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40 | or0rfxuu | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | How fast does the SARS-Cov-2 virus really mutate in heterogeneous populations? We introduce the problem of determining the mutational support of genes in the SARS-Cov-2 virus and estimating the distribution of mutations within different genes using small sample sizes that do not allow for accurate maximum likelihood estimation. The mutational support refers to the unknown number of sites mutated across all strains and individual samples of the SARS-Cov-2 genome; given the high cost and limited availability of real-time polymerase chain reaction (RT-PCR) test kits, especially in early stages of infections when only a small number of genomic samples (∼ 1000s) are available that do not allow for determining the exact degree of mutations in an RNA virus that comprises roughly 30, 000 nucleotides. Nevertheless, working with small sample sets is required in order to quickly predict the mutation rate of this and other viruses and get an insight into their transformational power. Furthermore, with the small number of samples available, it is hard to estimate the mutational landscape across different age/gender groups and geographical locations which may be of great importance in assessing different risk categories and factors influencing susceptibility to infection. To this end, we use our state-of-the art polynomial estimator techniques and the Good-Turing estimator to obtain estimates based on only roughly 1, 000 samples per category. Our analysis reveals an interesting finding: the mutational support appears to be statistically more significant in patients which appear to have lower infection rates and handle the exposure with milder symptoms, such as women and people of relatively young age (≤ 55). |
33 | 3zduon0f | What vaccine candidates are being tested for Covid-19? | Current research for a vaccine against Lassa hemorrhagic fever virus Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials. Here, we discuss several important aspects of LASV infection including immunobiology, immune evasion, and correlates of protection against LF, which have been identified through animal models and human infections. In addition, we discuss several vaccine candidates that have shown efficacy in animal models that could be advanced toward clinical trials. The increased fatality rate seen in the recent LASV outbreak in Nigeria highlights the importance of developing effective treatment and prevention strategies against LF. The spike in LASV cases seen in West Africa has the potential for increased mortality and human-to-human transmission, making the development and testing of effective vaccines for LASV critical. |
19 | 662pfa61 | what type of hand sanitizer is needed to destroy Covid-19? | Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 µM and 1.76 µM respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19. |
24 | ulmm28d5 | what kinds of complications related to COVID-19 are associated with diabetes | Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes() AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-four COVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P < 0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4(+) T lymphocyte counts in severe patients were lower than those in non-severe patients (P < 0.05). Logistic regression analysis identified decreased CD4(+) T lymphocyte counts (odds ratio [OR] = 0.988, 95%Confidence interval [95%CI] 0.979–0.997) and increased SAA levels (OR = 1.029, 95%CI 1.002–1.058) as risk factors for severity of COVID-19 with diabetes (P < 0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4(+) T lymphocyte counts and high SAA levels. |
9 | 7hvbbq15 | how has COVID-19 affected Canada | Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study BACKGROUND: The novel coronavirus disease 2019 (COVID-19) epidemic has spread from China to 25 countries. Local cycles of transmission have already occurred in 12 countries after case importation. In Africa, Egypt has so far confirmed one case. The management and control of COVID-19 importations heavily rely on a country's health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of COVID-19. METHODS: We used data on the volume of air travel departing from airports in the infected provinces in China and directed to Africa to estimate the risk of importation per country. We determined the country's capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing most to their risk. FINDINGS: Countries with the highest importation risk (ie, Egypt, Algeria, and South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (ie, Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya) have variable capacity and high vulnerability. We identified three clusters of countries that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and the city of Beijing, respectively. INTERPRETATION: Many countries in Africa are stepping up their preparedness to detect and cope with COVID-19 importations. Resources, intensified surveillance, and capacity building should be urgently prioritised in countries with moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Agence Nationale de la Recherche. |
28 | 50jgbtnr | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | SARS-CoV-2 in the ocular surface of COVID-19 patients The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, while the routes of transmission of this virus are still controversial. We enrolled 33 patients, without any ocular manifestation, with their ocular surface swabs collected for virus detection. RNA was detected strong positive in samples of both eyes from two patients. Therefore, SARS-CoV-2 may exist in the normal ocular surface of COVID-19 patients, suggesting that this virus might be spread through conjunctival contact. |
24 | vg48zqwz | what kinds of complications related to COVID-19 are associated with diabetes | Diabetes mellitus: Lessons from the COVID-19 pandemic |
26 | e8073l9p | what are the initial symptoms of Covid-19? | Coronavirus Disease 2019 (COVID-19): Protecting Hospitals From the Invisible Coronavirus disease 2019 (COVID-19) is optimized to spread widely: Its signs and symptoms are largely indistinguishable from those of other respiratory viruses. This commentary specifically addresses best ways to protect our hospitals against COVID-19. |
37 | 9oqzsd70 | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Molecular epidemiology of infectious bronchitis virus in Poland from 1980 to 2017 Abstract The presence of infectious bronchitis virus (IBV) was identified for the first time in the poultry population in Poland at the end of the 1960s. From this time a few waves of epidemics caused by different IBV variants spread across the country. In order to gain more insight into the molecular epidemiology of IBV in Poland, in the present study the S1 coding region of 34 IBV isolates and nearly whole genome of 10 strains collected over a period of 38 years was characterized. Phylogenetic analysis showed that these strains belonged to five recently established IBV lineages: GI-1, GI-12, GI-13, GI-19 and GI-23. Additionally, two strains from 1989 and 1997 formed a separate branch of the phylogenetic tree categorized as unique early Polish variants, and one strain was revealed to be the recombinant of these and GI-1 lineage viruses. Irrespective of year of isolation and S1-dependent genotype, the genome sequences of Polish IBV strains showed the presence of six genes and 13 ORFs: 5′UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′UTR, however their individual genes and putative proteins had different lengths. The phylogenetic analyses performed on the genome of ten Polish IBV strains revealed that they cluster into different groups. The Polish GI-1, GI-19 and GI-23 strains cluster with other similar viruses of these lineages, with the exception of the two strains from 1989 and 1997 which are different. It seems that in Poland in the 1980s and 1990s IBV strains with a unique genome backbone circulated in the field, which were then replaced by other strains belonging to other IBV lineages with a genome backbone specific to these lineages. The recombination analysis showed that some Polish strains resulted from a recombination event involving different IBV lineages, most frequently GI-13 and GI-19. |
4 | 2lk8vq03 | what causes death from Covid-19? | Top Concerns of Tweeters During the COVID-19 Pandemic: Infoveillance Study BACKGROUND: The recent coronavirus disease (COVID-19) pandemic is taking a toll on the world's health care infrastructure as well as the social, economic, and psychological well-being of humanity. Individuals, organizations, and governments are using social media to communicate with each other on a number of issues relating to the COVID-19 pandemic. Not much is known about the topics being shared on social media platforms relating to COVID-19. Analyzing such information can help policy makers and health care organizations assess the needs of their stakeholders and address them appropriately. OBJECTIVE: This study aims to identify the main topics posted by Twitter users related to the COVID-19 pandemic. METHODS: Leveraging a set of tools (Twitter's search application programming interface (API), Tweepy Python library, and PostgreSQL database) and using a set of predefined search terms ("corona," "2019-nCov," and "COVID-19"), we extracted the text and metadata (number of likes and retweets, and user profile information including the number of followers) of public English language tweets from February 2, 2020, to March 15, 2020. We analyzed the collected tweets using word frequencies of single (unigrams) and double words (bigrams). We leveraged latent Dirichlet allocation for topic modeling to identify topics discussed in the tweets. We also performed sentiment analysis and extracted the mean number of retweets, likes, and followers for each topic and calculated the interaction rate per topic. RESULTS: Out of approximately 2.8 million tweets included, 167,073 unique tweets from 160,829 unique users met the inclusion criteria. Our analysis identified 12 topics, which were grouped into four main themes: origin of the virus; its sources; its impact on people, countries, and the economy; and ways of mitigating the risk of infection. The mean sentiment was positive for 10 topics and negative for 2 topics (deaths caused by COVID-19 and increased racism). The mean for tweet topics of account followers ranged from 2722 (increased racism) to 13,413 (economic losses). The highest mean of likes for the tweets was 15.4 (economic loss), while the lowest was 3.94 (travel bans and warnings). CONCLUSIONS: Public health crisis response activities on the ground and online are becoming increasingly simultaneous and intertwined. Social media provides an opportunity to directly communicate health information to the public. Health systems should work on building national and international disease detection and surveillance systems through monitoring social media. There is also a need for a more proactive and agile public health presence on social media to combat the spread of fake news. |
9 | 5242ns8i | how has COVID-19 affected Canada | COVID-19: Modelling Local Transmission and Morbidity effects to provide an estimate of overall Relative Healthcare Resource Impact by General Practice Granularity Introduction Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the name given to the 2019 novel coronavirus. COVID-19 is the name given to the disease associated with the virus. SARS-CoV-2 is a new strain of coronavirus that has not been previously identified in humans. Methods Two key factors were analysed which when multiplied together would give an estimate of relative demand on healthcare utilisation. These factors were case incidence and case morbidity. GP Practice data was used as this provided the most geographically granular source of published public population data. To analyse case incidence, the latest values for indicators that could be associated with infection transmission rates were collected from the Office of National Statistics (ONS) and Quality Outcome Framework (QOF) sources. These included population density, % age >16 at fulltime work/education, % age over 60, % BME ethnicity, social deprivation as IMD 2019, Location as latitude/longitude, and patient engagement as % self-confident in their own long term condition management. Average case morbidity was calculated by applying the international mortality Odds Ratio to the local population relevant age and disease prevalences and then summing and dividing by the equivalent national figure. To provide a comparative measure of overall healthcare resource impact, individual GP practice impact scores were compared against the median practice. Results The case incidence regression is a dynamic situation with the significance of specific factors moderating over time as the balance between external infection, community transmission and impact of mitigation measures feeds through to the number of cases. It showed that currently Urban, % Working and age >60 were the strongest determinants of case incidence. The local population comorbidity remains unchanged. The range of relative HC impact was wide with 80% of practices falling between 20%-250% of the national median. Once practice population numbers were included it showed that the top 33% of GP practices supporting 45% of the patient population would require 68% of COVID-19 healthcare resources. The model provides useful information about the relative impact of Covid-19 on healthcare workload at GP practice granularity in all parts of England. Conclusion Covid-19 is impacting on the utilisation of health and social care resources across the country. This model provides a method for predicting relative local levels of disease burden based on defined criteria and thereby providing a method for targeting limited (and perhaps soon to be scarce) care resources to optimise national, regional and local responses to the COVID-19 outbreak. |
