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47 | jubwcobb | what are the health outcomes for children who contract COVID-19? | Efficacy and Safety of Antibiotic Agents in Children with COVID-19: A Rapid Review Background: The aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients. Methods: We searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis. Results: Six studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted odds ratio [OR] 0.84, 95% confidence interval [CI] 0.47-1.51, P = 0.56) and improvement in MERS-CoV RNA clearance (adjusted hazard ratio [HR] 0.88, 95% CI 0.47, -1.64], P = 0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid. Conclusions: The benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection. |
4 | fqs40ivc | what causes death from Covid-19? | Emergence of COVID-19 Infection: What Is Known and What Is to Be Expected-Narrative Review Article BACKGROUND: The discovery of the coronavirus disease 2019 (COVID-19) during a pneumonia outbreak in Wuhan city (China) has raised a global public health concern, as the city consists of around 11 million people and is considered a major transport and logistics hub. This deadly virus caused the world to be in high alert as the death toll and the number of confirmed cases is continuously rising since the first case was reported. The Chinese government warned that the transmission ability of the virus is increasing, and international efforts are needed to overcome this outbreak. The purpose of this review is to focus on the published articles about the new virus, which will give an insight into the current state of research and data available, as well as recommending future studies. METHODS: For this narrative review, more than 20 relevant scientific articles and reports were considered from various databases (e.g., Google Scholar, PubMed and Science Direct) using keywords such as Coronavirus Outbreak, COVID-19, Emerging Epidemics, Emerging Infections, and Novel Coronavirus. RESULTS: The results from this review show that the situation is rapidly evolving, as human-to-human transmission is occurring, and the number of new cases and mortalities is increasing by the day and on a global level. There is still ambiguity about mutation risks and how the virus spreads as the source was not yet identified. Major gaps in knowledge about the origin of the virus, epidemiology and transmission impose a great challenge, which emphasizes the need for further studies in the future. |
34 | 9p6lc8km | What are the longer-term complications of those who recover from COVID-19? | Rehab facilities face COVID-19 crunch as more patients recover. |
13 | baoqgu8v | what are the transmission routes of coronavirus? | Intrauterine vertical transmission of SARS‐CoV‐2: what we know so far |
10 | 3fflt6a3 | has social distancing had an impact on slowing the spread of COVID-19? | Building resilience against biological hazards and pandemics: COVID-19 and its implications for the Sendai Framework Abstract 2020 has become the year of coping with COVID-19. This year was to be the "super year" for sustainability, a year of strengthening global actions to accelerate the transformations required for achieving the 2030 agenda. We argue that 2020 can and must be a year of both. Thus we call for more utilisation of the health-emergency disaster risk management (Health-EDRM) framework to complement current responses to COVID-19 and the patent risk of similar phenomena in the future. To make our case, we examine current responses to COVID-19 and their implications for the SFDRR. We argue that current mechanisms and strategies for disaster resilience, as outlined in the SFDRR, can enhance responses to epidemics or global pandemics such as COVID-19. In this regard, we make several general and DRR-specific recommendations. These recommendations concern knowledge and science provision in understanding disaster and health-related emergency risks, the extension of disaster risk governance to manage both disaster risks and potential health-emergencies, particularly for humanitarian coordination aspects; and the strengthening of community-level preparedness and response. |
8 | k6y7f9d2 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Modelling the Effect of Area-deprivation on COVID-19 Incidences: A Study of Chennai Megacity, India Abstract Objectives Socioeconomic inequalities may affect COVID-19 incidence. The goal of the research was to explore the association between deprivation of socioeconomic status (SES) and spatial patterns of COVID-19 incidence in Chennai megacity for unfolding the disease epidemiology. Study design Ecological (or contextual) study for electoral wards (sub-cities) of Chennai megacity. Methods Using data of confirmed COVID-19 cases from May 15, 2020, to May 21, 2020, for 155 electoral wards obtained from the official website of the Chennai municipal corporation, we examined the incidence of COVID-19 diseases using two count regression models namely, Poisson Regression (PR) and Negative Binomial Regression (NBR). As explanatory factors, we considered area-deprivation that represented the deprivation of socioeconomic status (SES). An index of multiple deprivations (IMD) developed to measure the area-deprivation using an advanced local statistic, Geographically Weighted Principal Component Analysis (GWPCA). Based on the availability of appropriately scaled data, five domains (i.e. poor housing condition, low asset possession, poor availability of WaSH services, lack of household amenities and services, and gender disparity) were selected as components of the IMD in this study. Results The Hot-spot analysis revealed that area-deprivation was significantly associated with higher incidences of COVID-19 in Chennai megacity. The high variations (adj. R2: 72.2%) with the lower BIC (124.34) and AIC (112.12) for the NBR compared to PR suggests that the NBR model better explains the relationship between area-deprivation and COVID-19 incidences in Chennai megacity. NBR with two-sided tests, and p<0.05 was considered statistically significant. The outcome of the PR and NBR suggests that when all other variables were constant, according to NBR, the relative risk (RR) of COVID-19 incidences was 2.19 for the wards with high housing deprivation or in other words, the wards with high housing deprivation having 119% higher probability (RR= e0.786=2.19, 95% CI=1.98 to 2.40) compared to areas with low deprivation. Similarly, in the wards with poor availability of WaSH services, chances of having COVID-19 incidence was 90% higher compared to the wards with good WaSH services (RR= e0.642=1.90, 95% CI=1.79 to 2.00). Spatial risks of COVID-19 infections were predominantly concentrated in the wards with higher levels of area-deprivation which were mostly located in the north-eastern parts of Chennai megacity. Conclusions We formulated an area-based IMD, which was substantially related to COVID-19 incidences in the Chennai megacity. This study highlights that the risks of COVID-19 infections tend to be higher in more deprived areas of SES and the north-eastern part of Chennai megacity was predominantly high-risk areas. Our results can guide measures of COVID-19 control and prevention by considering spatial risks and area-deprivation. |
30 | uxyb4vih | is remdesivir an effective treatment for COVID-19 | A Library of Nucleotide Analogues Terminate RNA Synthesis Catalyzed by Polymerases of Coronaviruses that Cause SARS and COVID-19 SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 worldwide pandemic. We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine. We report here the evaluation of a library of nucleoside triphosphate analogues with a variety of structural and chemical features as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2. These features include modifications on the sugar (2' or 3' modifications, carbocyclic, acyclic, or dideoxynucleotides) or on the base. The goal is to identify nucleotide analogues that not only terminate RNA synthesis catalyzed by these coronavirus RdRps, but also have the potential to resist the viruses' exonuclease activity. We examined these nucleotide analogues for their ability to be incorporated by the RdRps in the polymerase reaction and to prevent further incorporation. While all 11 molecules tested displayed incorporation, 6 exhibited immediate termination of the polymerase reaction (triphosphates of Carbovir, Ganciclovir, Stavudine and Entecavir; 3'-OMe-UTP and Biotin-16-dUTP), 2 showed delayed termination (Cidofovir diphosphate and 2'-OMe-UTP), and 3 did not terminate the polymerase reaction (2'-F-dUTP, 2'-NH(2)-dUTP and Desthiobiotin-16-UTP). The coronaviruses possess an exonuclease that apparently requires a 2'-OH at the 3'-terminus of the growing RNA strand for proofreading. In this study, all nucleoside triphosphate analogues evaluated form Watson-Crick-like base pairs. The nucleotide analogues demonstrating termination either lack a 2'-OH, have a blocked 2'-OH, or show delayed termination. Thus, these nucleotide analogues are of interest for further investigation to evaluate whether they can evade the viral exonuclease activity. Prodrugs of five of these nucleotide analogues (Cidofovir, Abacavir, Valganciclovir/Ganciclovir, Stavudine and Entecavir) are FDA-approved medications for treatment of other viral infections, and their safety profiles are well established. After demonstrating potency in inhibiting viral replication in cell culture, candidate molecules can be rapidly evaluated as potential therapies for COVID-19. |
23 | f1ofvu29 | what kinds of complications related to COVID-19 are associated with hypertension? | Current status and progress of 2019 novel coronavirus pneumonia/ 中华危重病急救医学 Recently, the 2019 novel coronavirus (2019-nCoV) pneumonia outbroke in Wuhan and rapidly spread to all over China and even the world. Because of the strong infectivity and various clinical symptoms, it has brought certain difficulties to the epidemic prevention and control. Currently there is no specific drug for 2019-nCoV. Previous drugs used to treat other coronaviruses may be effective, but further clinical trials remain needed. We reviewed literature on the epidemiology, etiology, clinical manifestations, imaging manifestations, laboratory examination, diagnosis, complications, treatment and outcome of 2019-nCoV pneumonia. |
28 | l7rn00vq | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Abstracts from the 36th Annual Meeting of the Society of General Internal Medicine |
14 | vf2pw4ki | what evidence is there related to COVID-19 super spreaders | All together to Fight COVID-19 Novel coronavirus disease (COVID-19), named a pandemic by the WHO, is the current global health crisis. National and international collaboration are indispensable for combating COVID-19 and other similar potential outbreaks. International efforts to tackle this complex problem have led to remarkable scientific advances. Yet, as a global society, we can and must take additional measures to fight this pandemic. Undoubtedly, our approach toward COVID-19 was not perfect, and testing has not been deployed fast enough to arrest the epidemic early on. It is critical that we revise our approaches to be more prepared for pandemics as a united body by promoting global cooperation and commitment. |
