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7 | 2r9jlejw | are there serological tests that detect antibodies to coronavirus? | Rapid response flow cytometric assay for the detection of antibody responses to SARS-CoV-2 SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing a serious pandemic. While reliable nucleic acid-based diagnostic assays were rapidly available, there exists only a limited number of validated serological assays. Here, we evaluated a novel flow cytometric approach based on antigen-expressing HEK 293T cells to assess spike-specific IgG and IgM antibody responses. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA systems, while also revealing the highest sensitivity in specimens from PCR-confirmed SARS-CoV-2 infected patients. Additionally, a soluble Angiotensin-Converting-Enzyme 2 (ACE-2) variant was established as external standard to quantify spike-specific antibody responses on different assay platforms. In conclusion, our newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies, which can be easily adopted in different laboratories and does not rely on external supply of assay kits. |
14 | d0s028wl | what evidence is there related to COVID-19 super spreaders | SARS‐CoV‐2 and human milk: What is the evidence? The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed. |
7 | 7r6m6f6c | are there serological tests that detect antibodies to coronavirus? | Human rhinovirus C: a newly discovered human rhinovirus species Although often ignored, human rhinoviruses (HRVs) are the most frequent causes of respiratory tract infections (RTIs). A group of closely related novel rhinoviruses have recently been discovered. Based on their unique phylogenetic position and distinct genomic features, they are classified as a separate species, HRV-C. After their discovery, HRV-C viruses have been detected in patients worldwide, with a reported prevalence of 1.4–30.9% among tested specimens. This suggests that the species contribute to a significant proportion of RTIs that were unrecognized in the past. HRV-C is also the predominant HRV species, often with a higher detection rate than that of the two previously known species, HRV-A and HRV-B. HRV-C infections appear to peak in fall or winter in most temperate or subtropical countries, but may predominate in the rainy season in the tropics. In children, HRV-C is often associated with upper RTIs, with asthma exacerbation and wheezing episodes being common complications. The virus has also been detected in children with bronchitis, bronchiolitis, pneumonia, otitis media, sinusitis and systemic infections complicated by pericarditis. As for adults, HRV-C has been associated with more severe disease such as pneumonia and exacerbation of chronic obstructive pulmonary disease. However, larger clinical studies with asymptomatic controls are required to better define the significance of HRV-C infection in the adult population. On the basis of VP4 sequence analysis, a potential distinct subgroup within HRV-C has also been identified, although more complete genome sequences are needed to better define the genetic diversity of HRV-C. |
22 | usq41tnk | are cardiac complications likely in patients with COVID-19? | STEMI care during COVID-19: losing sight of the forest for the trees [Figure: see text] |
21 | ir77zvrr | what are the mortality rates overall and in specific populations | Viet Nam. Attention in this discussion of Viet Nam focuses on the following: history of the demographic situation; the government's overall approach to population problems; population data systems and development planning; institutional arangements for the integration of population within development planning; the government's view of the importance of population policy in achieving development objectives; population size, growth, and natural increase; morbidity and mortality; fertility; international migration; and spatial distribution. Relatively little information has been available on demographic trends in Viet Nam due to the absence of any major survey or census until the last few decades. The government increasingly has been concerned about the high rate of population growth and is working to change the situation through programs directed at fertility reduction. As part of its program for overall social and economic restructuring, the government seeks to give special attention to health problems, particularly those relating to maternal and child health and environmental sanitation. Population censuses in Viet Nam have been undertaken only in the last 2 decades, with censuses conducted in the North in 1960 and 1974. No population census was undertaken in the South, and any population information available was based upon the periodic population and household surveys conducted alternately in different provinces, cities, and rural areas during 1962, 1967, 1971, and 1974. The government considers the formulation and implementation of population policy to be a critical variable for realizing national development objectives. The population of Viet Nam has grown considerably since the 1950s, increasing from over 30 million in 1950 to 35.4 million in 1960 and reaching 43.1 million by 1970, according to UN estimates. 