10 | in3pyyue | has social distancing had an impact on slowing the spread of COVID-19? | Effects of Government Mandated Social Distancing Measures on Cumulative Incidence of COVID-19 in the United States and its Most Populated Cities COVID-19, caused by the SARS-CoV-2 virus, has quickly spread throughout the world, necessitating assessment of the most effective containment methods. Very little research exists on the effects of social distancing measures on this pandemic. The purpose of this study was to examine the effects of government implemented social distancing measures on the cumulative incidence rates of COVID-19 in the United States on a state level, and in the 25 most populated cities, while adjusting for socio-demographic risk factors. The social distancing variables assessed in this study were: days to closing of non-essential business; days to stay home orders; days to restrictions on gathering, days to restaurant closings and days to school closing. Using negative binomial regression, adjusted rate ratios and 95% confidence intervals were calculated comparing two levels of a binary variable: above median value, and median value and below for days to implementing a social distancing measure. For city level data, the effects of these social distancing variables were also assessed in high (above median value) vs low (median value and below) population density cities. For the state level analysis, days to school closing was associated with cumulative incidence, with an adjusted rate ratio of 1.59 (95% CI:1.03,2.44), p=0.04 at 35 days. Some results were counterintuitive, including inverse associations between cumulative incidence and days to closure of non-essential business and restrictions on gatherings. This finding is likely due to reverse causality, where locations with slower growth rates initially chose not to implement measures, and later implemented measures when they absolutely needed to respond to increasing rates of infection. Effects of social distancing measures seemed to vary by population density in cities. Our results suggest that the effect of social distancing measures may differ between states and cities and between locations with different population densities. States and cities need individual approaches to containment of an epidemic, with an awareness of their own structure in terms of crowding and socio-economic variables. In an effort to reduce infection rates, cities may want to implement social distancing in advance of state mandates. |
11 | 33wbu4p2 | what are the guidelines for triaging patients infected with coronavirus? | Providing quality end-of-life care to older people in the era of COVID-19: perspectives from five countries |
47 | 1ku828xn | what are the health outcomes for children who contract COVID-19? | The clinical spectrum of encephalitis in COVID-19 disease: the ENCOVID multicentre study Background: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes yet. Objective: to describe the clinical phenotype, laboratory and neuroimaging findings of encephalitis associated with SARS-CoV-2 infection, their relationship with respiratory function and inflammatory parameters and their clinical course and response to treatment. Design: The ENCOVID multicentre study was carried out in 13 centres in northern Italy between February 20th and May 31st, 2020. Only patients with altered mental status and at least two supportive criteria for encephalitis with full infectious screening, CSF, EEG, MRI data and a confirmed diagnosis of SARS-CoV-2 infection were included. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded. Results: Out of 45 cases screened, twenty-five cases of encephalitis positive for SARS-CoV-2 infection with full available data were included. The most common symptoms at onset were delirium (68%), aphasia/dysarthria (24%) and seizures (24%). CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis. Conclusions and relevance: We found a wide clinical spectrum of encephalitis associated with COVID19 infection, underlying different pathophysiological mechanisms. Response to treatment and final outcome strongly depended on specific CNS-manifestations. |
6 | f3ds1rq6 | what types of rapid testing for Covid-19 have been developed? | Assessing the interactions between COVID-19 and influenza in the United States The 2019–2020 influenza sentinel surveillance data exhibits unexpected trends. Typical influenza seasons have a small herald wave, followed by a decrease due to school closure during holidays, and then a main post-holiday peak that is significantly larger than the pre-holiday wave. During the 2019–2020 influenza season, influenza-like illness data in the United States appears to have a markedly lower main epidemic peak compared to what would be expected based on the pre-holiday peak. We hypothesize that the 2019–2020 influenza season does have a lower than expected burden and that this deflation is due to a behavioral or ecological interaction with COVID-19. We apply an intervention analysis to assess if this influenza season deviates from expectations, then we compare multiple hypothesized drivers of the decrease in influenza in a spatiotemporal regression model. Lastly, we develop a mechanistic metapopulation model, incorporating transmission reduction that scales with COVID-19 risk perception. We find that the 2019–2020 ILI season is smaller and decreases earlier than expected based on prior influenza seasons, and that the increase in COVID-19 risk perception is associated with this decrease. Additionally, we find that a 5% average reduction in transmission is sufficient to reproduce the observed flu dynamics. We propose that precautionary behaviors driven by COVID-19 risk perception or increased isolation driven by undetected COVID-19 spread dampened the influenza season. We suggest that when surveillance for a novel pathogen is limited, surveillance streams of co-circulating infections may provide a signal. |
46 | k5k7hafn | what evidence is there for dexamethasone as a treatment for COVID-19? | COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and case–control study BACKGROUND: The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19. METHODS: We did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case–control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period. FINDINGS: Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55–76] years vs 57 [49–67] years; p=0·0010) and more likely to have arterial hypertension (33 [51%] vs 14 [27%] patients; odds ratio [OR] 2·8 [95% CI 1·3–6·1]; p=0·031) and obesity (11 [17%] vs 1 [2%]; OR 11·0 [1·3–83·4]; p=0·0059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78·8 years [IQR 75·3–81·3] vs 65·5 years [53·3–74·0]; p=0·0002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case–control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died during the study period. INTERPRETATION: In this cohort of patients with rheumatic and musculoskeletal diseases in a geographical region with a high prevalence of COVID-19, a poor outcome from COVID-19 seems to be associated with older age and the presence of comorbidities rather than the type of rheumatic disease or the degree of pharmacological immunosuppression. FUNDING: None. |
7 | 7vrm081c | are there serological tests that detect antibodies to coronavirus? | The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19 Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus. |
1 | jtsxpjhc | what is the origin of COVID-19 | Clinical features and laboratory inspection of novel coronavirus pneumonia (COVID-19) in Xiangyang, Hubei Background: Since December 2019, a novel coronavirus pneumonia (COVID-19) rapidly spread in China, reached multiple continents currently.We aimed to reveal the infectious characteristics of COVID-19 that provide more information for the research of novel coronavirus. Methods: We performed a retrospective study on the clinical characteristics of 128 COVID-19 cases with laboratory-confirmed from Xiangyang No 1 Hospitalad during January 2020 to 16 February 2020. Results: Female patients account for 53.1%. The aged below 20 years that accounts for 1.6% of overall patients. The aged in 21~50, 51~65, over 66 years were accounts for 44.5%, 35.1%,18.8%, respectively. In the difference age spectrum, all severe groups compared with non-severe groups were difference significantly ( P < 0.01 ). Fever ( 89.8% ) and Cough ( 67.2% ) were common clinical symptoms. The rate of patients with sore throats (14.1%) was rare. The rate of chest computed tomography scan showing ground glass opacity in overall, non-severe, severe groups were 63.3%, 60.7%, 76.2%, respectively. White blood cell counts in the normal range of overall patients, but severe group patients were increased significantly ( P < 0.01). Lymphocytes of overall patients were decreased. Alanine transaminase (ALT) and aspartate transaminase (AST) in the normal range of overall patients, but its were elevated in the severe group. Creatinine (CR) and blood urea nitrogen (BUN) of overall patients in the normal range. C-reactive protein (CRP) level of all patients were increased markedly, but it in the severe group was significantly higher than that in the non-severe group ( P < 0.01 ). Conclusions: Our data provide more information that advanced age, lower lymphocytes levels at the diagnosed COVID-19 patients may be a risk factor for unfavourable prognosis. The white blood cells and C-reactive protein level elevated in severe COVID-19 patients may be accompanying bacterial infection. 2019-nCov may be carries a risk factor of impaired liver and kidney function. |
21 | 4591ewsa | what are the mortality rates overall and in specific populations | Depletion of Alveolar Macrophages Ameliorates Virus-Induced Disease following a Pulmonary Coronavirus Infection Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1) is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM) in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality. |
25 | unnrflmr | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Broad-spectrum coronavirus antiviral drug discovery Introduction: The highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are lethal zoonotic viruses that have emerged into human populations these past 15 years. These coronaviruses are associated with novel respiratory syndromes that spread from person-to-person via close contact, resulting in high morbidity and mortality caused by the progression to Acute Respiratory Distress Syndrome (ARDS). Areas covered: The risks of re-emergence of SARS-CoV from bat reservoir hosts, the persistence of MERS-CoV circulation, and the potential for future emergence of novel coronaviruses indicate antiviral drug discovery will require activity against multiple coronaviruses. In this review, approaches that antagonize viral nonstructural proteins, neutralize structural proteins, or modulate essential host elements of viral infection with varying levels of efficacy in models of highly pathogenic coronavirus disease are discussed. Expert opinion: Treatment of SARS and MERS in outbreak settings has focused on therapeutics with general antiviral activity and good safety profiles rather than efficacy data provided by cellular, rodent, or nonhuman primate models of highly pathogenic coronavirus infection. Based on lessons learned from SARS and MERS outbreaks, lack of drugs capable of pan-coronavirus antiviral activity increases the vulnerability of public health systems to a highly pathogenic coronavirus pandemic. |
12 | rzr8qjw8 | what are best practices in hospitals and at home in maintaining quarantine? | Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing. |
16 | xsxt0tr9 | how long does coronavirus remain stable on surfaces? | Inactivation of Viruses on Surfaces by Ultraviolet Germicidal Irradiation In many outbreaks caused by viruses, the transmission of the agents can occur through contaminated environmental surfaces. Because of the increasing incidence of viral infections, there is a need to evaluate novel engineering control methods for inactivation of viruses on surfaces. Ultraviolet germicidal irradiation (UVGI) is considered a promising method to inactivate viruses. This study evaluated UVGI effectiveness for viruses on the surface of gelatin-based medium in a UV exposure chamber. The effects of UV dose, viral nucleic acid type (single-stranded RNA, ssRNA; single-stranded DNA, ssDNA; double-stranded RNA, dsRNA; and double-stranded DNA, dsDNA), and relative humidity on the virus survival fraction were investigated. For 90% viral reduction, the UV dose was 1.32 to 3.20 mJ/cm(2) for ssRNA, 2.50 to to 4.47 mJ/cm(2) for ssDNA, 3.80 to 5.36 mJ/cm(2) for dsRNA, and 7.70 to 8.13 mJ/cm(2) for dsDNA. For all four tested viruses, the UV dose for 99% viral reduction was 2 times higher than those for 90% viral reduction. Viruses on a surface with single-stranded nucleic acid (ssRNA and ssDNA) were more susceptible to UV inactivation than viruses with double-stranded nucleic acid (dsRNA and dsDNA). For the same viral reduction, the UV dose at 85% relative humidity (RH) was higher than that at 55% RH. In summary, results showed that UVGI was an effective method for inactivation of viruses on surfaces. |