4 | kpjp0sx4 | what causes death from Covid-19? | Acute respiratory failure in COVID-19: is it "typical" ARDS? In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China. The World Health Organization (WHO) declared this outbreak a significant threat to international health. COVID-19 is highly infectious and can lead to fatal comorbidities especially acute respiratory distress syndrome (ARDS). Thus, fully understanding the characteristics of COVID-19-related ARDS is conducive to early identification and precise treatment. We aimed to describe the characteristics of COVID-19-related ARDS and to elucidate the differences from ARDS caused by other factors. COVID-19 mainly affected the respiratory system with minor damage to other organs. Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation. The clinical manifestations were relatively mild in some COVID-19 patients, which was inconsistent with the severity of laboratory and imaging findings. The onset time of COVID-19-related ARDS was 8–12 days, which was inconsistent with ARDS Berlin criteria, which defined a 1-week onset limit. Some of these patients might have a relatively normal lung compliance. The severity was redefined into three stages according to its specificity: mild, mild-moderate, and moderate-severe. HFNO can be safe in COVID-19-related ARDS patients, even in some moderate-severe patients. The more likely cause of death is severe respiratory failure. Thus, the timing of invasive mechanical ventilation is very important. The effects of corticosteroids in COVID-19-related ARDS patients were uncertain. We hope to help improve the prognosis of severe cases and reduce the mortality. |
25 | uq0xan34 | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Biomarker discovery in infectious diseases using SELDI. Surface enhanced laser desorption ionization-time of flight is a mass spectrometric-based method that requires a minimal amount of sample for analysis and can be used for high-throughput screening. It has been used to discover serum or tissue protein signatures and biomarkers for infectious diseases in the fields of virology (hepatitis B and C viruses, severe acute respiratory syndrome, HIV-1, human T-cell leukemia virus-1 and BK virus), parasitology (trypanosomiasis) and bacteriology (intra-amniotic inflammation, tuberculosis and bacterial endocarditis). The protein signatures, or biomarkers, can be used to diagnose infection, predict disease states and to inform on disease processes. Careful attention to experimental design, sample handling and storage, and the use of appropriate internal controls is crucial to success. |
2 | 1cpoo3b5 | how does the coronavirus respond to changes in the weather | Seasonal Fluctuations of Astrovirus, But Not Coronavirus Shedding in Bats Inhabiting Human-Modified Tropical Forests Emerging infectious diseases (EIDs) are considered a major threat to global health. Most EIDs appear to result from increased contact between wildlife and humans, especially when humans encroach into formerly pristine habitats. Habitat deterioration may also negatively affect the physiology and health of wildlife species, which may eventually lead to a higher susceptibility to infectious agents and/or increased shedding of the pathogens causing EIDs. Bats are known to host viruses closely related to important EIDs. Here, we tested in a paleotropical forest with ongoing logging and fragmentation, whether habitat disturbance influences the occurrence of astro- and coronaviruses in eight bat species. In contrast to our hypothesis, anthropogenic habitat disturbance was not associated with corona- and astrovirus detection rates in fecal samples. However, we found that bats infected with either astro- or coronaviruses were likely to be coinfected with the respective other virus. Additionally, we identified two more risk factors influencing astrovirus shedding. First, the detection rate of astroviruses was higher at the beginning of the rainy compared to the dry season. Second, there was a trend that individuals with a poor body condition had a higher probability of shedding astroviruses in their feces. The identification of risk factors for increased viral shedding that may potentially result in increased interspecies transmission is important to prevent viral spillovers from bats to other animals, including humans. |
11 | ysbopqqq | what are the guidelines for triaging patients infected with coronavirus? | Clinical features and management of severe COVID-19: A retrospective study in Wuxi, Jiangsu Province, China Objective: We aimed to investigate clinical features and management of 55 COVID-19 patients in Wuxi, especially severe COVID-19. Methods: Epidemiological, demographic, clinical, laboratory, imaging, treatment, and outcome data of patients were collected. Follow-up lasted until April 6, 2020. Results: All 55 patients included 47 (85.5%) non-severe patients and 8 (14.5%) severe patients. Common comorbidities were hypertension and diabetes. Common symptoms were fever, cough and sputum. Lymphopenia was a common laboratory finding, and ground-glass opacity was a common chest CT feature. All patients received antiviral therapy of α-interferon inhalation and lopinavir-ritonavir tablets. Common complications included acute liver injury and respiratory failure. All patients were discharged. No death was occurred and no medical staff got infected. Patients with severe COVID-19 showed significantly older age, decreased lymphocytes, increased C reactive protein, and higher frequency of bilateral lung infiltration compared to non-severe patients. Significantly more treatments including antibiotic therapy and mechanical ventilation, longer hospitalization stay and higher cost were shown on severe patients. Conclusions: Our study suggested that patients with severe COVID-19 may be more likely to have an older age, present with lymphopenia and bilateral lung infiltration, receive multiple treatments and stay longer in hospital. |
13 | 2lp3fead | what are the transmission routes of coronavirus? | Technologies to Optimize the Care of Severe Coronavirus Disease 2019 Patients for Health Care Providers Challenged by Limited Resources Health care systems are belligerently responding to the new Coronavirus Disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a specific condition, whose distinctive features are severe hypoxemia associated with (>50% of cases) normal respiratory system compliance.(1) When a patient requires intubation and invasive ventilation, the outcome is poor,(2–4) and the length of stay in the intensive care unit (ICU) is usually 2or 3 weeks.(2) In this article, theauthors review several technological devices, which could support health care providers at the bedside to optimizethe care for COVID-19 patients who are sedated, paralyzed, and ventilated. Particular attention is provided to the use of videolaryngoscopes (VL) because these can assist anesthetists to perform a successful intubation outside the ICU while protecting health care providers from this viral infection. Authors will also review processed electroencephalographic (EEG) monitors which are used to better titrate sedation and the train-of-four monitors which are utilizedto better titrate neuromuscular blocking agents in the view of sparing limited pharmacological resources. COVID-19 can rapidly exhaust human and technological resources too within the ICU. This review features a series of technological advancements that can significantly improve the care of patients requiring isolation. The working conditions in isolation could cause gaps or barriers in communication, fatigue, and poor documentation of provided care. The available technology has several advantages including (a) facilitating appropriate paperless documentation and communication between all health care givers working in isolation rooms or large isolation areas; (b) testing patients and staff at the bedside using smart point-of-care diagnostics (SPOCD) to confirm COVID-19 infection; (c) allowing diagnostics and treatment at the bedside through point-of-care ultrasound (POCUS) and thromboelastography(TEG); (d) adapting the use of anesthetic machines and the use of volatile anesthetics. Implementing technologies for safeguarding health care providers as well as monitoring the limited pharmacological resources are paramount. Only by leveraging new technologies, it will be possible to sustain and support health care systems during the expected long course of this pandemic. |
47 | sb7v3m2w | what are the health outcomes for children who contract COVID-19? | The Mental Health Burden of the COVID-19 Pandemic on Physical Therapists We evaluated the mental health burden of coronavirus disease (COVID-19) on physical therapists, including their stress and anxiety levels, who were at risk of developing psychological distress and other mental health symptoms. A questionnaire survey was conducted with physical therapists of three university hospitals in South Korea on 10 April 2020. The questionnaires evaluated the presence of anxiety and depression in the respondents. Among the 65 physical therapists who completed our survey, 21 (32.3%) and 12 (18.5%) physical therapists reported having symptoms of anxiety and depression, respectively. If a physical therapist was living with a ≤6-year-old infant or child, the possibility of the presence of anxiety was significantly higher. The risk of depression among those who were in their 30 s and 50 s was significantly higher than among those in their 20 s. Thus, physical therapists living with a ≤6-year-old infant or child and those in their 30 s and 50 s need special attention. |
11 | s57y3ybu | what are the guidelines for triaging patients infected with coronavirus? | Extracorporeal Membrane Oxygenation – Crucial Considerations during the Coronavirus Crisis |
22 | mtg4l456 | are cardiac complications likely in patients with COVID-19? | The Heart in the Time of the 'Coronavirus' |
2 | 6nonzjbq | how does the coronavirus respond to changes in the weather | The higher temperature and ultraviolet, the lower COVID-19 prevalence – Meta-regression of data from large U.S. cities |
16 | x11dr866 | how long does coronavirus remain stable on surfaces? | Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection. |
34 | mnuibcfa | What are the longer-term complications of those who recover from COVID-19? | COVID-19 and telepsychiatry: an evidence-based guidance for clinicians. BACKGROUND COVID-19 presents unique challenges in healthcare, including mental health care provision. Telepsychiatry can provide an alternative to face to face assessment and can also be used creatively with other technologies to enhance care, but clinicians and patients may feel underconfident about embracing this new way of working. OBJECTIVE The aim was to produce an open access, easy-to-consult and reliable source of information and guidance about telepsychiatry and COVID-19 using an evidence-based approach. METHODS We systematically searched existing English language guidelines and websites for information on telepsychiatry in the context of COVID-19 up to and including May 2020. We used broad search criteria and included pre-COVID-19 guidelines and also other digital mental health topics where relevant. We summarised the data we extracted as answers to specific clinical questions. RESULTS Findings from this study are presented as both a short practical checklist for clinicians and a detailed table with a full summary of all the guidelines. The summary tables are also available on an open access webpage (https://oxfordhealthbrc.nihr.ac.uk/our-work/oxppl/table-5-digital-technologies-and-telepsychiatry/) which is regularly updated. These findings reflect the strong evidence base for the use of telepsychiatry and include guidelines for many of the common concerns expressed by clinicians about practical implementation, technology, information governance and safety. Guidelines across countries differ significantly, with UK guidelines more conservative and focussed on practical implementation, and US guidelines more expansive and detailed. Guidelines on possible combination with other digital technologies such as apps, for example from the FDA, NHS Apps Library and NICE are less detailed. Several key areas were not represented. Whilst some special populations such as child and adolescent, older adult and cultural issues are specifically included, important populations such as learning disabilities, psychosis, personality disorder and eating disorders, which may present particular challenges for telepsychiatry, are not. In addition, initial consultation and follow-up sessions are not clearly distinguished. Finally, a hybrid model of care (combining telepsychiatry with other technologies and in-person care) is not explicitly covered by the existing guidelines. CONCLUSIONS We produced a comprehensive synthesis of guidance answering a wide range of clinical questions in telepsychiatry. This meets the urgent need for practical information for both clinicians and health care organisations who are rapidly adapting to the pandemic and implementing remote consultation. It reflects variations across countries and can be used as a basis for organisational change in the short and longer term. Providing easily accessible guidance is a first step, but will need cultural change to implement, as clinicians start to view telepsychiatry not just as a replacement, but as a parallel and complimentary form of delivering therapy, with its own advantages and benefits as well as restrictions. A combination or hybrid approach can be the most successful approach in the new world of mental health post-COVID-19 and guidance will need to expand to encompass the use of telepsychiatry in conjunction with other in-person and digital technologies, and also its use across all psychiatric disorders, not just those who are the first to access and engage with remote treatment. CLINICALTRIAL |
