lung Fibrosis after COVID 19 Treatment Prospects At the end of 2019 a highly contagious infection began its ominous conquest of the world It was soon discovered that the disease was caused by a novel coronavirus designated as SARS CoV 2 and the disease was thus abbreviated to COVID 19 COVID The global medical community has directed its efforts not only to find effective therapies against the deadly pathogen but also to combat the concomitant complications Two of the most common respiratory manifestations of COVID are a significant reduction in the diffusing capacity of the lungs DLCO and the associated pulmonary interstitial damage One year after moderate COVID the incidence rate of impaired DLCO and persistent lung damage still exceeds 30 and one third of the patients have severe DLCO impairment and fibrotic lung damage The persistent respiratory complications may cause substantial population morbidity long term disability and even death due to the lung fibrosis progression The incidence of COVID induced pulmonary fibrosis caused by COVID can be estimated based on a 15 year observational study of lung pathology after SARS Most SARS patients with fibrotic lung damage recovered within the first year and then remained healthy however in 20 of the cases significant fibrosis progression was found in 5 10 years Based on these data the incidence rate of post COVID lung fibrosis can be estimated at 2 6 after moderate illness What is worse there are reasons to believe that fibrosis may become one of the major long term complications of COVID even in asymptomatic individuals Currently despite the best efforts of the global medical community there are no treatments for COVID induced pulmonary fibrosis In this review we analyze the latest data from ongoing clinical trials aimed at treating post COVID lung fibrosis and analyze the rationale for the current drug candidates We discuss the use of antifibrotic therapy for idiopathic pulmonary fibrosis the IN01 vaccine glucocorticosteroids as well as the stromal vascular fraction for the treatment and rehabilitation of patients with COVID associated pulmonary damage 0 |
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162 Serum Metabolic Profile in Patients With Long Covid PASC Syndrome Clinical Implications b Background b Many patients who have been suffering by Covid 19 suffer of long Covid syndrome with symptoms of fatigue and muscular weakness that characterize post acute sequelae SARS CoV 2 infection PASC However there is limited knowledge about the molecular pathophysiology and about the serum profile of these patients b Methods b We studied the blood serum profile of 75 selected patients with previous confirmed Covid 19 2 months after hospital discharge who reported new onset fatigue muscle weakness and or dyspnea not present prior to the virus infection and independently from concomitant diseases and or clinical conditions b Results b All patients had very high serum concentrations of ferritin and D Dimer 87 and 72 of patients had clinically significant low levels of hemoglobin and albumin respectively Seventy three percentage had elevations in erythrocyte sedimentation rate and CRP Twenty seven percentage had elevations in LDH b Conclusions b The co existence of patient symptoms along with blood markers of coagulation protein disarrangement and inflammation suggests ongoing alterations in the metabolism promoting an inflammatory hypercatabolic state which maintains a vicious circles implicated in the persistence of PASC The persistence of altered D Dimer levels raises the possibility of long term risks of thromboembolic disease All these markers levels should be accurately evaluated in the long term follow up with individualized consideration for prophylactic nutritional anti inflammatory and or anticoagulant therapy if indicated 1 |
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389 The Community of Bilingual English Spanish Speakers Exploring Issues in Science and Health Experiences During the COVID 19 Pandemic Language diversity is increasing in the United States This growth has implications for language preference cost quality and client outcomes in health services settings However language diversity among medical and allied health professionals is lacking Education pipeline programs are a mechanism to prepare bi and multi lingual diverse students to enter health careers The Community of Bilingual English Spanish Speakers Exploring Issues in Science and Health CBESS is one such program Through peer mentorship from Leadership Trainees LT and a multicomponent 17 month education curriculum CBESS was designed to increase interest in STEM careers among English Spanish bilingual high school youth In 2020 the COVID 19 pandemic interrupted high school students education and forced programs to innovate CBESS was no exception The most significant modifications were to a expectations of SRs for a successful Summer Virtual Research Program SVRP b LT roles and c scope and delivery of summer science content A preliminary evaluation was conducted from data collected through pre post surveys process data and focus groups Among the outcomes were a significant increase in science knowledge among SVRP youth participants as well as no significant differences between cohort 1 and 2 suggesting that changes did not impede program goals LTs highlighted skills needed and role of mentors Adaptations were successful and will continue with the 2021 cohort 0 |
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14 CSF rhinorrhoea post COVID 19 swab A case report and review of literature We report the case of a 59 year old male who presented with 2 months of persistent rhinorrhoea from left nostril post a nasal swab done for coryzal symptoms at the peak of the COVID 19 pandemic Beta 2 transferrin confirmed it to be a CSF leak and imaging showed a left middle cranial fossa encephalocele herniating into the sphenoid sinus as the site of the leak post swab The leak was treated endoscopically We describe the case history and management of this exceedingly rare complication of nasal swab for respiratory testing 1 |