1979 census results indicate that the population of Viet Nam had reached 52.7 million. The current rate of growth is estimated at 2.2%. The government perceives the current rate of population growth as unsatisfactory because it is too high. The official government policy is to take steps to reduce the rate of population growth as rapidly as possible. All 3 demographic factors--mortality, fertility, and spatial distribution--are viewed as subject to direct policy intervention to achieve this goal. Rates of morbidity and mortality have declined considerably in the past few decades. The government reports a decline in the crude death rate from 12.2 in 1957 to 7.0 in 1980 and an increase in the life expectancy at birth from 34 years in 1936 to 60 in 1978. UN estimates are considerably higher. According to UN estimates, the infant mortality rate was 90.3/1000 live births during 1975-80 for Viet Nam as a whole. The current mortality and morbidity situation is considered to be unacceptable. The government estimates the crude birthrate as 29.3/1000 in 1980, an unsatisfactory level. The government perceives the present levels and trends of immigration as not significant and satisfactory and the spatial distribution as inappropriate. |
39 | tweqxttb | What is the mechanism of cytokine storm syndrome on the COVID-19? | Neutrophil calprotectin identifies severe pulmonary disease in COVID-19 Severe cases of coronavirus disease 2019 (COVID-19) are regularly complicated by respiratory failure. While it has been suggested that elevated levels of blood neutrophils associate with worsening oxygenation in COVID-19, it is unknown whether neutrophils are drivers of the thrombo-inflammatory storm or simple bystanders. We now report that patients with COVID-19 (n=96) have markedly elevated levels of the neutrophil activation marker S100A8/A9 (calprotectin) in their blood. Calprotectin tracked with other acute phase reactants including C-reactive protein, D-dimer, ferritin, and absolute neutrophil count, but was superior in identifying patients requiring mechanical ventilation. In longitudinal samples, calprotectin rose as oxygenation worsened. When tested on day 1 or 2 of hospitalization (n=52 patients), calprotectin levels were significantly higher in patients who progressed to severe COVID-19 requiring mechanical ventilation (7805 +/- 7585, n=23) as compared to those who remained free of intubation (3123 +/- 2990, p=0.0059). In summary, serum calprotectin levels track closely with current and future COVID-19 severity, strongly implicating neutrophils as active perpetuators of inflammation and respiratory compromise in COVID-19. |
34 | axddll4d | What are the longer-term complications of those who recover from COVID-19? | Comment on "Hearing loss and COVID-19: A note" |
50 | ma5fr966 | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | The current update of vaccines for SARS-COV-2 Late 2019 witnessed the appearance of coronavirus disease 2019 (COVID-19) outbreak triggered by a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 spread across China from Wuhan and has been circulated to a broader variety of countries. Seeing that COVID-19 has caused tremendous human casualties posing a global danger, an awareness of the current situation and the strategies to curtail the spread of the virus are desperately required. As the most natural way to preserve public wellbeing, preventive and therapeutic vaccinations must have essential roles. Large organizations and companies have started implementing SARS-CoV-2 preventive vaccinations. Hence, in this study, we aimed to update the vaccine evolution for SARS-CoV-2. |
41 | phmd0u6d | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Willingness to seek laboratory testing for SARS-CoV-2 with home, drive-through, and clinic-based specimen collection locations BACKGROUND: SARS-CoV-2 virus testing for persons with COVID-19 symptoms, and contact tracing for those testing positive, will be critical to successful epidemic control. Willingness of persons experiencing symptoms to seek testing may determine the success of this strategy. METHODS: A cross-sectional, online survey in the United States measured willingness to seek testing if feeling ill under different specimen collection scenarios: home-based saliva, home-based swab, drive-through facility swab, and clinic-based swab. Instructions clarified that home-collected specimens would be mailed to a laboratory for testing. We presented similar willingness questions regarding testing during follow-up care. RESULTS: Of 1435 participants, comprising a broad range of sociodemographic groups, 92% were willing to test with a home saliva specimen, 88% with home swab, 71% with drive-through swab, and 60% with clinic collected swab. Moreover, 68% indicated they would be more likely to get tested if there was a home testing