22 | 0nyj1sbm | are cardiac complications likely in patients with COVID-19? | Cardiovascular Implications in Patients Infected with Covid-19 and the Importance of Social Isolation to Reduce Dissemination of the Disease. Respiratory symptoms, especially the development of severe acute respiratory distress syndrome, dominate the discussion and initial concerns of the population and health professionals. However, the cardiovascular system is greatly affected by these conditions and is often responsible for complications and mortality of these patients. In order to show the cardiovascular implications in patients infected with COVID-19 and the importance of social isolation as an alternative to curb the spread of the disease, a literature review was carried out based on 37 articles, in English, Portuguese and Spanish, available on Scielo and PubMed. The findings showed that cardiac complications associated with COVID-19 infection are similar to those produced by: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. However, COVID-19 has a much greater and faster contamination and, unlike influenza, there is no vaccine or treatment available yet. In view of this, social isolation becomes a tool that can reduce and flatten the curve of cases and thus protect the people at higher risk, decreasing the chances of serious conditions related to the disease, potential deaths and the collapse of the country's health system. |
11 | 9whkfq2g | what are the guidelines for triaging patients infected with coronavirus? | Goals of Care in a Pandemic: Our Experience and Recommendations We propose that the palliative care team response will occur in two ways: first, communication and second, symptom management. Our experience with discussing goals of care with the family of a COVID-positive patient highlighted some expected and unexpected challenges. We describe these challenges along with recommendations for approaching these conversations. We also propose a framework for proactively mobilizing the palliative care workforce to aggressively address goals of care in all patients, with the aim of reducing the need for rationing of resources. |
33 | um3fa49r | What vaccine candidates are being tested for Covid-19? | Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development BACKGROUND: Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection. METHODS: We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines. FINDINGS: Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vaccines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization. INTERPRETATION: MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases. |
19 | t3zampk7 | what type of hand sanitizer is needed to destroy Covid-19? | PepMapper: A Collaborative Web Tool for Mapping Epitopes from Affinity-Selected Peptides Epitope mapping from affinity-selected peptides has become popular in epitope prediction, and correspondingly many Web-based tools have been developed in recent years. However, the performance of these tools varies in different circumstances. To address this problem, we employed an ensemble approach to incorporate two popular Web tools, MimoPro and Pep-3D-Search, together for taking advantages offered by both methods so as to give users more options for their specific purposes of epitope-peptide mapping. The combined operation of Union finds as many associated peptides as possible from both methods, which increases sensitivity in finding potential epitopic regions on a given antigen surface. The combined operation of Intersection achieves to some extent the mutual verification by the two methods and hence increases the likelihood of locating the genuine epitopic region on a given antigen in relation to the interacting peptides. The Consistency between Intersection and Union is an indirect sufficient condition to assess the likelihood of successful peptide-epitope mapping. On average from 27 tests, the combined operations of PepMapper outperformed either MimoPro or Pep-3D-Search alone. Therefore, PepMapper is another multipurpose mapping tool for epitope prediction from affinity-selected peptides. The Web server can be freely accessed at: http://informatics.nenu.edu.cn/PepMapper/ |
33 | 3qnva664 | What vaccine candidates are being tested for Covid-19? | Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels MERS-CoV seronegative and seropositive camels received a single intramuscular dose of ChAdOx1 MERS, a replication-deficient adenoviral vectored vaccine expressing MERS-CoV spike protein, with further groups receiving control vaccinations. Infectious camels with active naturally acquired MERS-CoV infection, were co-housed with the vaccinated camels at a ratio of 1:2 (infected:vaccinated); nasal discharge and virus titres were monitored for 14 days. Overall, the vaccination reduced virus shedding and nasal discharge (p = 0.0059 and p = 0.0274, respectively). Antibody responses in seropositive camels were enhancedby the vaccine; these camels had a higher average age than seronegative. Older seronegative camels responded more strongly to vaccination than younger animals; and neutralising antibodies were detected in nasal swabs. Further work is required to optimise vaccine regimens for younger seronegative camels. |
13 | yrq58n4k | what are the transmission routes of coronavirus? | PREDICTING THE EVOLUTION OF COVID-19 IN PORTUGAL USING AN ADAPTED SIR MODEL PREVIOUSLY USED IN SOUTH KOREA FOR THE MERS OUTBREAK Since original reports in Wuhan, China, the new coronavirus covid-19 has spread very quickly worldwide, leading the World Health Organization (WHO) to declare a state of pandemic. Moreover, as of the 13th of March 2020, the WHO has announced that the European continent is now the main centre of the pandemic. Many European governments have already implemented harsh measures to attempt to contain the spread of the virus. In Portugal, there are, as of the 20th of March 2020, 1020 confirmed cases. One of the questions many policy makers, and governments are asking themselves is how the spread is going to evolve in time. A timely idea of the amount of cases that will exist in a near future can allow governments and policy makers to act accordingly. In this study, I applied an adapted SIR model previously used in South Korea to model the MERS outbreak, which is also caused by a coronavirus, to estimate the evolution of the curve of active cases in the case of the Portuguese situation. As some of the parameters were unknown, and the data for Portugal is still scarce, given that the outbreak started later (first case on the 2nd of March) I used Italian data (first reported case in Italy on the 31st of January) to predict them. I then construct two or three different scenarios for the evolution of covid-19 in Portugal, considering both the effectiveness of the mitigation measurements implemented by the government, and the self-protective measures taken by the population, as explained in the South Korean model. In the out of control scenario, the number of active cases could reach as much as ~40,000 people by the beginning of April. If measures are appropriately taken this number can be reduced to about 800 cases. In case that some measures are taken, but their implementation is not done appropriately, the active cases could reach circa 7,000 people. The actual figures probably lie between the interval (~800-7,000) and the peak will be reached between 9th and the 20nd of April 2020. Without control and self-protective measures, this model predicts that the figures of active cases of SARS-covid-2 would reach a staggering ~40,000 people It shows the importance of control and self-protecting measure to bring down the number of affected people by following the recommendations of the WHO and health authorities. With the appropriate measures, this number can be brought down to ~800-7,000 people. Hopefully that will be the case not just in Portugal, but in the rest of the World. |
31 | wa6k2kv6 | How does the coronavirus differ from seasonal flu? | Etiology and Clinical Characteristics of Influenza-Like Illness (ILI) in Outpatients in Beijing, June 2010 to May 2011 BACKGROUND: Since May 2009, exposure of the population of Beijing, China to pH1N1 has resulted in an increase in respiratory illnesses. Limited information is available on the etiology and clinical characteristics of the influenza-like illness (ILI) that ensued in adults following the pH1N1 pandemic. METHODS: Clinical and epidemiological data of ILI in adults was collected. A total of 279 throat swabs were tested for twelve respiratory viruses using multiplex RT-PCR. Clinical characteristics of influenza A in outpatients versus test-negative patients were compared using Pearson's χ2 and the Mann-Whitney U test. 190 swabs were tested for pH1N1 by virus isolation. Consultation rates for ILI were compared between 2009 and 2010. RESULTS: One or two virus were detected in 29% of the samples. Influenza A virus (FLU-A) accounted for 22.9% (64/279). Other viruses were present at a frequency less than 3.0%. Cough was significantly associated with Influenza A virus infection (χ2, p<0.001). The positive rate of FLU-A was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to 2009. During the 2010–2011 influenza season, the incidence peaked in January 2011 in Beijing and north China. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks, although FLU-A remained the predominant virus for 2010 in Beijing. Symptomatically, cough was associated with FLU-A infection. The positive rate of influenza virus was consistent with changes in the ILI rate during the same period and there was a significant reduction in the incidence of ILI in 2010 when compared to that of 2009. |
19 | 75cotmn2 | what type of hand sanitizer is needed to destroy Covid-19? | Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients Abstract The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly and means a special risk for both immunosuppressed and comorbid patients. Knowledge about this growing infection is also increasing although many uncertainties remain, especially in the kidney transplant population. This manuscript presents a proposal for action with general and specific recommendations to protect and prevent infection in this vulnerable population such as kidney transplant recipients. |