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67 Persistent clotting protein pathology in Long COVID Post Acute Sequelae of COVID 19 PASC is accompanied by increased levels of antiplasmin Severe acute respiratory syndrome coronavirus 2 SARS Cov 2 induced infection the cause of coronavirus disease 2019 COVID 19 is characterized by acute clinical pathologies including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation Recently a new COVID 19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID 19 symptoms This new syndrome is commonly termed Long COVID Post Acute Sequelae of COVID 19 PASC Here we refer to it as Long COVID PASC Lingering symptoms persist for as much as 6 months or longer after acute infection where COVID 19 survivors complain of recurring fatigue or muscle weakness being out of breath sleep difficulties and anxiety or depression Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange we here investigate if the lingering symptoms that individuals with Long COVID PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals individuals with Type 2 Diabetes Mellitus T2DM with acute COVID 19 and those with Long COVID PASC symptoms We show that plasma samples from Long COVID PASC still contain large anomalous amyloid deposits microclots We also show that these microclots in both acute COVID 19 and Long COVID PASC plasma samples are resistant to fibrinolysis compared to plasma from controls and T2DM even after trypsinisation After a second trypsinization the persistent pellet deposits microclots were solubilized We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID 19 and Long COVID PASC versus the equivalent volume of fully digested fluid of the control samples and T2DM Of particular interest was a substantial increase in α 2 antiplasmin α2AP various fibrinogen chains as well as Serum Amyloid A SAA that were trapped in the solubilized fibrinolytic resistant pellet deposits Clotting pathologies in both acute COVID 19 infection and in Long COVID PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function 1 |
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72 Cardiac sequelae after coronavirus disease 2019 recovery a systematic review Coronavirus disease 2019 COVID 19 has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease To assess the range of cardiac sequelae after COVID 19 recovery PubMed Embase Scopus inception through 17 February 2021 and Google scholar 2019 through 17 February 2021 Prospective and retrospective studies case reports and case series Adult patients assessed for cardiac manifestations after COVID 19 recovery Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR Systematic review Thirty five studies fifteen prospective cohort seven case reports five cross sectional four case series three retrospective cohort and one ambidirectional cohort evaluating cardiac sequelae in 52 609 patients were included Twenty nine studies used objective cardiac assessments mostly cardiac magnetic resonance imaging CMR in 16 studies echocardiography in 15 electrocardiography ECG in 16 and cardiac biomarkers in 18 Most studies had a fair risk of bias The median time from diagnosis recovery to cardiac assessment was 48 days 1 180 days Common short term cardiac abnormalities 3 months included increased T1 proportion 30 T2 16 pericardial effusion 15 and late gadolinium enhancement 11 on CMR with symptoms such as chest pain 25 and dyspnoea 36 In the medium term 3 6 months common changes included reduced left ventricular global longitudinal strain 30 and late gadolinium enhancement 10 on CMR diastolic dysfunction 40 on echocardiography and elevated N terminal proB type natriuretic peptide 18 In addition COVID 19 survivors had higher risk risk ratio 3 95 CI 2 7 3 2 of developing heart failure arrythmias and myocardial infarction COVID 19 appears to be associated with persistent de novo cardiac injury after recovery particularly subclinical myocardial injury in the earlier phase and diastolic dysfunction later Larger well designed and controlled studies with baseline assessments are needed to better measure the extent of cardiac injury and its clinical impact 1 |
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527 Teleophthalmology and Artificial Intelligence As Game Changers in Ophthalmic Care After the COVID 19 Pandemic The current COVID 19 pandemic has boosted a sudden demand for telemedicine due to quarantine and travel restrictions The exponential increase in the use of telemedicine is expected to affect ophthalmology drastically The aim of this review is to discuss the utility effectiveness and challenges of teleophthalmological new tools for eyecare delivery as well as its implementation and possible facilitation with artificial intelligence We used the terms teleophthalmology telemedicine and COVID 19 retinal diseases and telemedicine virtual ophthalmology cost effectiveness of teleophthalmology pediatric teleophthalmology Artificial intelligence and ophthalmology Glaucoma and teleophthalmology and teleophthalmology limitations in the database of PubMed and selected the articles being published in the course of 2015 2020 After the initial search 321 articles returned as relevant A meticulous screening followed and eventually 103 published manuscripts were included and used as our references Emerging in the market teleophthalmology is showing great potential for the future of ophthalmological care benefiting both patients and ophthalmologists in times of pandemics The spectrum of eye diseases that could benefit from teleophthalmology is wide including mostly retinal diseases such as diabetic retinopathy retinopathy of prematurity age related macular degeneration but also glaucoma and anterior segment conditions Simultaneously artificial intelligence provides ways of implementing teleophthalmology easier and with better outcomes contributing as significant changing factors for ophthalmology practice after the COVID 19 pandemic 0 |