15 | l0d87nck | how long can the coronavirus live outside the body | Immunity after natural exposure to enteric canine coronavirus does not provide complete protection against infection with the new pantropic CB/05 strain Abstract Recently, an outbreak of fatal infection caused by a pantropic variant (strain CB/05) of canine coronavirus (CCoV) has been reported. In this study, evidence is provided that immunity induced by natural exposure to enteric CCoV is not fully protective against strain CB/05. Twenty-two, 10-week-old beagles with a recent natural infection by enteric CCoV were randomly distributed in two experimental groups of eight (groups A and B) and one control group of six (group C) dogs. Dogs in groups A and B were inoculated oronasally with different doses (4×105 or 4×103 TCID50) of the pantropic strain CB/05, whereas dogs in group C were used as negative controls. Clinical, post-mortem and virological investigations showed that, despite the high serum antibody titres induced by the prior natural infection with enteric CCoV, dogs were susceptible to experimental infection with strain CB/05. This was shown by the occurrence of faecal shedding, and dogs displaying moderate clinical signs, mainly vomiting and diarrhoea. Involvement of the lymphoid tissues was evident as demonstrated by the acute lymphopenia (below 70% of the initial counts), gross lesions in spleen and lymph nodes and detection of CB/05 RNA in thymus, spleen and lymph nodes of some infected dogs. The presence of viral RNA in lymphoid tissues was observed only in dogs euthanised in the early stages of infection and the clinical course of the infection was unrelated to the viral dose administered. The present study demonstrates that strain CB/05 is able to induce infection and disease in dogs seropositive to enteric CCoV, thus highlighting the need for extensive epidemiological investigation and for the possible development of novel antigenically relevant vaccines. |
11 | o1agipos | what are the guidelines for triaging patients infected with coronavirus? | Implementation strategies to improve preconception and antenatal care for tobacco smoking, alcohol consumption and weight management: a systematic review protocol. BACKGROUND Despite existing best practice care recommendations for addressing tobacco smoking, alcohol consumption and weight management in preconception and antenatal care, such recommendations are often not implemented into routine practice. Effective strategies that target known barriers to implementation are key to reducing this evidence to practice gap. The aim of this review is to synthesise the evidence on the effectiveness of implementation strategies in improving the provision of preconception and antenatal care for these modifiable risk factors. METHODS Randomised and non-randomised study designs will be eligible for inclusion if they have a parallel control group. We will include studies that either compare an implementation strategy to usual practice or compare two or more strategies. Participants may include any health service providing preconception or antenatal care to women and/or the health professionals working within such a service. The primary outcome will be any measure of the effectiveness of implementation strategies to improve preconception and/or antenatal care for tobacco smoking, alcohol consumption and/or weight management (including care to improve nutrition and/or physical activity). Secondary outcomes will include the effect of the implementation strategy on women's modifiable risk factors, estimates of absolute costs or cost-effectiveness and any reported unintentional consequences. Eligible studies will be identified via searching Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Maternity and Infant Care, CINAHL, ProQuest Dissertations and Theses and other sources (e.g. contacting experts in the field). Study selection, data extraction and risk of bias will be assessed independently by two review authors and differences resolved by a third reviewer. If data permits, we will conduct fixed-effects or random-effects meta-analysis where appropriate. If studies do not report the same outcome or there is significant heterogeneity, results will be summarised narratively. DISCUSSION This review will identify which implementation strategies are effective in improving the routine provision of preconception and antenatal care for tobacco smoking, alcohol consumption and weight management. Such a review will be of interest to service providers, policy makers and implementation researchers seeking to improve women's modifiable risk factors in preconception and antenatal care settings. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019131691. |
11 | ksiaulkd | what are the guidelines for triaging patients infected with coronavirus? | Digital triage for people with multiple sclerosis in the age of COVID-19 pandemic We propose a possible approach for the remote monitoring of infection risk in people with multiple sclerosis, especially those on immunosuppressant drugs, during COVID-19 pandemic. We developed a digital triage tool to be sent to patients to quickly identify people with high risk of COVID-19 infection. This tool will also limit unnecessary accesses to the MS centers reducing the risk of spreading the infection. |
11 | x64tii2t | what are the guidelines for triaging patients infected with coronavirus? | COVID-19 pandemic – A focused review for clinicians Abstract Background The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics and society. A wealth of data has been generated since its emergence in December 2019 and it is vital for clinicians to keep up with this data from across the world at a time of uncertainty and constantly evolving guidelines and clinical practice. Objectives Here we provide an update for clinicians on the recent developments about virology, diagnostics, clinical presentation, viral shedding, and treatment options for COVID-19 based on current literature. Sources We considered published peer-reviewed papers and non-peer-reviewed pre-print manuscripts on COVID19 and related aspects with an emphasis on clinical management aspects. Content We describe the virological characteristics of SARS-CoV-2 and clinical course of COVID-19 with an emphasis on diagnostic challenges, duration of viral shedding, severity markers and current treatment options. Implications The key challenge in managing COVID-19 remains the patient density. However, accurate diagnoses as well as early identification and management of high-risk severe cases are important for many clinicians. For improved management of cases, there is a need to understand test probability of serology, qRT-PCR and radiological testing, and the efficacy of available treatment options that could be used in severe cases with a high risk of mortality. |
6 | xfjexm5b | what types of rapid testing for Covid-19 have been developed? | Impact of self-imposed prevention measures and short-term government intervention on mitigating and delaying a COVID-19 epidemic Background: With new cases of COVID-19 surging around the world, many countries have to prepare for moving beyond the containment phase. Prediction of the effectiveness of non-case-based interventions for mitigating, delaying or preventing the epidemic is urgent, especially for countries affected by the ongoing seasonal influenza activity. Methods: We developed a transmission model to evaluate the impact of self-imposed prevention measures (handwashing, mask-wearing, and social distancing) due to the spread of COVID-19 awareness and of short-term government-imposed social distancing on the peak number of diagnoses, attack rate and time until the peak number of diagnoses. Findings: For fast awareness spread in the population, self-imposed measures can significantly reduce the attack rate, diminish and postpone the peak number of diagnoses. A large epidemic can be prevented if the efficacy of these measures exceeds 50%. For slow awareness spread, self-imposed measures reduce the peak number of diagnoses and attack rate but do not affect the timing of the peak. Early implementation of short-term government interventions can only delay the peak (by at most 7 months for a 3-month intervention). Interpretation: Handwashing, mask-wearing and social distancing as a reaction to information dissemination about COVID-19 can be effective strategies to mitigate and delay the epidemic. We stress the importance of rapidly spreading awareness on the use of these self-imposed prevention measures in the population. Early-initiated short-term government-imposed social distancing can buy time for healthcare systems to prepare for an increasing COVID-19 burden. Keywords: SARS-CoV-2, COVID-19, mathematical model, prevention measures, mitigation, epidemic control, disease awareness, social distancing, handwashing, mask-wearing |
44 | s00gvgwx | How much impact do masks have on preventing the spread of the COVID-19? | The 2003 SARS outbreak and its impact on infection control practices Summary Severe Acute Respiratory Syndrome (SARS) emerged recently as a new infectious disease that was transmitted efficiently in the healthcare setting and particularly affected healthcare workers (HCWs), patients and visitors. The efficiency of transmission within healthcare facilities was recognised following significant hospital outbreaks of SARS in Canada, China, Hong Kong, Singapore, Taiwan and Vietnam. The causative agent of SARS was identified as a novel coronavirus, the SARS coronavirus. This was largely spread by direct or indirect contact with large respiratory droplets, although airborne transmission has also been reported. High infection rates among HCWs led initially to the theory that SARS was highly contagious and the concept of 'super-spreading events'. Such events illustrated that lack of infection control (IC) measures or failure to comply with IC precautions could lead to large-scale hospital outbreaks. SARS was eventually contained by the stringent application of IC measures that limited exposure of HCWs to potentially infectious individuals. As the 'global village' becomes smaller and other microbial threats to health emerge, or re-emerge, there is an urgent need to develop a global strategy for infection control in hospitals. This paper provides an overview of the main IC practices employed during the 2003 SARS outbreak, including management measures, dedicated SARS hospitals, personal protective equipment, isolation, handwashing, environmental decontamination, education and training. The psychological and psychosocial impact on HCWs during the outbreak are also discussed. Requirements for IC programmes in the post-SARS period are proposed based on the major lessons learnt from the SARS outbreak. |
15 | 52c4xhiw | how long can the coronavirus live outside the body | Infections nosocomiales à coronavirus humains chez le nouveau-né 1 Travail financé en partie par la Société française de pédiatrie (bourse de DEA), le ministère de la santé (PHRC 97) et le CCLIN–Ouest. A. Gagneur est boursier de la Société française de pédiatrie. Résumé Les coronavirus humains sont des virus enveloppés à ARN de la famille des Coronaviridae avec deux sérogroupes identifiés : 229-E et OC-43. Ces virus possèdent le plus grand ARN viral connu. Ce génome est un ARN simple brin positif associé à une protéine phosphorylée de la nucléocapside, la protéine N. L'enveloppe des coronavirus humains contient deux ou trois glycoprotéines membranaires : S ou spike protein, M ou protéine de membrane et HE ou hémagglutine-estérase. Le rôle pathogène de ces virus est mal connu en raison des difficultés diagnostiques. Cependant la mise au point de l'immunofluorescence avec anticorps monoclonaux et des techniques d'amplification génique permet de nouvelles recherches épidémiologiques. Les coronavirus peuvent survivre jusqu'à six jours en suspension et trois heures après séchage, ce qui suggère un rôle nosocomial potentiel. Deux études prospectives réalisées dans une unité de réanimation néonatale et pédiatrique ont révélé une relation significative entre l'existence de prélèvement nasopharyngés positifs et la survenue de symptômes respiratoires. Des prélèvements positifs chez le personnel suggèrent une contamination patient-personnel ou personnel–patient. En raison de leur survie possible sur les surfaces et de l'efficacité démontrée des agents désinfectants, des mesures universelles de prévention associant lavage des mains et désinfection des surfaces peuvent être proposées. Abstract Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive naso-pharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission. |