8 | 2rc8n3x6 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | How lethal is the novel coronavirus, and how many undetected cases there are? The importance of being tested. There is big concern for estimating the lethality and the extent of undetected infections associated with the novel coronavirus SARS-CoV2 outbreak. While detailed epidemiological models are certainly needed, I suggest here an orthogonal approach based on a minimum number of parameters robustly fitted from the cumulative data easily accessible for all countries at the John Hopkins University database that became the worldwide reference for the pandemics. I show that, after few days from the beginning of the outbreak, the apparent death rate can be extrapolated to infinite time through regularized regression such as rescaled ridge regression. The variation from country to country of these extrapolated death rates appears to depend almost only (r^2=0.91) on the ratio between performed tests and detected cases even when the instantaneous apparent lethality rates are as different as 9% in Italy and 0.4% in Germany. Extrapolating to the limit of infinite number of tests, I obtain a death rate of 0.012+/- 0.012, in agreement with other estimates. The inverse relationship between the extrapolated death rate and the intensity tests allows estimating that more than 50% of cases were undetected in most countries, with more than 90% undetected cases in countries severely hit by the epidemics such as Italy. Finally, I propose to adopt the ratio between the cumulative number of recovered and deceased persons as an indicator that can anticipate the halting of the epidemics. |
26 | 41ogljo8 | what are the initial symptoms of Covid-19? | The establishment of reference sequence for SARS‐CoV‐2 and variation analysis Starting around December 2019, an epidemic of pneumonia, which was named COVID‐19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full‐length genomic sequences of SARAS‐CoV‐2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS‐CoV‐2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%‐100%) at the nucleotide level and 99.99% (99.79%‐100%) at the amino acid level. Although overall variation in open‐reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS‐COV‐2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS‐CoV‐2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS‐CoV‐2 infection in the future. |
6 | egjdy7o0 | what types of rapid testing for Covid-19 have been developed? | Rates of coinfection with other respiratory pathogens in patients positive for coronavirus disease 2019 (COVID‐19) OBJECTIVES: The purpose of this study was to assess coinfection rates of coronavirus disease 2019 (COVID‐19) with other respiratory infections on presentation. METHODS: This is a retrospective analysis of data from a 2 hospital academic medical centers and 2 urgent care centers during the initial 2 weeks of testing for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) , March 10, 2020 to March 23, 2020. Testing was targeted toward high‐risk patients following US Centers for Disease Control and Prevention guidelines. Demographics include age group and sex. Laboratory test results included SARS‐CoV‐2, rapid influenza A/B, and upper respiratory pathogen nucleic acid detection. Patient demographics and coinfections are presented overall and by test results with descriptive statistics. RESULTS: Complete laboratory results from the first 2 weeks of testing were available for 471 emergency department patients and 117 urgent care center patients who were tested for SARS‐CoV. A total of 51 (8.7%) patients tested positive for COVID‐19 with only 1 of these patients also testing positive for another respiratory infection. One of the patients positive for COVID‐19 also tested positive for influenza A. Among the 537 patients who were screened and tested negative for COVID‐19, there were 33 (6.1%) patients who tested positive in the upper respiratory pathogen nucleic acid detection test. CONCLUSION: In our study investigating coinfections among 51 patients testing positive for COVID‐19, 1 patient also tested positive for influenza A. Although we found limited coinfections in our emergency department and urgent care center patient populations, further research is needed to assess potential coinfection in patients with COVID‐19. |
15 | 3vwi5myc | how long can the coronavirus live outside the body | Perioperative Management of Patients Infected with the Novel Coronavirus: Recommendation from the Joint Task Force of the Chinese Society of Anesthesiology and the Chinese Association of Anesthesiologists The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients' airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients' needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions. |
39 | b2aik19c | What is the mechanism of cytokine storm syndrome on the COVID-19? | Silencing of immune activation with methotrexate in patients with COVID-19 |
27 | ylr2b8ck | what is known about those infected with Covid-19 but are asymptomatic? | COVID-19 and intracerebral haemorrhage: causative or coincidental? Pneumonia appears to be the most common manifestation of coronavirus disease 2019 (COVID-19), but some extrapulmonary involvement, such as gastrointestinal, cardiac and renal, has been reported. The limited clinical data about the virus's behavior to date, especially extrapulmonary symptoms, suggest that we should be aware of the possibility of initial cerebrovascular manifestations of COVID-19. |
35 | evc37gi0 | What new public datasets are available related to COVID-19? | Advances in disease diagnosis, vaccine development and other emerging methods to control pathogens in aquaculture Disease is still regarded as a major constraint to aquaculture production globally. Rapid disease diagnosis and vaccination play a huge part in the control of bacterial diseases, and there has been significant progress in both of these areas. This chapter considers the limitations of existing methods and reviews recent advances made in pathogen detection technologies and vaccine development methodologies. Future directions are discussed, including nanotechnology and reversed vaccinology. |
23 | tmrcgdal | what kinds of complications related to COVID-19 are associated with hypertension? | The importance of hypertension as a risk factor for severe illness and mortality in COVID-19 |
26 | slapc5xt | what are the initial symptoms of Covid-19? | A Chinese Case of Coronavirus Disease 2019 (COVID-19) Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey Controversy remains over whether the coronavirus disease 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period. |
39 | 1w7g6dkq | What is the mechanism of cytokine storm syndrome on the COVID-19? | Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19 As a zoonotic disease that has already spread globally to several million human beings and possibly to domestic and wild animals, eradication of coronavirus disease 2019 (COVID-19) appears practically impossible. There is a pressing need to improve our understanding of the immunology of this disease to contain the pandemic by developing vaccines and medicines for the prevention and treatment of patients. In this review, we aim to improve our understanding on the immune response and immunopathological changes in patients linked to deteriorating clinical conditions such as cytokine storm, acute respiratory distress syndrome, autopsy findings and changes in acute-phase reactants, and serum biochemistry in COVID-19. Similar to many other viral infections, asymptomatic disease is present in a significant but currently unknown fraction of the affected individuals. In the majority of the patients, a 1-week, self-limiting viral respiratory disease typically occurs, which ends with the development of neutralizing antiviral T cell and antibody immunity. The IgM-, IgA-, and IgG-type virus-specific antibodies levels are important measurements to predict population immunity against this disease and whether cross-reactivity with other coronaviruses is taking place. High viral load during the first infection and repeated exposure to virus especially in healthcare workers can be an important factor for severity of disease. It should be noted that many aspects of severe patients are unique to COVID-19 and are rarely observed in other respiratory viral infections, such as severe lymphopenia and eosinopenia, extensive pneumonia and lung tissue damage, a cytokine storm leading to acute respiratory distress syndrome, and multiorgan failure. Lymphopenia causes a defect in antiviral and immune regulatory immunity. At the same time, a cytokine storm starts with extensive activation of cytokine-secreting cells with innate and adaptive immune mechanisms both of which contribute to a poor prognosis. Elevated levels of acute-phase reactants and lymphopenia are early predictors of high disease severity. Prevention of development to severe disease, cytokine storm, acute respiratory distress syndrome, and novel approaches to prevent their development will be main routes for future research areas. As we learn to live amidst the virus, understanding the immunology of the disease can assist in containing the pandemic and in developing vaccines and medicines to prevent and treat individual patients. |
12 | o045bvn7 | what are best practices in hospitals and at home in maintaining quarantine? | CovProfile: profiling the viral genome and gene expressions of SARS-COV-2 The SARS-CoV-2 virus has infected more than one million people worldwide to date. Knowing its genome and gene expressions is essential to understand the virus' mechanism. Here, we propose a computational tool CovProfile to detect the viral genomic variations as well as viral gene expressions from the sequences obtained from Nanopore devices. We applied CovProfile to 11 samples, each from a terminally ill patient, and discovered that all the patients are infected by multiple viral strains, which might affect the reliability of phylogenetic analysis. Moreover, the expression of viral genes ORF1ab gene, S gene, M gene, and N gene are high among most of the samples. While performing the tests, we noticed a consistent abundance of transcript segments of MUC5B, presumably from the host, across all the samples. |
2 | og3myz22 | how does the coronavirus respond to changes in the weather | The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care Summary The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging 'return to normal' following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed. |
31 | h29uwe1d | How does the coronavirus differ from seasonal flu? | Avian influenza aided readiness for swine flu Despite gains from threat of bird flu, pandemic preparedness is patchy. |
15 | 431buxxr | how long can the coronavirus live outside the body | Understanding novel COVID-19: its impact on organ failure and risk assessment for diabetic and cancer patients Abstract The current pandemic outbreak of COVID-19 originated from Wuhan, China. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with significant mortality and morbidity rate. The severe risk factors are commonly detected in patients of older age and with medical comorbidities like cancer and diabetes. Scientists and doctors have scrambled to gain knowledge about the novel virus and its pathophysiology in order to discover possible therapeutic regimens and vaccines for COVID-19. The therapeutic strategies like targeting the viral genome emphasize the promising approach to target COVID-19. Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen. In this review article, we have presented the effect of SARS-CoV-2 infection in comorbid patients and discussed organ failure caused by this virus. Based on the data available from the scientific literature and ongoing clinical trials, we have focused on therapeutic strategies. We hope that we would fill the gaps that puzzled the researchers and clinicians with the best of our knowledge collected for the betterment of the patients for the coming future. |
49 | ipw96f03 | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection. SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs. |
4 | tls4p43h | what causes death from Covid-19? | Domestic Pig Unlikely Reservoir for MERS-CoV We tested the suitability of the domestic pig as a model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Inoculation did not cause disease, but a low level of virus replication, shedding, and seroconversion were observed. Pigs do not recapitulate human MERS-CoV and are unlikely to constitute a reservoir in nature. |