option. There were no significant differences in willingness items across sociodemographic variables or for those currently experiencing COVID-19 symptoms. Results were nearly identical for willingness to receive testing for follow-up COVID-19 care. CONCLUSIONS: We observed a hierarchy of willingness to test for SARS-CoV-2, ordered by the degree of contact required. Home specimen collection options could result in up to one-third more symptomatic persons seeking testing, facilitating contact tracing and optimal clinical care. Remote specimen collection options may ease supply chain challenges and decrease the likelihood of nosocomial transmission. As home specimen collection options receive regulatory approval, they should be scaled rapidly by health systems. |
41 | ipbun60h | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | COVID-19 and mental health equity in the United States |
19 | 2x2ewsp8 | what type of hand sanitizer is needed to destroy Covid-19? | Ozone disinfectants like soclean CPAP sanitizer can be used to sterilize cloth and n95 masks in the protection against COVID-19 |
40 | c7j2eoz0 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Predicting the receptor-binding domain usage of the coronavirus based on kmer frequency on spike protein |
24 | ptnmtvzj | what kinds of complications related to COVID-19 are associated with diabetes | Effectiveness and safety of antiviral or antibody treatments for coronavirus: A rapid review Background: To identify safe and effective medical countermeasures (e.g., antivirals/antibodies) to address the current outbreak of a novel coronavirus (COVID-19) Methods: Comprehensive literature searches were developed by an experienced librarian for MEDLINE, EMBASE, the Cochrane Library, and biorxiv.org/medrxiv.org; additional searches for ongoing trials and unpublished studies were conducted in clinicaltrials.gov and the Global Infectious Diseases and Epidemiology Network (GIDEON). Title/abstract and full-text screening, data abstraction, and risk of bias appraisal were carried out by single reviewers. Results: 54 studies were included in the review: three controlled trials, 10 cohort studies, seven retrospective medical record/database studies, and 34 case reports or series. These studies included patients with severe acute respiratory syndrome (SARs, n=33), middle east respiratory syndrome (MERS, n=16), COVID-19 (n=3), and unspecified coronavirus (n=2). The most common treatment was ribavirin (n=41), followed by oseltamivir (n=10) and the combination of lopinavir/ritonavir (n=7). Additional therapies included broad spectrum antibiotics (n=30), steroids (n=39) or various interferons (n=12). No eligible studies examining monoclonal antibodies for COVID-19 were identified. One trial found that ribavirin prophylactic treatment statistically significantly reduced risk of MERS infection in people who had been exposed to the virus. Of the 21 studies reporting rates of ICU admission in hospitalized SARS or MERS patients, none reported statistically significant results in favour of or against antiviral therapies. Of the 40 studies reporting mortality rates in hospitalized SARS or MERS patients, one cohort study (MERS) and one retrospective study (SARS) found a statistically significant increase in the mortality rate for patients treated with ribavirin. Eighteen studies reported potential drug-related adverse effects including gastrointestinal symptoms, anemia, and altered liver function in patients receiving ribavirin. Conclusion: The current evidence for the effectiveness and safety of antiviral therapies for coronavirus is inconclusive and suffers from a lack of well-designed prospective trials or observational studies, preventing any treatment recommendations from being made. However, it is clear that the existing body of evidence is weighted heavily towards ribavirin (41/54 studies), which has not shown conclusive evidence of effectiveness and may cause harmful adverse events so future investigations may consider focusing on other candidates for antiviral therapy. |
17 | up5vftj4 | are there any clinical trials available for the coronavirus | Viral Infections |
7 | yy4bnb4o | are there serological tests that detect antibodies to coronavirus? | Detection of antibodies against SARS‐CoV‐2 in patients with COVID‐19 Detection of IgM and IgG against SARS-CoV-2 is a fast and simple screening method. As an effective supplement to RNA testing, antibody detection is of epidemiological significance and an important means to understand the occurrence, development, prognosis, and outcome of COVID-19. However, more medical research is needed on the expression level of antibodies against SARS-CoV-2 and the prognosis of COVID-19. This article is protected by copyright. All rights reserved. |
5 | 0slywdik | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines. |