15 | z0l81bzx | how long can the coronavirus live outside the body | Detection of air and surface contamination by SARS-CoV-2 in hospital rooms of infected patients Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ(2) test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1–4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2. |
33 | x64tii2t | What vaccine candidates are being tested for Covid-19? | COVID-19 pandemic – A focused review for clinicians Abstract Background The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics and society. A wealth of data has been generated since its emergence in December 2019 and it is vital for clinicians to keep up with this data from across the world at a time of uncertainty and constantly evolving guidelines and clinical practice. Objectives Here we provide an update for clinicians on the recent developments about virology, diagnostics, clinical presentation, viral shedding, and treatment options for COVID-19 based on current literature. Sources We considered published peer-reviewed papers and non-peer-reviewed pre-print manuscripts on COVID19 and related aspects with an emphasis on clinical management aspects. Content We describe the virological characteristics of SARS-CoV-2 and clinical course of COVID-19 with an emphasis on diagnostic challenges, duration of viral shedding, severity markers and current treatment options. Implications The key challenge in managing COVID-19 remains the patient density. However, accurate diagnoses as well as early identification and management of high-risk severe cases are important for many clinicians. For improved management of cases, there is a need to understand test probability of serology, qRT-PCR and radiological testing, and the efficacy of available treatment options that could be used in severe cases with a high risk of mortality. |
4 | jir7n19b | what causes death from Covid-19? | Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China Rationale: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease. Objectives: To study the epidemiology, clinical features and outcomes of patients with COVID-19. Methods: we performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital. Measurements and Main Results: The median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%. Conclusions: The COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes. Keywords: coronavirus disease 2019; clinical features; outcomes; severe patients |
28 | ddqxzcnt | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Model informed dosing of Hydroxycholoroquine in COVID-19 patients: Learnings from the recent experience, remaining uncertainties and Gaps AIMS: In the absence of a commonly agreed dosing protocol based on pharmacokinetic considerations, the dose and treatment duration for hydroxychloroquine (HCQ) COVID-19 disease currently vary across national guidelines and clinical study protocols. We have used a model-based approach to explore the relative impact of alternative dosing regimens proposed in different dosing protocols for hydroxychloroquine in COVID-19. METHODS: We compared different PK exposures using Monte Carlo simulations based on a previously published population pharmacokinetic model in patients with rheumatoid arthritis, externally validated using both independent data in lupus erythematous patients and recent data in French COVID-19 patients. Clinical efficacy and safety information from COVID-19 patients treated with HCQ were used to contextualize and assess the actual clinical value of the model predictions. RESULTS: Literature and observed clinical data confirm the variability in clinical responses in COVID-19 when treated with the same fixed doses. Confounding factors were identified that should be taken into account for dose recommendation. For 80% of patients, doses higher than 800mg day on D1 followed by 600mg daily on following days might not be needed for being cured. Limited adverse drug reactions have been reported so far for this dosing regimen, most often confounded by co-medications, comorbidities or underlying COVID-19 disease effects. CONCLUSION: Our results were clear indicating the unmet need for characterization of target PK exposures to inform HCQ dosing optimization in COVID-19. Dosing optimization for HCQ in COVID-19 is still an unmet need. Efforts in this sense are a prerequisite for best the benefit/risk balance. |
33 | cvk39tih | What vaccine candidates are being tested for Covid-19? | 2018 ACCP Global Conference on Clinical Pharmacy: October 20–23, 2018 |
36 | 2bzllo0n | What is the protein structure of the SARS-CoV-2 spike? | Programmed 'disarming' of the neutrophil proteome reduces the magnitude of inflammation The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation. |
8 | cmaw7jcn | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Practical insights for paediatric otolaryngology surgical cases and performing microlaryngobronchoscopy during the COVID-19 pandemic Abstract Paediatric otolaryngology practice involves examining and operating in anatomical locations with high levels of aerosol generation and transmission of COVID-19 to treating clinicians, especially from the asymptomatic patient populations including children. During the COVID-19 pandemic all emergent otolaryngological conditions affecting the airway, oral, and nasal cavities should be managed medically where possible and any operating deferred. We present guidelines for operating on paediatric otolaryngological patients when necessary during the COVID-19 pandemic, and incorporate experience gathered during microlaryngobronchoscopy on a COVID-19 positive infant at our institution. |
39 | 5rfxis6f | What is the mechanism of cytokine storm syndrome on the COVID-19? | Vitamin D Receptor stimulation to reduce Acute Respiratory Distress Syndrome (ARDS) in patients with Coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166 Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months. |
12 | shymfs4i | what are best practices in hospitals and at home in maintaining quarantine? | Restructured society and environment: A review on potential technological strategies to control the COVID-19 pandemic Abstract The emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in China at December 2019 had led to a global outbreak of coronavirus disease 2019 (COVID-19) and the disease started to spread all over the world and became an international public health issue. The entire humanity has to fight in this war against the unexpected and each and every individual role is important. Healthcare system is doing exceptional work and the government is taking various measures that help the society to control the spread. Public, on the other hand, coordinates with the policies and act accordingly in most state of affairs. But the role of technologies in assisting different social bodies to fight against the pandemic remains hidden. The intention of our study is to uncover the hidden roles of technologies that ultimately help for controlling the pandemic. On investigating, it is found that the strategies utilizing potential technologies would yield better benefits and these technological strategies can be framed either to control the pandemic or to support the confinement of the society during pandemic which in turn aids in controlling the spreading of infection. This study enlightens the various implemented technologies that assists the healthcare systems, government and public in diverse aspects for fighting against COVID-19. Furthermore, the technological swift that happened during the pandemic and their influence in the environment and society is discussed. Besides the implemented technologies, this work also deals with untapped potential technologies that have prospective applications in controlling the pandemic circumstances. Alongside the various discussion, our suggested solution for certain situational issues is also presented. |
25 | wrxt6qqp | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Biomarkers of sepsis: clinically useful? PURPOSE OF REVIEW The purpose of this review is to indicate recent developments in biomarkers of sepsis and to evaluate their impact on clinical use. According to the 'surviving sepsis campaign,' diagnosis of sepsis and infection is urgent; early and specific treatment is most effective to reduce complications and to decrease mortality. RECENT FINDINGS A variety of biomarkers of sepsis is presently available. The diagnostic spectrum of the various markers, however, is different. Some primarily indicate severity of inflammation (e.g. interleukin-6), others respond to infection, but do not indicate the host response well (endotoxin, lipoprotein binding protein, triggering receptor on myeloid cells). There are new markers with limited clinical experience, for example triggering receptor on myeloid cells or mid-pro atrial natriuretic peptide (Seristra, Brahms AG, Hennigsdorf, Germany). Procalcitonin is a well-established biomarker of sepsis that fulfills several criteria of clinical needs: it responds both to infection and severity of inflammation and thus has an impact on therapy. Recent studies indicate that antibiotic treatment can also be guided by procalcitonin. Further indications, including diagnosis of invasive bacterial infections and diagnosis of sepsis in neonates and children have been reported recently. SUMMARY Recent data and cumulative analyses indicate that biomarkers of sepsis improve diagnosis of sepsis. However, only a few markers have impact on therapy and fulfill the clinical requirements. Procalcitonin is a well-established marker, indicating infection, sepsis, and progression to the more severe stages of the disease. Today, this biomarker should be in the diagnostic portfolio of an intensive care unit or emergency ward. |
50 | ojs5e7n9 | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2. |
7 | covnpc8z | are there serological tests that detect antibodies to coronavirus? | A novel coronavirus capable of lethal human infections: an emerging picture SUMMARY: In September 2012, a novel coronavirus was isolated from a patient in Saudi Arabia who had died of an acute respiratory illness and renal failure. The clinical presentation was reminiscent of the outbreak caused by the SARS-coronavirus (SARS-CoV) exactly ten years ago that resulted in over 8000 cases. Sequence analysis of the new virus revealed that it was indeed a member of the same genus as SARS-CoV. By mid-February 2013, 12 laboratory-confirmed cases had been reported with 6 fatalities. The first 9 cases were in individuals resident in the Middle East, while the most recent 3 cases were in family members resident in the UK. The index case in the UK family cluster had travel history to Pakistan and Saudi Arabia. Although the current evidence suggests that this virus is not highly transmissible among humans, there is a real danger that it may spread to other parts of the world. Here, a brief review of the events is provided to summarize the rapidly emerging picture of this new virus. |
44 | rndu5ake | How much impact do masks have on preventing the spread of the COVID-19? | Using rapid online surveys to assess perceptions during infectious disease outbreaks: a cross-sectional survey on Covid-19 among the general public in the United States and United Kingdom Background: Given the extensive time needed to conduct a nationally representative household survey and the commonly low response rate in phone surveys, rapid online surveys may be a promising method to assess and track knowledge and perceptions among the general public during fast-moving infectious disease outbreaks. Objective: To apply rapid online surveying to determine knowledge and perceptions of coronavirus disease 2019 (Covid-19) among the general public in the United States (US) and the United Kingdom (UK). Methods: An online questionnaire was administered to 3,000 adults residing in the US and 3,000 adults residing in the UK who had registered with Prolific Academic to participate in online research. Strata by age (18 - 27, 28 - 37, 38 - 47, 48 - 57, or >=58 years), sex (male or female), and ethnicity (White, Black or African American, Asian or Asian Indian, Mixed, or "Other"), and all permutations of these strata, were established. The number of participants who could enrol in each of these strata was calculated to reflect the distribution in the US and UK general population. Enrolment into the survey within the strata was on a first-come, first-served basis. Participants completed the questionnaire between February 23 and March 2 2020. Results: 2,986 and 2,988 adults residing in the US and the UK, respectively, completed the questionnaire. 64.4% (1,924/2,986) of US and 51.5% (1,540/2,988) of UK participants had a tertiary education degree. 67.5% (2,015/2,986) of US participants had a total household income between $20,000 and $99,999, and 74.4% (2,223/2,988) of UK participants had a total household income between GBP15,000 and GBP74,999. US and UK participants' median estimate for the probability of a fatal disease course among those infected with SARS-CoV-2 was 5.0% (IQR: 2.0% - 15.0%) and 3.0% (IQR: 2.0% - 10.0%), respectively. Participants generally had good knowledge of the main mode of disease transmission and common symptoms of Covid-19. However, a substantial proportion of participants had misconceptions about how to prevent an infection and the recommended care-seeking behavior. For instance, 37.8% (95% CI: 36.1% - 39.6%) of US and 29.7% (95% CI: 28.1% - 31.4%) of UK participants thought that wearing a common surgical mask was 'highly effective' in protecting them from acquiring Covid-19. 25.6% (95% CI: 24.1% - 27.2%) of US and 29.6% (95% CI: 28.0% - 31.3%) of UK participants thought it prudent to refrain from eating at Chinese restaurants. Around half (53.8% [95% CI: 52.1% - 55.6%] of US and 39.1% [95% CI: 37.4% - 40.9%] of UK participants) thought that children were at an especially high risk of death when infected with SARS-CoV-2. Conclusions: The distribution of participants by total household income and education followed approximately that of the general population. The findings from this online survey could guide information campaigns by public health authorities, clinicians, and the media. More broadly, rapid online surveys could be an important tool in tracking the public's knowledge and misperceptions during rapidly moving infectious disease outbreaks. |