23 | j6wdshto | what kinds of complications related to COVID-19 are associated with hypertension? | COVID-19 in patients with cardiovascular diseases |
15 | nc8ktxeo | how long can the coronavirus live outside the body | Understanding Viral Transmission Behavior via Protein Intrinsic Disorder Prediction: Coronaviruses Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization enables quick identification of viruses with similar behaviors in transmission, regardless of genetic proximity. Based on this analysis, an empirical model for predicting the viral transmission behavior is developed. This model is able to explain some behavioral aspects of important coronaviruses that previously were not fully understood. The new predictor can be a useful tool for better epidemiological, clinical, and structural understanding of behavior of both newly emerging viruses and viruses that have been known for a long time. A potentially new vaccine strategy could involve searches for viral strains that are characterized by the evolutionary misfit between the peculiarities of the disorder distribution in their shells and their behavior. |
20 | edu1zuzt | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage with Human Liver Organoids The newly emerged pandemic coronavirus, SARS-CoV-2, has posed a significant public health threat worldwide. However, the mode of virus transmission and tissue tropism is not well established yet. Recent findings of substantial liver damage in patients and ACE2+ cholangiocytes in healthy liver tissues prompted us to hypothesize that human liver ductal organoids could serve as a model to determine the susceptibility and mechanisms underlining the liver damage upon SARS-CoV-2 infection. By single-cell RNA sequencing, we found that long-term liver ductal organoid culture preserved the human specific ACE2+ population of cholangiocytes. Moreover, human liver ductal organoids were permissive to SARS-CoV-2 infection and support robust replication. Notably, virus infection impaired the barrier and bile acid transporting functions of cholangiocytes through dysregulation of genes involved in tight junction formation and bile acid transportation, which could explain the bile acid accumulation and consequent liver damage in patients. These results indicate that control of liver damage caused directly by viral infection should be valued in treating COVID-19 patients. Our findings also provide an application of human organoids in investigating the tropism and pathogenesis of SARS-CoV-2, which would facilitate novel drug discovery. |
11 | 0agldesf | what are the guidelines for triaging patients infected with coronavirus? | A Machine Learning Model Reveals Older Age and Delayed Hospitalization as Predictors of Mortality in Patients with COVID-19 Objective: The recent pandemic of novel coronavirus disease 2019 (COVID-19) is increasingly causing severe acute respiratory syndrome (SARS) and significant mortality. We aim here to identify the risk factors associated with mortality of coronavirus infected persons using a supervised machine learning approach. Research Design and Methods: Clinical data of 1085 cases of COVID-19 from 13th January to 28th February, 2020 was obtained from Kaggle, an online community of Data scientists. 430 cases were selected for the final analysis. Random Forest classification algorithm was implemented on the dataset to identify the important predictors and their effects on mortality. Results: The Area under the ROC curve obtained during model validation on the test dataset was 0.97. Age was the most important variable in predicting mortality followed by the time gap between symptom onset and hospitalization. Conclusions: Patients aged beyond 62 years are at higher risk of fatality whereas hospitalization within 2 days of the onset of symptoms could reduce mortality in COVID-19 patients. |
45 | q4rfmyxo | How has the COVID-19 pandemic impacted mental health? | Uncovering psychobehavioral implications of SARS-CoV-2 infection in Iran. Iran is the country in Western Asia most impacted by the COVID-19 outbreak. A survey was conducted among the general public in Iran aimed at investigating psychobehavioural issues related to the COVID-19 outbreak, namely: 1) barriers to preventive measures against SARS-CoV-2 infection; 2) negative emotions toward SARS-CoV-2 infection; and 3) anxiety levels among the general public in Iran. A cross-sectional, web-based survey using an online questionnaire was carried out between 16 March and 1 April 2020. The six-item version of the State-Trait Anxiety Inventory (STAI-6) was used to assess anxiety levels. A total of 1,789 complete responses were received. Nearly 60% reported having difficulty in wearing a face mask to protect against SARS-CoV-2 infection. The mean and standard deviation (SD) for the total prevention barrier score was 35.8 (SD ± 7.1; range 18 to 68) out of a possible score of 72. Male respondents [odds ratio (OR) = 1.25; 95% confidence interval (CI) 1.03 to 1.51] and respondents who perceived their health status as poor/fair (OR = 1.49; 95% CI 1.31 to 1.82) were predictors of high prevention barriers. Negative emotions such as fear (74.6%), followed by depression (43.4%) and stigma (23.0%) associated with SARS-CoV-2 infection were reported. Respondents who perceived their health as poor/fair (OR = 2.19; 95% CI 1.57 to 3.04) reported a higher likelihood of having higher negative emotions. Findings on anxiety level revealed 68.0% (95% CI 65.8 to 70.1) reported moderate to severe anxiety. Respondents who perceived their health as poor/fair (OR = 3.46; 95% CI 12.22 to 5.40) and who were females (OR = 1.91; 95% CI 1.55 to 2.36) were predictors of moderate to severe anxiety. In conclusion, psychobehavioural interventions are needed to facilitate management and control of the COVID-19 outbreak. |
35 | 9griuata | What new public datasets are available related to COVID-19? | What we know so far: COVID-19 current clinical knowledge and research In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features , Copyright Notice (C) 2020 Royal College of Physicians |
29 | wbkn7yjh | 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? | Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses. |
28 | m9i9gu5g | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms [Image: see text] The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement. |
5 | l5q5wc06 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19) A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been 2 novel coronavirus outbreaks in the past 2 decades. The outbreak of severe acute respiratory syndrome (SARS) in 2002–2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 deaths), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features. |
42 | s26ehas6 | Does Vitamin D impact COVID-19 prevention and treatment? | Two-year outcomes on bone density and fracture incidence in patients with T2DM randomized to bariatric surgery versus intensive medical therapy. OBJECTIVE To determine the 2-year outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) vs. intensive medical therapy (IMT) on lean body mass, total bone mass, and bone mineral density (BMD) measures from the STAMPEDE trial. METHODS 54 subjects (BMI: 36 ± 1 kg/m(2) , age: 48 ± 4 years) with type 2 diabetes (T2DM) (HbA1c : 9.7 ± 2%) were randomized to IMT, RYGB, or SG and underwent DXA at baseline and at 1 and 2 years. RESULTS At 2 years, the reduction in BMI was similar after RYGB and SG and was greater than IMT (P < 0.001). Lean mass was reduced by ∼10%, total bone mineral content reduced by ∼8%, and hip BMD reduced by ∼9% in both surgical groups and was significantly greater than IMT despite increases in vitamin D intake in all groups. The change in hip BMD correlated with weight loss (r = 0.84, P < 0.0001) and changes in lean mass (r = 0.74, P < 0.0001) and leptin (r = 0.53, P < 0.0001). Peripheral fractures were self-reported in RYGB (4/18 patients), SG (2/19 patients), and IMT (4/16 patients). CONCLUSIONS Surgically induced weight loss is associated with modest reductions in lean mass, bone mineral content, and BMD, despite calcium and vitamin D supplementation in patients with T2DM. Awareness for bone loss is indicated for patients undergoing bariatric procedures. |
20 | pl6dpxkz | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury During several months of 2003, a newly identified illness termed severe acute respiratory syndrome (SARS) spread rapidly through the world(1,2,3). A new coronavirus (SARS-CoV) was identified as the SARS pathogen(4,5,6,7), which triggered severe pneumonia and acute, often lethal, lung failure(8). Moreover, among infected individuals influenza such as the Spanish flu(9,10) and the emergence of new respiratory disease viruses(11,12) have caused high lethality resulting from acute lung failure(13). In cell lines, angiotensin-converting enzyme 2 (ACE2) has been identified as a potential SARS-CoV receptor(14). The high lethality of SARS-CoV infections, its enormous economic and social impact, fears of renewed outbreaks as well as the potential misuse of such viruses as biologic weapons make it paramount to understand the pathogenesis of SARS-CoV. Here we provide the first genetic proof that ACE2 is a crucial SARS-CoV receptor in vivo. SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo that can be attenuated by blocking the renin-angiotensin pathway. These results provide a molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1267) contains supplementary material, which is available to authorized users. |
35 | 6bxr1wmv | What new public datasets are available related to COVID-19? | Inbetweening auto-animation via Fokker-Planck dynamics and thresholding We propose an equilibrium-driven deformation algorithm (EDDA) to simulate the inbetweening transformations starting from an initial image to an equilibrium image, which covers images varying from a greyscale type to a colorful type on plane or manifold. The algorithm is based on Fokker-Planck dynamics on manifold, which automatically cooperates positivity, unconditional stability, mass conservation law, exponentially convergence and also the manifold structure suggested by dataset. The thresholding scheme is adapted for the sharp interface dynamics and is used to achieve the finite time convergence. Using EDDA, three challenging examples, (I) facial aging process, (II) coronavirus disease 2019 (COVID-19) invading/treatment process, and (III) continental evolution process are conducted efficiently. |
3 | p4byrhlt | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum) in combination with rASP-1, a protein adjuvant, using the Middle East respiratory syndrome coronavirus MERS-CoV receptor-binding-domain (RBD) vaccine antigen. A highly enhanced anti-MERS-CoV neutralizing antibody response was induced when mice were immunized with rASP-1 and the alum-adjuvanted RBD vaccine in two separate injection sites as compared to mice immunized with RBD + rASP-1 + alum formulated into a single inoculum. The antibodies produced also significantly inhibited the binding of RBD to its cell-associated receptor. Moreover, immunization with rASP-1 co-administered with the alum-adjuvanted RBD vaccine in separate sites resulted in an enhanced frequency of TfH and GC B cells within the draining lymph nodes, both of which were positively associated with the titers of the neutralizing antibody response related to anti-MERS-CoV protective immunity. Our findings not only indicate that this unique combinatorial adjuvanted RBD vaccine regimen improved the immunogenicity of RBD, but also point to the importance of utilizing combinatorial adjuvants for the induction of synergistic protective immune responses. |