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259 The Impact of Post COVID 19 Syndrome on Self Reported Physical Activity i Background i A subgroup of patients recovering from COVID 19 experience persistent symptoms decreased quality of life increased dependency on others for personal care and impaired performance of activities of daily living However the long term effects of COVID 19 on physical activity PA in this subgroup of patients with persistent symptoms remain unclear i Methods i Demographics self reported average time spent walking per week as well as participation in activities pre COVID 19 and after three and six months of follow up were assessed in members of online long COVID 19 peer support groups i Results i Two hundred thirty nine patients with a confirmed COVID 19 diagnosis were included 83 women median IQR age 50 39 56 years Patients reported a significantly decreased weekly walking time after three months of follow up three months 60 15 120 min vs pre COVID 19 120 60 240 min week i p i 0 05 Six months after the onset of symptoms walking time was still significantly lower compared to pre COVID 19 but significantly increased compared to three months of follow up three months 60 15 120 min vs six months 90 30 150 min i p i 0 05 i Conclusions i Patients who experience persistent symptoms after COVID 19 may still demonstrate a significantly decreased walking time six months after the onset of symptoms More research is needed to investigate long term consequences and possible treatment options to guide patients during the recovery fromCOVID 19 1 |
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681 Asymptomatic SARS CoV 2 infection A systematic review and meta analysis Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID 19 pandemic Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity We searched PubMed Embase Web of Science and World Health Organization Global Research Database on COVID 19 between January 1 2020 and April 2 2021 to identify studies that reported silent infections at the time of testing whether presymptomatic or asymptomatic Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity By analyzing over 350 studies we estimate that the percentage of infections that never developed clinical symptoms and thus were truly asymptomatic was 35 1 95 CI 30 7 to 39 9 At the time of testing 42 8 95 prediction interval 5 2 to 91 1 of cases exhibited no symptoms a group comprising both asymptomatic and presymptomatic infections Asymptomaticity was significantly lower among the elderly at 19 7 95 CI 12 7 to 29 4 compared with children at 46 7 95 CI 32 0 to 62 0 We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions Without proactive policies to detect asymptomatic infections such as rapid contact tracing prolonged efforts for pandemic control may be needed even in the presence of vaccination 0 |
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456 Pregnancy and viral infections Mechanisms of fetal damage diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS CoV 2 and Zika virus Some maternal infections contracted before or during pregnancy can be transmitted to the fetus during gestation congenital infection during labor and childbirth perinatal infection and through breastfeeding postnatal infection The agents responsible for these infections can be viruses bacteria protozoa fungi Among the viruses most frequently responsible for congenital infections are Cytomegalovirus CMV Herpes simplex 1 2 Herpes virus 6 Varicella zoster Moreover Hepatitis B and C virus HIV Parvovirus B19 and non polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth Recently new viruses have emerged SARS Cov 2 and Zika virus of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy Viral infections in pregnancy can damage the fetus spontaneous abortion fetal death intrauterine growth retardation or the newborn congenital anomalies organ diseases with sequelae of different severity Some risk factors specifically influence the incidence of transmission to the fetus the timing of the infection in pregnancy the order of the infection primary or reinfection or chronic the duration of membrane rupture type of delivery socio economic conditions and breastfeeding Frequently infected neonates symptomatic at birth have worse outcomes than asymptomatic Many asymptomatic babies develop long term neurosensory outcomes The way in which the virus interacts with the maternal immune system the maternal fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal neonatal outcomes of maternal infections The maternal immune system undergoes functional adaptation during pregnancy once thought as physiological immunosuppression This adaptation crucial for generating a balance between maternal immunity and fetus is necessary to promote and support the pregnancy itself and the growth of the fetus When this adaptation is upset by the viral infection the balance is broken and the infection can spread and lead to the adverse outcomes previously described In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn 0 |
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361 The Trilogy of SARS CoV 2 in Pediatrics Part 3 Thrombosis Anticoagulant and Antiplatelet Considerations The hypercoagulable state induced by the severe acute respiratory syndrome coronavirus 2 SARS CoV 2 affects all patients regardless of age The incidence of venous thromboembolism in pediatric patients with SARS CoV 2 related illnesses is not well established Although deep vein thrombosis is rare in children in the absence of risk factors coagulopathy and the development of thromboses have been described in pediatric patients with acute COVID 19 and multisystem inflammatory syndrome This comprehensive review provides a detailed overview of SARS CoV 2 associated coagulopathy as well as strategies for optimizing the evaluation management and prevention of thrombosis in pediatric patients 0 |
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