15 | yk9u4fvp | how long can the coronavirus live outside the body | Perceptions of the Adult US Population regarding the Novel Coronavirus Outbreak Background: COVID-19 outbreak is spreading globally. Although the risk of infection in the US is currently low, it is important to understand the public perception of risk and trust in sources of information to better inform public health messaging. In this study, we surveyed the adult US population to understand their risk perceptions about the COVID-19 outbreak. Methods and Findings: We used an online platform to survey 718 adults in the US in early February 2020 using a questionnaire that we developed. Our sample was fairly similar to the general adult US population in terms of age, gender, race, ethnicity and education. We found that 69% of the respondents wanted the scientific/public health leadership (either the CDC Director or NIH Director) to lead the US response to COVID-19 outbreak as compared to 14% who wanted the political leadership (either the president or the Congress) to lead the response. Risk perception was low (median score of 5 out of 10) with the respondents trusting health professionals and health officials for information on COVID-19. Majority of the respondents were in favor of strict infection prevention policies to control the outbreak. Conclusion: Given our results, the public health/scientific leadership should be at the forefront of the COVID-19 response to promote trust. |
12 | qlm4949c | what are best practices in hospitals and at home in maintaining quarantine? | How up to date was this information? |
38 | 2vjy914c | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Expression of SARS-CoV-2 Receptor ACE2 and Coincident Host Response Signature Varies by Asthma Inflammatory Phenotype Abstract Background Over 300 million people carry a diagnosis of asthma with data to suggest they are at higher risk for infection or adverse outcomes from SARS-CoV-2. Asthma is remarkably heterogenous and it is currently unclear how patient intrinsic factors may relate to COVID-19. Objective Identify and characterize subsets of asthmatics at increased risk for SARS-CoV-2 infection. Methods Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to ACE2 expression within bronchial epithelium. ACE-2 correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. Results Stratifying by Type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the SARS-CoV-2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with Type 1 and 2 interferon signatures, normally induced by viral infections. T cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe COVID-19, including male sex, history of hypertension, low peripheral blood and elevated BAL lymphocytes. Conclusion ACE2 expression is linked to upregulation of viral response genes in a subset of Type-2 low asthmatics with characteristics resembling known risk factors for severe COVID-19. Therapies targeting the interferon family and T cell activating factors may therefore be of benefit in a subset of patients. Clinical Implication Type-2 low asthmatics may be at increased risk for adverse outcome from COVID-19 and deserve increased vigilance upon developing symptoms. |
22 | bhqtip9x | are cardiac complications likely in patients with COVID-19? | Cardiovascular Activity |
9 | bcocsjij | how has COVID-19 affected Canada | The prevalance of respiratory viruses among healthcare workers serving pilgrims in Makkah during the 2009 influenza A (H1N1) pandemic Summary Despite the high risk of acquiring respiratory infections, healthcare workers who treat pilgrims at Hajj have not been studied in previous research on respiratory diseases during Hajj. The objective of this study was to determine the prevalence of different respiratory viruses among healthcare workers who treated pilgrims during Hajj 2009, the year of the influenza A H1N1 pandemic. A cross-sectional study was performed just before and after Hajj (25–29 November, 2009). Nasal and throat swabs were tested for 18 respiratory virus types and subtypes. A total of 184 healthcare workers were examined. Most were men (85%) with an average age of 41 years. Before the Hajj, rates of seasonal influenza vaccination were higher (51%) than rates of pandemic influenza A H1N1 vaccination (22%). After the Hajj, participants reported high rates of maintaining hand hygiene (98%), cough etiquette (89%), and wearing a face mask (90%). Among all the viruses tested, only two were detected: rhinovirus was detected in 12.6% and Coronavirus 229E in 0.6%. Rhinovirus was detected in 21% of those who had respiratory symptoms during Hajj. Influenza A (including H1N1), influenza B. respiratory syncytial virus, other coronaviruses, parainfluenza viruses, human metapneumovirus, adenovirus, and human bocavirus were not detected. The finding of high rates of rhinovirus infection corresponds to their frequent occurrence in adults. None of the participants had influenza A H1N1 2009, possibly because it was also infrequent among the 2009 pilgrims. |
37 | n73o8i0w | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Access to Care for Dementia patients suffering from COVID-19 |
17 | 5uze06rp | are there any clinical trials available for the coronavirus | A phase 1 trial of nebulised heparin in acute lung injury INTRODUCTION: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. No human studies have been undertaken to date. We assessed the feasibility, safety and potential anticoagulant effects of administration of nebulised heparin to patients with ALI. METHODS: An open label phase 1 trial of four escalating doses of nebulised heparin was performed. A total of 16 ventilated patients with ALI were studied. The first group was administered a total of 50,000 U/day, the second group 100,000 U/day, the third group 200,000 U/day and the fourth group 400,000 U/day. Assessments of lung function included the PaO(2)/FiO(2 )ratio, lung compliance and the alveolar dead space fraction. Monitoring of anticoagulation included the activated partial thromboplastin time (APTT) and the thrombin clotting time. Bronchoalveolar lavage fluid was collected and the prothrombin fragment and tissue plasminogen activator levels were assessed. Analysis of variance was used to compare the effects of dose. RESULTS: No serious adverse events occurred for any dose. The changes over time for the PaO(2)/FiO(2 )ratio, lung compliance and the alveolar dead space fraction levels were similar for all doses. A trend to increased APTT and thrombin clotting time levels was present with higher doses (P = 0.09 and P = 0.1, respectively). For the highest dose, the APTT reached 64 seconds; following cessation of nebulised heparin, the APTT fell to 39 seconds (P = 0.06). In bronchoalveolar lavage samples a trend to reduced prothrombin fragment levels was present with higher doses (P = 0.1), while tissue plasminogen activator levels were similar for all doses. CONCLUSION: Administration of nebulised heparin to mechanically ventilated patients with ALI is feasible. Nebulised heparin was not associated with any serious adverse events, and at higher doses it increased APTT levels. Larger trials are required to further investigate the safety and efficacy of nebulised heparin. In these trials due consideration must be given to systemic anticoagulant effects. TRIAL REGISTRATION: Australian Clinical trials registry ACTRN12606000388516. |
32 | cr4yp5b7 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies. |
17 | 873kd1iu | are there any clinical trials available for the coronavirus | Coronavirus Disease 2019 and the Pediatric Gastroenterologist |
32 | d9v5xtx7 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV |
8 | 3e4mn5a8 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Prevalence and Clinical Presentation of Health Care Workers With Symptoms of Coronavirus Disease 2019 in 2 Dutch Hospitals During an Early Phase of the Pandemic IMPORTANCE: On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. OBJECTIVE: To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. MAIN OUTCOMES AND MEASURES: The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase–polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. RESULTS: Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. CONCLUSIONS AND RELEVANCE: Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently. |
50 | j6lbxlm3 | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | Covid-19: What do we know so far about a vaccine? |
18 | afh4j2ud | what are the best masks for preventing infection by Covid-19? | Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human CoVs. |
37 | cmx3q2sc | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Detection and phylogenetic characterization of astroviruses in insectivorous bats from Central‐Southern Italy In recent years, bats have been found to harbour many viruses, raising several questions about their role as reservoirs and potential disseminators of zoonotic viruses. We investigated the presence of six virus families in bats in three regions of Central‐Southern Italy. Astroviruses were identified in seven of 13 bat species. Sequence analysis revealed marked genetic heterogeneity among the astroviruses identified, with nucleotide identity ranging between 60.26% and 87.62%. Astrovirus diversity was not associated with the bat species, the geographic areas or the bat colony, suggesting the circulation of several astrovirus strains in Italian ecosystems. Genetic diversification and interspecies transmission appear common in bat astroviruses and could provide, potentially, the bases for transmission to humans and other mammals. Yet overemphasizing this risk might have detrimental consequences for bat conservation and preservation of the important ecosystem services bats provide. |
22 | nccim66e | are cardiac complications likely in patients with COVID-19? | Evidence-Based Medicine in the Intensive Care Unit |
20 | 3bt1ncgj | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Reply to: 'Interaction between RAAS inhibitors and ACE2 in the context of COVID-19' |
29 | 91krsxv6 | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | Research strategy of drugs against 2019-novel coronavirus based on supramolecular "qi chromatography" theory of TCM/ 基于中医药超分子"气析"理论探讨抗新型冠状病毒药物的研究策略 At present, the 2019-novel coronavirus (2019-nCoV) is rampant all over the country, and controlling the spread of its epidemic has become a top priority. It is very difficult to control the epidemic spreading because there is no specific drug to fight against it. Therefore, it is urgent task for us to develop a specific drug as soon as possible, and attracting worldwide attention. The studies on anti-2019-nCoV drugs were generally carried out in three modes, as vaccine, chemical drugs and traditional Chinese medicine (TCM). Because the developing on vaccines and chemicals takes too long, it is hard to solve the urgent problem. Moreover, the RNA of coronavirus has been recombined so quickly that the vaccines and drugs studied with great efforts not only may miss the epidemic time, but also cannot be used in the next generation of new coronavirus treatment, as a result that the work of epidemic prevention is formidable. However, the prescriptions from traditional Chinese medicine theory can cure the epidemic disease, but how to develop it into a specific drug with clear chemical composition and clear pharmacologic mechanism, is also an urgent problem to be solved. In this paper, the new coronavirus and its drug development are reviewed, while the advantages and disadvantages are analyzed, and the drug dilemma research phenomenon is clarified by using the supramolecular "qi chromatography" theory. It is suggested that the strategy of anti-coronavirus drug developing should be put forward based on the impact of "qi chromatography" of biological supramolecular "imprinting template", in order to develop new drugs against 2019-nCoV to control the spread of the epidemic as quick as we can, and establish a new research and development model of anti-coronavirus drug on integration of traditional Chinese and Western medicine, turning passive into active. |