22 | 99q1bhba | are cardiac complications likely in patients with COVID-19? | Pharmacological and Biological Antiviral Therapeutics for Cardiac Coxsackievirus Infections Subtype B coxsackieviruses (CVB) represent the most commonly identified infectious agents associated with acute and chronic myocarditis, with CVB3 being the most common variant. Damage to the heart is induced both directly by virally mediated cell destruction and indirectly due to the immune and autoimmune processes reacting to virus infection. This review addresses antiviral therapeutics for cardiac coxsackievirus infections discovered over the last 25 years. One group represents pharmacologically active low molecular weight substances that inhibit virus uptake by binding to the virus capsid (e.g., pleconaril) or inactivate viral proteins (e.g., NO-metoprolol and ribavirin) or inhibit cellular proteins which are essential for viral replication (e.g., ubiquitination inhibitors). A second important group of substances are interferons. They have antiviral but also immunomodulating activities. The third and most recently discovered group includes biological and cellular therapeutics. Soluble receptor analogues (e.g., sCAR-Fc) bind to the virus capsid and block virus uptake. Small interfering RNAs, short hairpin RNAs and antisense oligonucleotides bind to and led to degradation of the viral RNA genome or cellular RNAs, thereby preventing their translation and viral replication. Most recently mesenchymal stem cell transplantation has been shown to possess antiviral activity in CVB3 infections. Taken together, a number of antiviral therapeutics has been developed for the treatment of myocardial CVB infection in recent years. In addition to low molecular weight inhibitors, biological therapeutics have become promising anti-viral agents. |
26 | nmh6luou | what are the initial symptoms of Covid-19? | Classification of the cutaneous manifestations of COVID‐19: a rapid prospective nationwide consensus study in Spain with 375 cases BACKGROUND: Cutaneous manifestations of COVID‐19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findings METHODS: Nationwide case collection survey of images and clinical data. Using a consensus, we described 5 clinical patterns. We later described the association of these patterns with patient demographics, timing in relation to symptoms of the disease, severity, and prognosis. RESULTS: Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize paucisymptomatic cases. |
40 | wbfi0v2x | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | The Role of a Geriatrician has Become Even More Important in an Academic Institution during COVID-19 |
18 | ppzxvykb | what are the best masks for preventing infection by Covid-19? | ELM—the database of eukaryotic linear motifs Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing protein localization. Given their importance, our understanding of motifs is surprisingly limited, largely as a result of the difficulty of discovery, both experimentally and computationally. The Eukaryotic Linear Motif (ELM) resource at http://elm.eu.org provides the biological community with a comprehensive database of known experimentally validated motifs, and an exploratory tool to discover putative linear motifs in user-submitted protein sequences. The current update of the ELM database comprises 1800 annotated motif instances representing 170 distinct functional classes, including approximately 500 novel instances and 24 novel classes. Several older motif class entries have been also revisited, improving annotation and adding novel instances. Furthermore, addition of full-text search capabilities, an enhanced interface and simplified batch download has improved the overall accessibility of the ELM data. The motif discovery portion of the ELM resource has added conservation, and structural attributes have been incorporated to aid users to discriminate biologically relevant motifs from stochastically occurring non-functional instances. |
2 | 38c28tw1 | how does the coronavirus respond to changes in the weather | Post-translational modifications of coronavirus proteins: roles and function Post-translational modifications (PTMs) refer to the covalent modifications of polypeptides after they are synthesized, adding temporal and spatial regulation to modulate protein functions. Being obligate intracellular parasites, viruses rely on the protein synthesis machinery of host cells to support replication, and not surprisingly, many viral proteins are subjected to PTMs. Coronavirus (CoV) is a group of enveloped RNA viruses causing diseases in both human and animals. Many CoV proteins are modified by PTMs, including glycosylation and palmitoylation of the spike and envelope protein, N- or O-linked glycosylation of the membrane protein, phosphorylation and ADP-ribosylation of the nucleocapsid protein, and other PTMs on nonstructural and accessory proteins. In this review, we summarize the current knowledge on PTMs of CoV proteins, with an emphasis on their impact on viral replication and pathogenesis. The ability of some CoV proteins to interfere with PTMs of host proteins will also be discussed. |
4 | 92ipp5ge | what causes death from Covid-19? | Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study Objective: Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented. Design: Retrospective population-based study. Setting: Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018. Participants: 5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020). Measurements: Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid19 patients and the corresponding mortality in the 2018 general population. Results: A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05). Limitations: Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified. Conclusions: Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19. |
15 | fozglfc8 | how long can the coronavirus live outside the body | Cytokine Storm Induced by SARS-CoV-2 A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response. |
37 | gquo184w | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Amino acid variation analysis of surface spike glycoprotein at 614 in SARS-CoV-2 strains Abstract As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains. |
28 | vxqdfiel | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Clinical trials on drug repositioning for COVID-19 treatment The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants' clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution. |
27 | 8o3l3rsf | what is known about those infected with Covid-19 but are asymptomatic? | Effectiveness of control strategies for Coronavirus Disease 2019: a SEIR dynamic modeling study Background: Since its first cases occurrence in Wuhan, China, the Coronavirus Disease 2019 (COVID-19) has been spreading rapidly to other provinces and neighboring countries. A series of intervention strategies have been implemented, but didn't stop its spread. Methods: Two mathematical models have been developed to simulate the current epidemic situation in the city of Wuhan and in other parts of China. Special considerations were given to the mobility of people for the estimation and forecast the number of asymptomatic infections, symptomatic infections, and the infections of super-spreading events (Isse). Findings: The basic reproductive number (R0) was calculated for the period between 18 January 2020 and 16 February 2020: R0 declined from 5.75 to 1.69 in Wuhan and from 6.22 to 1.67 in the entire country (not including the Wuhan area). At the same time, Wuhan is estimated to observe a peak in the number of confirmed cases around 6 February 2020. The number of infected individuals in the entire country (not including the Wuhan area) peaked around February 3. The results also show that the peak of new asymptomatic cases per day in Wuhan occurred on February 6, and the peak of new symptomatic infections have occurred on February 3. Concurrently, while the number of confirmed cases nationwide would continue to decline, the number of real-time COVID-19 inpatients in Wuhan has reached a peak of 13,030 on February 14 before it decreases. The model further shows that the COVID-19 cases will gradually wane by the end of April 2020, both in Wuhan and the other parts of China. The number of confirmed cases would reach the single digit on March 27 in Wuhan and March 19 in the entire country. The five cities with top risk index in China with the exclusion of Wuhan are: Huanggang, Xiaogan, Jingzhou, Chongqing, and Xiangyang city. Interpretations: Although the national peak time has been reached, a significant proportion of asymptomatic patients and the infections of super-spreading events (Isse) still exist in the population, indicating the potential difficulty for the prevention and control of the disease. As the Return-to-Work tide is approaching and upgrading, further measures (e.g., escalatory quarantine, mask wearing when going out, and sit apart when taking vehicles) will be particularly crucial to stop the COVID-19 in other cities outside of Wuhan. |
40 | g1zxlaer | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | The establishment of reference sequence for SARS-CoV-2 and variation analysis Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future. |
31 | vo755hxj | How does the coronavirus differ from seasonal flu? | Typical epidemiology of respiratory virus infections in a Brazilian slum Host population size, density, immune status, age structure, and contact rates are critical elements of virus epidemiology. Slum populations stand out from other settings and may present differences in the epidemiology of acute viral infections. We collected nasopharyngeal specimens from 282 children aged ≤5 years with acute respiratory tract infection (ARI) during 2005 to 2006 in one of the largest Brazilian slums. We conducted real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) for 16 respiratory viruses, nested RT‐PCR‐based typing of rhinoviruses (HRVs), and collected clinical symptoms. Viruses were common causes of respiratory disease; with ≥1 virus being detected in 65.2% of patients. We detected 15 different viruses during 1 year with a predomidnance of HRV (33.0%) and human respiratory syncytial virus (hRSV, 12.1%) infections, and a high rate of viral coinfections (28.3%). We observed seasonality of hRSV, HRV and human coronavirus infections, more severe symptoms in hRSV and influenza virus (FLU) infections and prolonged circulation of seven HRV clusters likely representing distinct serotypes according to genomic sequence distances. Potentially unusual findings included the absence of human metapneumovirus detections and lack of typical FLU seasonal patterns, which may be linked to the population size and density of the slum. Nonetheless, most epidemiological patterns were similar to other studies globally, suggesting surprising similarities of virus‐associated ARI across highly diverse settings and a complex impact of population characteristics on respiratory virus epidemiology. |
8 | jw2upelx | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Fighting the Coronavirus Outbreak |
5 | f9s46an9 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | State-of-the-art tools to identify druggable protein ligand of SARS-CoV-2 INTRODUCTION: The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2. MATERIAL AND METHODS: State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands. RESULTS: The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log P = 3.00; DG = –10.2567 kcal/mol; pKi = 7.713 µM) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log P = 2.901; DG = –12.2112 kcal/mol; pKi = 7.885 µM) of SARS-CoV-2. CONCLUSIONS: The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-of-the-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19. |
40 | b5y1xm2z | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Complexities of Viral Mutation Rates. Many viruses evolve rapidly. This is due, in part, to their high mutation rates. Mutation rate estimates for over 25 viruses are currently available. Here, we review the population genetics of virus mutation rates. We specifically cover the topics of mutation rate estimation, the forces that drive the evolution of mutation rates, and how the optimal mutation rate can be context-dependent. |
28 | ae8y9exx | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Potential antivirals and antiviral strategies against SARS coronavirus infections There are a number of antivirals as well as antiviral strategies that could be envisaged to prevent or treat severe acute respiratory syndrome (SARS) (or similar) coronavirus (CoV) infections. Targets for the prophylactic or therapeutic interventions include interaction of the spike (S) glycoprotein (S1 domain) with the host cell receptor, fusion of the S2 domain with the host cell membrane, processing of the replicase polyproteins by the virus-encoded proteases (3C-like cysteine protease [3CLpro] and papain-like cysteine protease) and other virus-encoded enzymes such as the NTPase/helicase and RNA-dependent RNA polymerase. Human monoclonal antibody blocking S1 may play an important role in the immunoprophylaxis of SARS. Fusion inhibitors reminiscent of enfuvirtide in the case of HIV may also be developed for SARS-CoV. Various peptidomimetic and nonpeptidic inhibitors of 3CLpro have been described, the best ones inhibiting SARS-CoV replication with a selectivity index greater than 1000. Human interferons, in particular α- and β-interferon, as well as short interfering RNAs could further be pursued for the control of SARS. Various other compounds, often with an ill-defined mode of action but selectivity indexes up to 100, have been reported to exhibit in vitro activity against SARS-CoV: valinomycin, glycopeptide antibiotics, plant lectins, hesperetin, glycyrrhizin, aurintricarboxylic acid, chloroquine, niclosamide, nelfinavir and calpain inhibitors. |
42 | yci0a6bt | Does Vitamin D impact COVID-19 prevention and treatment? | Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens Pregnancy-associatedPlasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show here that human monoclonal IgG antibodies with specificity for variant surface antigens (VSA) specifically expressed by CSA-adhering IEs (VSA(PAM)) can be used in vitro to select parasites from nonpregnant donors to express VSA(PAM) and that this selection for VSA(PAM) expression results in preferential transcription of var2csa. The results corroborate current efforts to develop PAM-specific vaccines based on VAR2CSA. |
16 | nni6l7n0 | how long does coronavirus remain stable on surfaces? | Long-term humoral immunity against viruses: revisiting the issue of plasma cell longevity Despite extensive documentation of prolonged antibody responses following vaccination or acute viral infection, the mechanisms behind long-term antibody production are not fully understood. We propose the hypothesis that long-lived plasma cells are an important, yet largely overlooked, component of long-term humoral immunity. |
10 | o8uk6if2 | has social distancing had an impact on slowing the spread of COVID-19? | Modeling, state estimation, and optimal control for the US COVID-19 outbreak The novel coronavirus SARS-CoV-2 and resulting COVID-19 disease have had an unprecedented spread and continue to cause an increasing number of fatalities worldwide. While vaccines are still under development, social distancing, extensive testing, and quarantining of confirmed infected subjects remain the most effective measures to contain the pandemic. These measures carry a significant socioeconomic cost. In this work, we introduce a novel optimization-based decision-making framework for managing the COVID-19 outbreak in the US. This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. The analysis of our extensive computational efforts reveals that social distancing and quarantining are most effective when implemented early, with quarantining of confirmed infected subjects having a much higher impact. Further, we find that "on-off" policies alternating between strict social distancing and relaxing such restrictions can be effective at "flattening" the curve while likely minimizing social and economic cost. |
25 | vsinwqnr | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations Summary As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill. |
37 | ax6v6ham | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Close relationship between SARS-coronavirus and group 2 coronavirus. The sudden appearance and potential lethality of severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in humans has resulted in a focusing of new attention on the determination of both its origins and evolution. The relationship existing between SARS-CoV and other groups of coronaviruses was determined via analyses of phylogenetic trees and comparative genomic analyses of the coronavirus genes: polymerase (Orf1ab), spike (S), envelope (E), membrane (M) and nucleocapsid (N). Although the coronaviruses are traditionally classed into 3 groups, with SARS-CoV forming a 4th group, the phylogenetic position and origins of SARS-CoV remain a matter of some controversy. Thus, we conducted extensive phylogenetic analyses of the genes common to all coronavirus groups, using the Neighbor-joining, Maximum-likelihood, and Bayesian methods. Our data evidenced largely identical topology for all of the obtained phylogenetic trees, thus supporting the hypothesis that the relationship existing between SARS-CoV and group 2 coronavirus is a monophyletic one. Additional comparative genomic studies, including sequence similarity and protein secondary structure analyses, suggested that SARS-CoV may bear a closer relationship with group 2 than with the other coronavirus groups. Although our data strongly suggest that group 2 coronaviruses are most closely related with SARS-CoV, further and more detailed analyses may provide us with an increased amount of information regarding the origins and evolution of the coronaviruses, most notably SARS-CoV. |
17 | 7yyanpoh | are there any clinical trials available for the coronavirus | COVID-19 in patients with HIV: clinical case series |
15 | tikjfp08 | how long can the coronavirus live outside the body | Resistance of Berne virus to physical and chemical treatment Thermal inactivation of Berne virus proceeded at a linear rate between 31°C and 43°C. Storage at temperatures lower than −20°C preserved the infectivity, while at 4°C appreciable loss occurred between 92 and 185 days. Freeze-drying or desiccation at 22°C caused only insignificant loss of infectivity. Virus preparations were not affected by pH values between 2.5 and 10.3. Inactivation by UV occurred more rapidly than with herpes, toga and rhabdoviruses. Berne virus infectivity was sensitive to pronase and B. subtilis proteinase. It was not inactivated by trypsin and chymotrypsin treatment, which resulted in enhancement of infectivity; low concentrations of pronase (< 10 μg ml(−1)) had a similar effect on Berne virus. Neither phospholipase C or RNase, alone or in combination, nor sodium deoxycholate (0.1%) inactivated the virus; in contrast, Triton X-100 (0.1%, 1.0%) caused rapid inactivation with a constant level of residual infectivity. |
17 | xb4ld4tr | are there any clinical trials available for the coronavirus | Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19 Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe COVID-19 might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19. |
45 | vzmlkk79 | How has the COVID-19 pandemic impacted mental health? | Mental Health Treatment for Front-Line Clinicians During and After the Coronavirus Disease 2019 (COVID-19) Pandemic: A Plea to the Medical Community The COVID-19 pandemic has placed front-line health care professionals—who were already at higher risk for negative effects of chronic stress before the pandemic—at even greater risk for depression and anxiety. This article reminds us of the importance of mutual support and caring for our own mental health, including seeking help from our mental health colleagues when needed. |
11 | emfubno8 | what are the guidelines for triaging patients infected with coronavirus? | The role of emergency medical services in containing COVID-19 |
19 | ti75rrwk | what type of hand sanitizer is needed to destroy Covid-19? | Taiwan's traffic control bundle and the elimination of nosocomial severe acute respiratory syndrome among healthcare workers Summary The traffic control bundle consists of procedures designed to help prevent epidemic nosocomial infection. We retrospectively studied the serial infection control measures to determine factors most effective in preventing nosocomial infections of healthcare workers (HCWs) during the 2003 Taiwanese severe acute respiratory syndrome (SARS) epidemic. Fever screening stations, triage of fever patients, separating SARS patients from other patients, separation of entrances and passageways between patients and HCWs, and increasing hand-washing facilities all demonstrated a protective effect for HCWs (univariate analysis; P <0.05). By multiple logistic regression: (i) checkpoint alcohol dispensers for glove-on hand rubbing between zones of risk, and (ii) fever screening at the fever screen station outside the emergency department, were the significant methods effectively minimising nosocomial SARS infection of HCWs (P <0.05). The traffic control bundle should be implemented in future epidemics as a tool to achieve strict infection control measures. |
39 | 8u685f45 | What is the mechanism of cytokine storm syndrome on the COVID-19? | SARS-CoV-2 infection: the role of cytokines in COVID-19 disease COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19. |
11 | ima51d0x | what are the guidelines for triaging patients infected with coronavirus? | Development of a Palliative Care Toolkit for the COVID-19 Pandemic The COVID-19 pandemic has led to high numbers of critically ill and dying patients in need of expert management of dyspnea, delirium, and serious illness communication. The rapid spread of SARS-CoV-2 creates surges of infected patients requiring hospitalization and puts palliative care programs at risk of being overwhelmed by patients, families, and clinicians seeking help. In response to this unprecedented need for palliative care, our program sought to create a collection of palliative care resources for non-palliative care clinicians. A workgroup of interdisciplinary palliative care clinicians developed the Palliative Care Toolkit, consisting of a detailed chapter in a COVID-19 online resource, a mobile and desktop web application, one-page guides, pocket cards, and communication skills training videos. The suite of resources provides expert and evidence-based guidance on symptom management including dyspnea, pain, and delirium, and also on serious illness communication, including conversations about goals of care, code status, and end-of-life. We also created a nurse resource hotline staffed by palliative care nurse practitioners and virtual office hours staffed by a palliative care attending physician. Since its development, the Toolkit has helped us disseminate best practices to non-palliative care clinicians delivering primary palliative care, allowing our team to focus on the highest-need consults, and increasing acceptance of palliative care across hospital settings. |
26 | i2mw9289 | what are the initial symptoms of Covid-19? | (18)F-FDG PET/CT and Serial Chest CT Findings in a COVID-19 Patient With Dynamic Clinical Characteristics in Different Period Neurological symptoms and gastrointestinal symptoms were rare at onset in COVID-19. Here we report a 37-year-old man with vertigo, fever, and diarrhea symptoms as the first manifestation. (18)F-FDG PET/CT spotted multiple ground glass opacity (GGO) lesions in the lungs, with increased tracer uptake in both lung GGOs and the whole colon. Serial CT examinations showed the emersion and dissipation of lung GGOs. We illustrate the symptoms initiation, the laboratory test results, the imaging examination, and the treatment strategy in the duration of COVID-19 with a timeline chart. |