24 | dwfb81aj | what kinds of complications related to COVID-19 are associated with diabetes | ECR 2012 Book of Abstracts - A - Postergraduate Educational Programme |
35 | kw8cg1uh | What new public datasets are available related to COVID-19? | COVID-19 pneumonia manifestations at the admission on chest ultrasound, radiographs, and CT: single-center study and comprehensive radiologic literature review PURPOSE: To investigate the imaging features of emerging COVID-19 pneumonia on chest ultrasound (US), radiographs (CXR) and computed tomography (CT) examinations performed at admission and to provide a comprehensive radiological literature review on ongoing radiological data from recent publications. MATERIALS AND METHODS: In this retrospective single-center study, we enrolled consecutive patients from February 15, 2020, to March 15, 2020, with laboratory-confirmed SARS-CoV-2 hospitalized in Valduce Hospital (Como, Italy). Multi-modality imaging findings were evaluated and compared. Literature research was conducted through a methodical search on Pubmed and Embase databases. RESULTS: Fifty-eight patients (36 men, 22 women; age range, 18–98 years) were included in the study. Among these, chest US, CXR, and CT were performed respectively in twenty-two, thirty-two and forty-two patients. Lung US findings were consistent with diffuse B lines (100%) and subpleural consolidations (27.3%). CXR showed prevalent manifestations of consolidations (46.9%) and hazy increased opacities (37.5%). Typical CT features included bilateral and multilobar ground-glass opacities (GGO) with (59.5%) and without (35.7%) consolidations having a predominantly peripheral distribution (64.3%). Other imaging features included crazy paving pattern (57.1%), fibrous stripes (50%), subpleural lines (35.7%), architectural distortion (28.6%), air bronchogram sign (26.2%), vascular thickening (23.8%) and nodules (2.4%). Also, enlarged lymph nodes (14.3 %) and pleural effusion (7.1%) were observed. The literature review identified twenty-six original studies supporting our imaging chest findings. CONCLUSION: The spectrum of chest imaging manifestations of COVID-19 pneumonia upon admission includes B-lines and consolidations on US, consolidations and hazy increased opacities on CXR, and multifocal GGO with consolidations on CT. |
14 | b3ui95vx | what evidence is there related to COVID-19 super spreaders | COVID-19: Melatonin as a potential adjuvant treatment Abstract This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death. Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation. |
38 | sym43q4k | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection The pathogenesis of viral infections involves an immune response by cytokines, causing a deleterious effect on organ function, in addition to tissue destruction due to viral replication. Clinical symptoms and laboratory findings of the human coronavirus disease COVID-19, caused by the novel coronavirus SARS CoV-2, indicate cytokine involvement. Our laboratory showed that an experimental murine coronavirus (MHV-A59) can be transmitted into the brain by intranasal or intracerebral exposure and that neurovirulence is mediated by cytokine secretion. In this study we investigated which cells in the brain produce cytokines, thus functioning as the brain's innate immune system. Using tissue cultures of microglia, and clonal populations of astrocytes, we found that microglia and type I astrocytes (but not types II and III), produced pro-inflammatory cytokines in response to MHV-A59 infection. A molecularly closely related, non-encephalitic strain of the virus (MHV-2) caused in vitro infection, but without cytokine induction. Furthermore, immunofluorescence and immunohistochemistry revealed that type I astrocytes and microglia have perivascular foot processes necessary for the formation of the perivascular glymphatic system, the anatomical site of the brain's innate immune system. Cytokine secretion by type I astrocytes and microglia, as part of the brain's glymphatic and innate immune system, contributes to the pathogenesis of an encephalitic coronavirus infection, and indicates the rationale for anti-cytokine therapies for COVID-19. |
32 | qxp0gfp3 | Does SARS-CoV-2 have any subtypes, and if so what are they? | Interferons Alpha, Beta, and Omega Interferon alpha (IFN-α) is a mixture of closely related proteins, termed "subtypes," expressed from distinct chromosomal genes. Interferon β (IFN-β) is a single protein species and is molecularly related to IFN-α subtypes, although it is antigenically distinct from them. IFN omega (IFN-ω) is antigenically distinct from IFN-α and IFN-β but is molecularly related to both. The genes of three IFN subtypes are tandemly arranged on the short arm of chromosome 9. They are transiently expressed following induction by various exogenous stimuli, including viruses. They are synthesized from their respective mRNAs for relatively short periods following gene activation and are secreted to act, via specific cell surface receptors, on other cells. IFN-α subtypes are secreted proteins and as such are transcribed from mRNAs as precursor proteins, pre-IFN-α, containing N-terminal signal polypeptides of 23 hydrophobic amino acids (aa) mainly. Pre-IFN-β contains 187 aa, of which 21 comprise the N-terminal signal polypeptide and 166 comprise the mature IFN-β protein. IFN-ω contains 195 aa—the N-terminal 23 comprising the signal sequence and the remaining 172, the mature IFN-ω protein. At the C-terminus, the aa sequence of IFN-ω is six residues longer than that of IFN-α or IFN-β proteins. IFN-α, as a mixture of subtypes, and IFN-ω may be produced together following viral infection of null lymphocytes or monocytes/macrophages. The biological activities of IFNs are mostly dependent upon protein synthesis with selective subsets of proteins mediating individual activities. IFNs can also stimulate indirect antiviral and antitumor mechanisms, depending upon cellular differentiation and the induction of cytotoxic activity. |
25 | omplxafd | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID-19 patients: A meta-regression and decision tree analysis BACKGROUND: Coronavirus disease-2019 (COVID-19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID-19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by receiver operating characteristic curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in patients with COVID-19. RESULTS: A meta-analysis of 17 794 patients showed patients with high cardiac troponin I (OR = 5.22, 95% CI = 3.73-7.31, P < .001) and aspartate aminotransferase (AST) levels (OR = 3.64, 95% CI = 2.84-4.66, P < .001) were more likely to develop adverse outcomes. High troponin I more than 13.75 ng/L combined with either advanced age more than 60 years or elevated AST level more than 27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID-19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. |
6 | jat60k8t | what types of rapid testing for Covid-19 have been developed? | Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020 A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations. |
27 | 10v7kfcd | what is known about those infected with Covid-19 but are asymptomatic? | Comparison of Clinical Characteristics of Patients with Asymptomatic vs Symptomatic Coronavirus Disease 2019 in Wuhan, China This case series examines clinical characteristics of patients with asymptomatic vs symptomatic coronavirus disease 2019 in Wuhan, China. |
8 | 29izbpf8 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | On Identifying and Mitigating Bias in the Estimation of the COVID-19 Case Fatality Rate The relative case fatality rates (CFRs) between groups and countries are key measures of relative risk that guide policy decisions regarding scarce medical resource allocation during the ongoing COVID-19 pandemic. In the middle of an active outbreak when surveillance data is the primary source of information, estimating these quantities involves compensating for competing biases in time series of deaths, cases, and recoveries. These include time- and severity- dependent reporting of cases as well as time lags in observed patient outcomes. In the context of COVID-19 CFR estimation, we survey such biases and their potential significance. Further, we analyze theoretically the effect of certain biases, like preferential reporting of fatal cases, on naive estimators of CFR. We provide a partially corrected estimator of these naive estimates that accounts for time lag and imperfect reporting of deaths and recoveries. We show that collection of randomized data by testing the contacts of infectious individuals regardless of the presence of symptoms would mitigate bias by limiting the covariance between diagnosis and death. Our analysis is supplemented by theoretical and numerical results and a simple and fast open-source codebase at https://github.com/aangelopoulos/cfr-covid-19 . |
18 | i1w2snyy | what are the best masks for preventing infection by Covid-19? | The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks |
33 | guciupc8 | What vaccine candidates are being tested for Covid-19? | Vaccines Through Centuries: Major Cornerstones of Global Health Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the "Germ Theory of disease" of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, "The Decade of vaccines" was launched, and on April 1st 2012, the United Nations launched the "shot@Life" campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history. |
12 | pzjxsh02 | what are best practices in hospitals and at home in maintaining quarantine? | Collaborative Multi-Disciplinary Incident Command at Seattle Children's Hospital for Rapid Preparatory Pediatric Surgery Countermeasures to the COVID-19 Pandemic Abstract Washington State was the first U.S. state to have a patient test positive for COVID-19. Prior to this, our children's hospital proactively implemented an incident command structure which allowed for collaborative creation of safety measures, policies and procedures for both patients, families, staff and providers. Although the treatment and protective standards are continuously evolving, this commentary shares our thoughts on how an institution, specifically surgical services may develop collaborative process improvement to accommodate for rapid and ongoing change. Specific changes outlined include [1] early establishment of incident command [2] personal protective equipment conservation, [3] workforce safety, [4] surgical and ambulatory patient triage, and [5] optimization of trainee education. Please note that the contents of this manuscript are shared in the interest of providing collaborative information and are under continuous development as our regional situation changes. We recognize the limitations of this commentary and do not suggest that our approaches represent validated best practices. |
21 | 2apo9imk | what are the mortality rates overall and in specific populations | The confounded crude case-fatality rates for COVID-19 hide more than they reveal - a comparison of age-specific and age-adjusted rates between six countries Background The reported crude case-fatality rates (CFRs) vary widely between countries. The serious limitations of using crude rates for comparisons are sometimes overlooked. In this paper we examined to what extent the age distribution of the cases is responsible for the differences in CFRs between countries. Methods Data on COVID-19 were extracted from the reports of individual countries. Overall and age-specific CFRs were available for six countries. The CFRs by country were adjusted for age using the direct method, using the combined age-specific number of cases of all six countries as the standard population. Findings The age distribution of the cases varied widely between countries. The crude CFRs varied between 1.6% and 11%. The differences in the age-specific CFRs were much smaller and the age-adjusted rates were much closer than the crude rates. The ratio of the crude CFR for the country with the highest to that with the lowest, was reduced substantially from 7.4 to 2.3 for the age-adjusted rates. Conclusions The age structure of the cases dramatically impacts on the differences in the crude CFRs between countries. Adjusting for age substantially reduces this variation. Other factors such as the differences in the definition of the denominators, the definition of a case and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. Comparisons should be based on age-specific and age-adjusted rates. Key words: COVID-19, case-fatality rates, age-specific rates, age-adjusted rates, confounding |
13 | z6krvfee | what are the transmission routes of coronavirus? | An investigation of the combined effect of an annual mass gathering event and seasonal infectiousness on disease outbreak Abstract In this paper, we investigate the effects of recurring mass gathering event on the spread of an epidemic. Mass gatherings take place when a large number of people from different locations visit a particular region during a short time period. Such activity plays a crucial role in the epidemic spread as traveling facilitates the spread of an epidemic between disparate locations and crowded conditions can accelerate the disease transmission. An additional component that affects disease spread is the seasonality in transmission. In this paper, we study the interplay between the periodic natures of seasonal transmission and of an annual mass gathering event. We find that the timing of the gathering relative to the peak in transmissibility can have a profound impact on the likelihood of an outbreak. |