39 | xxvrt41o | What is the mechanism of cytokine storm syndrome on the COVID-19? | Calming Cytokine Storm in Pneumonia by Targeted Delivery of TPCA-1 Using Platelet-derived Extracellular Vesicles Summary Pneumonia can cause high morbidity and mortality due to the uncontrolled inflammation in the lung tissue. Calming the cytokine storm may be one key to save the life of patients with severe pneumonia. Here, inspired by the intrinsic affinity of platelets to the site of inflammation, we have engineered platelet-derived extracellular vesicles (PEVs) for pneumonia-targeted drug delivery. It is demonstrated that PEVs that are easily generated from the activated platelets can selectively target pneumonia in the mice model with acute lung injury (ALI). By loading with [5-(p-Fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1) that can inhibit the production of inflammatory factors, the PEVs significantly improve therapeutic benefits by inhibiting the pulmonary inflammatory cells infiltration, and calming local cytokine storm compared with the free drug-treated group. Furthermore, we find that PEVs could serve as a broad platform that can selectively target various inflammatory sites, including chronic atherosclerotic plaque, rheumatoid arthritis and wound associated with skin. |
38 | 2xnq1oq7 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care OBJECTIVE: Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. METHODS: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). RESULTS: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. CONCLUSION: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key. |
19 | bp6st31f | what type of hand sanitizer is needed to destroy Covid-19? | Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses. |
16 | 9204b4mx | how long does coronavirus remain stable on surfaces? | Diagnostic methods and potential portable biosensors for coronavirus disease 2019 Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. Various specimens for diagnosis or detection are compared and analyzed. Among them, deep throat saliva and induced sputum are desired for RT-qPCR test or other early detection technologies. Chest computerized tomography (CT) scan, RT-qPCR, lateral flow immunochromatographic strip (LFICS) for diagnosis of COVID-19 are summarized and compared. Specially, potential electrochemical biosensor, surface enhanced Raman scattering (SERS)-based biosensor, and artificial intelligence (AI) assisted diagnosis of COVID-19 are emphasized. Finally, some commercialized portable detection device, current challenges and future directions are discussed. |
30 | phxu6usy | is remdesivir an effective treatment for COVID-19 | A search for medications to treat COVID-19 via in silico molecular docking models of the SARS-CoV-2 spike glycoprotein and 3CL protease BACKGROUND: The COVID-19 has now been declared a global pandemic by the World Health Organization. There is an emergent need to search for possible medications. METHOD: Utilization of the available sequence information, homology modeling, and in slico docking a number of available medications might prove to be effective in inhibiting the SARS-CoV-2 two main drug targets, the spike glycoprotein, and the 3CL protease. RESULTS: Several compounds were determined from the in silico docking models that might prove to be effective inhibitors for SARS-CoV-2. Several antiviral medications: Zanamivir, Indinavir, Saquinavir, and Remdesivir show potential as and 3CLPRO main proteinase inhibitors and as a treatment for COVID-19. CONCLUSION: Zanamivir, Indinavir, Saquinavir, and Remdesivir are among the exciting hits on the 3CLPRO main proteinase. It is also exciting to uncover that Flavin Adenine Dinucleotide (FAD) Adeflavin, B2 deficiency medicine, and Coenzyme A, a coenzyme, may also be potentially used for the treatment of SARS-CoV-2 infections. The use of these off-label medications may be beneficial in the treatment of the COVID-19. |
23 | hzq8pkr5 | what kinds of complications related to COVID-19 are associated with hypertension? | Cardiovascular disease and COVID-19: les liaisons dangereuses Patients with cardiovascular risk factors or established cardiovascular disease have an increased risk of developing coronavirus disease 19 and have a worse outcome when infected, but translating this notion into effective action is challenging. At present it is unclear whether cardiovascular therapies may reduce the likelihood of infection, or improve the survival of infected patients. Given the crucial importance of this issue for clinical cardiologists and all specialists dealing with coronavirus disease 19, we tried to recapitulate the current evidence and provide some practical recommendations. |
22 | 8hj06hzt | are cardiac complications likely in patients with COVID-19? | Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and PBPK model Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used in treating COVID-19 patients recently. However, both drugs have some contradictions and rare but severe side effects, such as hypoglycemia, retina and cardiac toxicity. To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in 8 cell lines, and further adopted the physiologically-based pharmacokinetic models (PBPK) to predict the tissue risk respectively. Retina, myocardium, lung, liver, kidney, vascular endothelium and intestinal epithelium originated cells were included in the toxicity evaluation of CQ and HCQ respectively. The proliferation pattern was monitored in 0-72 hours by IncuCyte S3, which could perform long-term continuous image and video of cells upon CQ or HCQ treatment. CC50 and the ratio of tissue trough concentrations to CC50 (RTTCC) were brought into predicted toxicity profiles. The CC50 at 24 h, 48 h, 72 h of CQ and HCQ decreased in the time-dependent manner, which indicates the accumulative cytotoxic effect. HCQ was found to be less toxic in 7 cell types except cardiomyocytes H9C2 cells (CC50-48 h=29.55 μM; CC50-72 h=15.26 μM). In addition, RTTCC is significant higher in CQ treatment group compared to HCQ group, which indicates that relative safety of HCQ. Both CQ and HCQ have certain cytotoxicity in time dependent manner which indicates the necessity of short period administration clinically. HCQ has the less impact in 7 cell lines proliferation and less toxicity compared to CQ in heart, liver, kidney and lung. |
21 | earli6ww | what are the mortality rates overall and in specific populations | Letalidad del COVID-19: ausencia de patrón epidemiológico ABSTRACT Objective: Analyze a set of indicators to understand the variability of the evolution and impact of the COVID-19 epidemic in a set of selected countries. Method: Ecological study of a group of countries with more than 200 reported cases. Demographic variables, health expenditure variables, and variables about characteristics of health services were included as explanatory variables. and incidence, mortality and fatality rates have been analyzed as response variables. In addition, a relative fatality index has been created. Data are from international organizations. Spearman's correlation coefficient was used to estimate the magnitude of the associations. Results: Number of tests and of medical professionals are associated with a higher incidence rate. Mortality and case fatality rate are not associated with demographic, health expenditure, or health services variables. Conclusion: Differences suggest a general underestimation of the magnitude of the epidemic. Improvement of case identification and effectiveness of epidemiological surveillance systems is necessary. |
22 | w2huxj8q | are cardiac complications likely in patients with COVID-19? | Impact of Cardiovascular Disease on Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19) BACKGROUND: To investigate the effect of cardiovascular disease (CVD) on the global pandemic, coronavirus disease 2019 (COVID-19), we analyzed the cases of laboratory-confirmed COVID-19 patients in Wuhan.Methods and Results:Data were extracted from the medical records. SARS-CoV-2 RNA was confirmed by RT-PCR. A total of 33 (53.2%) of 62 cases with CVD, who had higher prevalence of severe COVID-19 compared with non-CVD patients (P=0.027). The median age of all patients was 66.0 (53.3, 73.0) years old. Coronary artery disease (11.3%) and hypertension (38.7%) were the common coexisting CVDs in COVID-19 patients. High-sensitivity cardiac troponin I (hs-cTnI), creatinine, high-density lipoprotein-cholesterol, interleukin-6, C-reactive protein, prothrombin time, and D-dimer levels in the severe COVID-19 with CVD group were higher than in the non-severe COVID-19 with CVD group (P<0.05). For all patients, chest computed tomography (CT) showed ground-glass opacity (66.1%), local (21.0%), bilateral (77.4%), and interstitial abnormalities (4.8%). In COVID-19 patients with CVD, 27 (81.8%) were cured and discharged. 6 (18.2%) remained in hospital, including 2 (3.2%) patients requiring intubation and mechanical ventilation. The hs-cTnI levels in the remaining hospitalized patients were higher than in the discharged patients (P=0.047). CONCLUSIONS: CVDs play a vital role in the disease severity of COVID-19. COVID-19 could result in myocardial injury, which affects the prognosis of COVID-19. |
15 | 7ftq02ev | how long can the coronavirus live outside the body | How long does Coronavirus survive on different surfaces? Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices |
6 | a6mdyq85 | what types of rapid testing for Covid-19 have been developed? | Comparison of Cepheid Xpert Xpress and Abbott ID Now to Roche cobas for the Rapid Detection of SARS-CoV-2 BACKGROUND: The SARS-CoV-2 pandemic has created an urgent and unprecedented need for rapid large-scale diagnostic testing to inform timely patient management. However, robust data are lacking on the relative performance of available rapid molecular tests across a full range of viral concentrations. OBJECTIVE: This study aimed to compare two recently-authorized rapid tests, Cepheid Xpert Xpress SARS-CoV-2 and Abbott ID Now SARS-CoV-2, to the Roche cobas SARS-CoV-2 assay for samples with low, medium, and high viral concentrations. STUDY DESIGN: A total of 113 nasopharyngeal swabs from remnant patient samples were tested, including 88 positives spanning the full range of observed Ct values on the cobas assay. RESULTS: Compared to cobas, the overall positive agreement was 73.9% with ID Now and 98.9% with Xpert. Negative agreement was 100% and 92.0% for ID Now and Xpert, respectively. Both ID Now and Xpert showed 100% positive agreement for medium and high viral concentrations (Ct value <30). However, for Ct values >30, positive agreement was 34.3% for ID Now and 97.1% for Xpert. CONCLUSIONS: While Xpert showed high agreement with cobas across a wide range of viral concentrations, this study highlights an important limitation of ID Now for specimens collected in viral or universal transport media with low viral concentrations. Further studies are needed to evaluate the performance of ID Now for direct swabs. |
3 | sxy4vl4b | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | An anterior mediastinal mass: delayed airway compression and using a double lumen tube for airway patency. Perioperative management of patients with an anterior mediastinal mass is difficult. We present a 35-year-old woman who showed delayed compression of the carina and left main bronchus despite no preoperative respiratory signs, symptoms, or radiologic findings due to an anterior mediastinal mass and uneventful stepwise induction of general anesthesia. Even use of a fiberoptic bronchoscope (FB) after induction of anesthesia was not helpful to predict delayed compression of the airway. Therefore, the anesthesiologist and the cardiothoracic surgeon must prepare for unexpected delayed compression of the airway, even in low risk patients who are asymptomatic or mildly symptomatic without postural symptoms or radiographic evidence of significant compression of structures. We also describe successful management for the compressed carina and left main bronchus with a double lumen tube (DLT) as a stent during surgery. FB guided DLT intubation is a possible solution to maintain airway patency. |
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