40 | 0c7tf0np | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Coronavirus hemagglutinin-esterase and spike proteins co-evolve for functional balance and optimal virion avidity Human coronaviruses OC43 and HKU1 are respiratory pathogen of zoonotic origin that have gained worldwide distribution. OC43 apparently emerged from a bovine coronavirus (BCoV) spill-over. All three viruses attach to 9-O-acetylated sialoglycans via spike protein S with hemagglutinin-esterase HE acting as a receptor-destroying enzyme. In BCoV, an HE lectin domain promotes esterase activity towards clustered substrates. OC43 and HKU1, however, lost HE lectin function as an adaptation to humans. Replaying OC43 evolution, we knocked-out BCoV HE lectin function and performed forced evolution-population dynamics analysis. Loss of HE receptor-binding selected for second-site mutations in S, decreasing S binding affinity by orders of magnitude. Irreversible HE mutations selected for cooperativity in virus swarms with low-affinity S minority variants sustaining propagation of high-affinity majority phenotypes. Salvageable HE mutations induced successive second-site substitutions in both S and HE. Apparently, S and HE are functionally interdependent and co-evolve to optimize the balance between attachment and release. This mechanism of glycan-based receptor usage, entailing a concerted, fine-tuned activity of two envelope protein species, is unique among CoVs, but reminiscent of that of influenza A viruses (IAVs). Apparently, general principles fundamental to virion-sialoglycan interactions prompted convergent evolution of two important groups of human and animal pathogens. |
46 | pdvqdgsw | what evidence is there for dexamethasone as a treatment for COVID-19? | Chloroquine and hydroxychloroquine in the management of COVID-19: much kerfuffle but little evidence Summary Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring. |
1 | uwj62cuv | what is the origin of COVID-19 | 2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China Abstract We reported two cases with community-acquired pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who returned from Wuhan, China in January, 2020. The reported cases highlight non-specific clinical presentations of 2019 novel coronavirus disease (COVID-19) as well as the importance of rapid laboratory-based diagnosis. |
1 | i6pv90s9 | what is the origin of COVID-19 | An evidence-based framework for priority clinical research questions for COVID-19 BACKGROUND: On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75 000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14 000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. METHODS: Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. RESULTS: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. CONCLUSIONS: Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Data based on internationally standardised protocols will inform clinical practice real-time. |
35 | vznb3puk | What new public datasets are available related to COVID-19? | Enhanced COVID-19 data for improved prediction of survival The current COVID-19 pandemic, caused by the rapid world-wide spread of the SARS-CoV-2 virus, is having severe consequences for human health and the world economy. The virus effects individuals quite differently, with many infected patients showing only mild symptoms, and others showing critical illness. To lessen the impact of the pandemic, one important question is which factors predict the death of a patient? Here, we construct an enhanced COVID-19 dataset by processing two existing databases (from Kaggle and WHO) and using natural language processing methods to enhance the data by adding local weather conditions and research sentiment. Author summary In this study, we contribute an enhanced COVID-19 dataset, which contains 183 samples and 43 features. Application of Extreme Gradient Boosting (XGBoost) on the enhanced dataset achieves 95% accuracy in predicting patients survival, with country-wise research sentiment, and then age and local weather, showing the most importance. All data and source code are available at http://ab.inf.uni-tuebingen.de/publications/papers/COVID-19. |
11 | 6rqd3fmj | what are the guidelines for triaging patients infected with coronavirus? | Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know The outbreak of the current 2019 novel coronavirus (2019-nCoV, now named SARS-CoV-2) infection has become a worldwide health threat. Currently, more information is needed so as to further understand the transmission and clinical characteristics of 2019-nCoV infection and the infection control procedures required. Recently, the role of the eye in transmitting 2019-nCoV has been intensively discussed. Previous investigations of other highly infectious human CoVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide useful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, and mechanisms of human CoV infection, and recommendations for infection control procedures. The role of the eye in the transmission of 2019-nCoV is discussed in detail. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct and share the same entry receptors for some respiratory viruses, the eye is rarely involved in human CoV infection, conjunctivitis is quite rare in patients with 2019-nCoV infection, and the CoV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with 2019-nCoV and SARS-CoV infection is also extremely low. This suggests that the eye is neither a preferred organ of human CoV infection nor a preferred gateway of entry for human CoVs for infecting the respiratory tract. However, pathogens that the ocular surface is exposed to might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through the lacrimal duct system and then cause respiratory tract infection. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs by droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice. |
23 | io8hm94a | what kinds of complications related to COVID-19 are associated with hypertension? | Familial hypercholesterolemia and COVID-19: triggering of increased sustained cardiovascular risk. Early data from Wuhan, China show that patients with COVID-19 are typically male, aged 40 to 60 years, and about one-third have comorbidities. Moreover, of 138 COVID-19 patients hospitalized in Wuhan and treated in an intensive care unit (ICU), 25% had cardiovascular disease and 58% hypertension; the respective figures for non-ICU-treated COVID-19 patients were 10% and 22% [1]. Based on these early data, a predisposition to acute cardiac complications related to underlying atherosclerotic cardiovascular disease (ASCVD) may significantly increase the severity of COVID-19 in susceptible individuals. |
48 | g7onopr1 | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | Effective Teaching and Examination Strategies for Undergraduate Learning During COVID-19 School Restrictions On Friday, March 13, 2020, all school teaching in the Republic of Trinidad and Tobago, West Indies was suspended until further notice because of the novel coronavirus COVID-19 pandemic. This immediately jeopardized the completion of course content at the University of the West Indies, St. Augustine campus. This article presents effective teaching and examination strategies that can be utilized in teaching undergraduates during COVID-19 school restrictions. The introductory digital electronics course of the Department of Electrical and Computer Engineering at the University of the West Indies will be utilized to demonstrate the merits of these strategies. The research will focus on demonstrating that the teaching methodologies utilized avoided the student performance from degrading below what has been experienced in the past 5 academic years. Student feedback on the methodology utilized is also incorporated in this article to highlight key benefits gained by students. |
3 | 2o3dvi2d | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | COVID-19 and the immune system. A close interaction between the virus SARS-CoV-2 and the immune system of an individual results in a diverse clinical manifestation of the COVID-19 disease. While adaptive immune responses are essential for SARS-CoV-2 virus clearance, the innate immune cells, such as macrophages, may contribute, in some cases, to the disease progression. Macrophages have shown a significant production of IL-6 suggesting they may contribute to the excessive inflammation in COVID-19 disease. Macrophage Activation Syndrome may further explain the high serum levels of CRP, which are normally lacking in viral infections. In adaptive immune responses, it has been revealed that cytotoxic CD8+ T cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3. Since SARS-CoV-2 restrains antigen presentation by downregulating MHC class I and II molecules and, therefore, inhibits the T cell-mediated immune responses, humoral immune responses also play a substantial role. Specific IgA response appears to be stronger and more persistent than IgM response. Moreover, IgM and IgG antibodies show similar dynamics in COVID-19 disease. |
21 | kp2ewbn1 | what are the mortality rates overall and in specific populations | El SARS-CoV-2, una nueva zoonosis pandémica que amenaza al mundo On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (> 85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines. |
38 | 0phtilhi | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19 BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in nearly 1,000,000 laboratory-confirmed cases including over 50,000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently cause asymptomatic infections. However, the underlying mechanism that confers these viral characteristics on high transmissibility and asymptomatic infection remain incompletely understood. METHODS: We comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison. RESULTS: SARS-CoV-2 infected and replicated in human lung tissues more efficiently than that of SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20 folds more infectious virus particles than that of SARS-CoV from the infected lung tissues (P<0.024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes, and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative pro-inflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently. CONCLUSIONS: Our study provided the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provided important insights on the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2. |
29 | jcqhxzih | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | Risk of drug-induced Long QT Syndrome associated with the use of repurposed COVID-19 drugs: a systematic review Background: The World Health Organization first declared SARS-CoV-2 (COVID-19) a pandemic on March 11, 2020. There are currently no vaccines or therapeutic agents proven efficacious to treat COVID-19. So, whether existing approved drugs could be repurposed and used off-label for the treatment of novel COVID-19 disease is being explored. Methods: A thorough literature search was performed to gather information on the pharmacological properties and toxicity of 6 drugs (azithromycin, chloroquine, favipiravir, hydroxychloroquine, lopinavir/ritonavir, remdesivir) proposed to be repurposed to treat COVID-19. Researchers emphasized affinity of these drugs to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether-a-go-go gene (hERG), their propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Risk of drug-induced Long QT Syndrome (LQTS) for these drugs was quantified by comparing six indices used to assess such risk and by querying the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System database with specific key words. Data are also provided to compare the level of risk for drug-induced LQTS by these drugs to 23 other, well-recognized, torsadogenic compounds. Results: Estimators of LQTS risk levels indicated a very-high or high risk for all COVID-19 repurposed drugs except for azithromycin, although cases of TdP have been reported following the administration of this drug. There was an excellent agreement among the various indices used to assess risk of drug-induced LQTS for the six repurposed drugs and the 23 torsadogenic compounds. Conclusion: The risk-benefit assessment for the use of repurposed drugs to treat COVID-19 is complicated since benefits are currently anticipated, not proven. Mandatory monitoring of the QT interval shall be performed as such monitoring is possible for hospitalized patients or by the use of biodevices for outpatients initiated on these drugs. |
4 | yo3cp5vs | what causes death from Covid-19? | KAPITEL 13 Infektionskrankheiten Zur Orientierung Infektionskrankheiten werden durch Pathogene verursacht, die sich im Wirt vermehren: Ektoparasiten, Helminthen, Protozoen, Pilze, Bakterien, Viren, Prionen. Infektionskrankheiten können alle Organe bzw. Organsysteme befallen. Entstehung und Verlauf werden durch Faktoren beeinflusst, die sich grob einteilen lassen in Erreger- und Wirtsfaktoren. Die Kenntnis und richtige Einschätzung dieser Faktoren sind entscheidend für Diagnostik und Therapie dieser Erkrankungen. |
25 | m8x2ryx5 | which biomarkers predict the severe clinical course of 2019-nCOV infection? | The Association of Lymphocyte count and levels of CRP, D-Dimer, and LDH with severe coronavirus disease 2019 (COVID-19): A Meta-Analysis The rapid progression of Coronavirus disease 2019 (COVID-19) and its increasing burden on health systems necessitate the identification of parameters of severe infection to help in monitoring, prognoses and development of treatment algorithms. This review aims to investigate the association of lymphocyte count, CRP, LDH, and D-Dimer with the severe form of COVID-19. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, WHO-Virtual Health Library (VHL), and ScienceDirect were used for the systematic search. Random effects model was used to estimate the pooled standardized mean differences (SMD) with the corresponding 95% confidence interval (CI), using OpenMeta Analyst software. A total of 11 studies, with 2437 COVID-19 patients, which fulfilled the eligibility criteria were included in the meta-analysis. The analysis revealed that lymphocyte count was significantly lower in patients with the severe form of COVID-19 (SMD = - 1.025, P value <.001). Also, the analysis of SMD showed that patients with severe COVID-19 have a significantly higher serum levels of CRP (SMD = 3.363, P value <.001), D-Dimer (SMD = 1.073, P value <.001), and LDH (SMD = 3.345, P value <.001). Low lymphocyte count and high levels of CRP, LDH, and D-Dimer are associated with severe COVID-19. These laboratory markers could be used as clinical indicators of worsening illness and poor prognosis of COVID-19. |
4 | qyz28rqc | what causes death from Covid-19? | Intradural vertebral endarterectomy with nonautologous patch angioplasty for refractory vertebrobasilar ischemia: Case report and literature review. BACKGROUND The natural history of patients with symptomatic vertebrobasilar ischemic symptoms due to chronic bilateral vertebral artery occlusive disease is progressive, and poses significant challenges when refractory to medical therapy. Surgical treatment options depend largely on location and characteristics of the atheroma (s), and generally include percutaneous transluminal angioplasty (PTA) with or without stent placement, posterior circulation revascularization (bypass), extracranial vertebral artery reconstruction, or vertebral artery endarterectomy. CASE DESCRIPTION We present the case of a 56-year-old male with progressive vertebrobasilar ischemia due to tandem lesions in the right vertebral artery at the origin and intracranially in the V4 segment. The contralateral vertebral artery was occluded to the level of posterior inferior cerebellar artery (PICA) and posterior communicating arteries were absent. Following PTA and stent placement at the right vertebral artery origin, the patient was successfully treated with intradural vertebral artery endarterectomy (V4EA) and patch angioplasty via the far lateral approach. Distal endovascular intervention at the V4 segment proved not technically feasible after multiple attempts. CONCLUSIONS V4EA is an uncommonly performed procedure, but may be considered for carefully selected patients. The authors' techniques and indications are discussed. Historical outcomes, relevant anatomic considerations, and lessons learned are reviewed from the literature. |
17 | 20w0w53s | are there any clinical trials available for the coronavirus | Lopinavir/ritonavir use in Covid-19 infection: is it completely non-beneficial? Covid-19 infection caused by the novel coronavirus SARS-COV-2 continues to be a major global health challenge. Till date, no drug has been approved for the treatment of this infection. A number of medications have been proposed and there are ongoing clinical trials around the world to find a suitable treatment. A recent randomised control trial compared lopinavir/ritonavir with standard care among 199 patients with severe Covid-19 infection and concluded that there was no significant reduction in mortality rate with lopinavir/ritonavir. However, there are a few important lessons which may be learnt from the study apart from the statistical reduction in mortality rate. There was a numerical reduction in mortality rate, less intensive care unit stay and less complications in the lopinavir-ritonavir group. This article points out some of those important lessons with some suggestions for future clinical trials. |
3 | 7gqzyzjz | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | The case for Chronotherapy in COVID‐19 induced Acute Respiratory Distress Syndrome (ARDS). COVID‐19, the disease resulting from infection by a novel coronavirus: SARS‐Cov2 that has rapidly spread since November 2019 leading to a global pandemic. SARS‐Cov2 has infected over 4 million people and caused over 290,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of Acute Respiratory Distress Syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti‐inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS and thus chronotherapy may be used to effectively manage ARDS in COVID‐19 patients. |
29 | nxhazxja | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | Immunogenicity of SARS-CoV: the Receptor-Binding Domain of S Protein is a Major Target of Neutralizing Antibodies |
25 | x23ej29m | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study Summary Background In December, 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The number of affected pregnant women is increasing, but scarce information is available about the clinical features of COVID-19 in pregnancy. This study aimed to clarify the clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19. Methods In this retrospective, single-centre study, we included all pregnant women with COVID-19 who were admitted to Tongji Hospital in Wuhan, China. Clinical features, treatments, and maternal and fetal outcomes were assessed. Findings Seven patients, admitted to Tongji Hospital from Jan 1, to Feb 8, 2020, were included in our study. The mean age of the patients was 32 years (range 29–34 years) and the mean gestational age was 39 weeks plus 1 day (range 37 weeks to 41 weeks plus 2 days). Clinical manifestations were fever (six [86%] patients), cough (one [14%] patient), shortness of breath (one [14%] patient), and diarrhoea (one [14%] patient). All the patients had caesarean section within 3 days of clinical presentation with an average gestational age of 39 weeks plus 2 days. The final date of follow-up was Feb 12, 2020. The outcomes of the pregnant women and neonates were good. Three neonates were tested for SARS-CoV-2 and one neonate was infected with SARS-CoV-2 36 h after birth. Interpretation The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of non-pregnant adults with COVID-19 that have been reported in the literature. Funding National Natural Science Foundation of China, Hubei Provincial Natural Science Foundation of China. |
5 | gqno0hkq | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Is traditional Chinese medicine useful in the treatment of COVID-19? |
20 | zzgh49ck | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | NERVOUS SYSTEM VIRUSES |
36 | 03isjlif | What is the protein structure of the SARS-CoV-2 spike? | Drug repurposing using computational methods to identify therapeutic options for COVID-19 PURPOSE: Recently, the world has been dealing with a new type of coronavirus called COVID-19 that in terms of symptoms is similar to the SARS coronavirus. Unfortunately, researchers could not find a registered therapy to treat the infection related to the virus yet. Regarding the fact that drug repurposing is a good strategy for epidemic viral infection, we applied the drug repurposing strategy using virtual screening to identify therapeutic options for COVID-19. For this purpose, five proteins of COVID-19 (3-chymotrypsin-like protease (3CLpro), Papain-Like protease (PLpro), cleavage site, HR1 and RBD in Spike protein) were selected as target proteins for drug repositioning. METHODS: First, five proteins of COVID-19 were built by homology modeling. Then FDA-approved drugs (2471 drugs) were screened against cleavage site and RBD in Spike protein via virtual screening. One hundred and twenty-eight FDA-approved drugs with the most favorable free-binding energy were attached to the cleavage site and RBD in Spike protein. Of these 128 drugs, 18 drugs have either been used currently as antiviral or have been reported to possess antiviral effects. Virtual screening was then performed for the 18 selected drugs with ACE2, 3CLpro and PLpro and HR1 and TMPRSS2. RESULTS: According to the results, glecaprevir, paritaprevir, simeprevir, ledipasvir, glycyrrhizic acid, TMC-310911, and hesperidin showed highly favorably free binding energies with all tested target proteins. CONCLUSION: The above-mentioned drugs can be regarded as candidates to treat COVID-19 infections, but further study on the efficiency of these drugs is also necessary. |
17 | 7yq8zqxq | are there any clinical trials available for the coronavirus | SARS-CoV-2 Vaccines: Status Report SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population. |
11 | iech2khq | what are the guidelines for triaging patients infected with coronavirus? | Adult cardiac surgery during the COVID-19 Pandemic: A Tiered Patient Triage Guidance Statement Abstract In the setting of the current novel coronavirus pandemic, this document has been generated to provide guiding statements for the adult cardiac surgeon to consider in a rapidly evolving national landscape. Acknowledging the risk for a potentially prolonged need for cardiac surgery procedure deferral, the authors have created this proposed template for physicians and interdisciplinary teams to consider in protecting their patients, institution and their highly specialized cardiac surgery team. In addition, recommendations on the transition from traditional in-person patient assessments and outpatient follow-up are provided. Lastly, we advocate that the cardiac surgeon must continue to serve as leaders, experts, and relevant members of our medical community, shifting our role as necessary in this time of need. |
4 | b2yalnrx | what causes death from Covid-19? | A Model for the Testing and Tracing Needed to Suppress COVID-19 This paper presents a simple mathematical model that answers how much testing and tracing we need to do to suppress new surges of COVID-19 infections after reopening. We derived the model by modifying the SEIR model taking into the effects of testing and tracing. The following equation is one of the essential outcomes of the model: {rho}>(R0S/N-1)/(D(1+{eta}R0)) Where {rho} is the percentage of infectious people that have to be detected per day, R0 is the basic reproduction number, S/N is the percentage of the susceptible population over the entire population, D is the length of the infectious period, and {eta} is the percentage of close contacts that have to be traced. If the above equation is satisfied, we can bring the effective reproduction number Re to below 1 to get the transmission suppressed. This model demonstrates that together with social-distancing measures such as wearing masks in public, with a reasonable amount of testing and tracing, we may suppress the COVID-19 transmission for good. For example, if social distancing measures can bring R0 to below 1.2, for D being 10 days, in places where 15% people have developed antibodies, we can suppress the transmission by detecting only 0.13% of the infectious population daily while tracing 50% of their close contacts. The model provides intuitive insights and quantitative guidance for policymakers and public health practitioners to deploy the testing and tracing resources optimally. |
24 | i938t2wy | what kinds of complications related to COVID-19 are associated with diabetes | Podocyte ACE2 protects against diabetic nephropathy As new components of the renin–angiotensin system (RAS) are elucidated, our understanding of the complexities of their interactions also advances. Previous studies have determined that podocytes possess a local RAS that can generate angiotensin II. Podocytes have also been shown to express angiotensin-converting enzyme 2 (ACE2), which can decrease angiotensin II levels by generation of angiotensin-(1–7). Nadarajah et al. now show that increased podocyte ACE2 activity can attenuate the development of diabetic nephropathy. |
30 | 8y3t0r2d | is remdesivir an effective treatment for COVID-19 | Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2 BACKGROUND: The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China. METHODS: All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People's Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18–86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1–6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution. FINDINGS: The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3–4 days. CONCLUSION: SARS-CoV-2 infection can be confirmed based on the patient's history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia. |
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