22 | ynel6ore | are cardiac complications likely in patients with COVID-19? | Cardiovascular disease in COVID-19: a systematic review and meta-analysis of 10,898 patients and proposal of a triage risk stratification tool BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has drastically affected global health. Despite several studies, there is yet a dearth of data regarding the mechanisms of cardiac injury, clinical presentation, risk factors, and treatment of COVID-19-associated cardiovascular disease. This systematic review and meta-analysis is aimed at defining the clinical, electrocardiographic, and pathologic spectrum of cardiovascular disease (CVD), frequency of elevated cardiac and inflammatory biomarkers, and their frequency and relationship with severity of the disease and mortality in COVID-19 patients and to develop a triage risk stratification tool (TRST) that can serve as a guide for the timely recognition of the high-risk patients and mechanism-targeted therapy. We conducted an online search in databases of PubMed and Embase to identify relevant studies. Data selection was in concordance with PRISMA guidelines. Results were presented as pooled frequencies, odds ratio, standardized mean difference (SMD), and forest and funnel plots. RESULTS: We gathered a total of 54 studies and included 35 of them in our meta-analysis. Acute cardiac injury occurred in more than 25% of cases, mortality was 20 times higher, and admission to intensive care unit increased by 13.5 times. Hypertension was the most common pre-existing comorbidity with a frequency of 29.2%, followed by diabetes mellitus (13.5%). The deceased group of patients had higher cardiac and inflammatory biomarkers, with statistically significant SMD, compared with survivors. Pediatric patients were predominantly mildly affected. However, less frequently, the presentation was very similar to Kawasaki disease or Kawasaki shock syndrome. This latter presentation hass been called as multisystem inflammatory syndrome in children (MIS-C). CONCLUSIONS: There is a wide spectrum of cardiac involvement in COVID-19 patients, and hence a Triage Risk Stratification Tool can serve as a guide for the timely recognition of the high-risk patients and mechanism-targeted therapy. |
14 | z3dc5f1y | what evidence is there related to COVID-19 super spreaders | The December 2019 New Corona Virus (SARS-CoV-2) Outbreak: A Behavioral Infectious Disease Policy Model It is critical to understand the impact of distinct policy interventions to the ongoing December 2019 coronavirus (SARS-CoV-2) pandemic. We develop a flexible behavioral, dynamic, and sectorial epidemic policy model comprising both endogenous virus transmission and public health and citizen responses. Applicable to the full epidemic cycle including resurgence, the model allows exploring the multivariate impact of distinct policy interventions, including general and targeted testing and social contact reduction efforts. Calibrating the model to the early SARS-CoV-2 outbreak at the level of continents, we demonstrate how early, rapid, and extensive buildup of testing and social contact reduction efforts interplay to suppress the outbreak. Next, applying the model within hypothetical contexts we demonstrate how: i) sociodemographic variation in vulnerability to the virus affects overall reported and actual outbreak patterns; ii) feasible timing of deconfinement depends on earlier responses to the outbreak; and, iii) targeted approaches help suppress resurgent outbreaks and their various impacts. Finally, given the importance of broad support of outbreak control efforts, across public health experts, policymakers, volunteers, media, and citizens, we make the model also accessible in the form of a free web-based management flight simulator. |
21 | 0lyxvex0 | what are the mortality rates overall and in specific populations | Study of knowledge, attitude, anxiety & perceived mental healthcare need in Indian population during COVID-19 pandemic Abstract Novel Corona Virus Disease (COVID-19) originating from China has rapidly crossed borders, infecting people throughout the whole world. This phenomenon has led to a massive public reaction; the media has been reporting continuously across borders to keep all informed about the pandemic situation. All these things are creating a lot of concern for people leading to heightened levels of anxiety. Pandemics can lead to heightened levels of stress; Anxiety is a common response to any stressful situation. This study attempted to assess the knowledge, attitude, anxiety experience, and perceived mental healthcare need among adult Indian population during the COVID-19 pandemic. An online survey was conducted using a semi-structured questionnaire using a non-probability snowball sampling technique. A total of 662 responses were received. The responders had a moderate level of knowledge about the COVID-19 infection and adequate knowledge about its preventive aspects. The attitude towards COVID-19 showed peoples' willingness to follow government guidelines on quarantine and social distancing. The anxiety levels identified in the study were high. More than 80 % of the people were preoccupied with the thoughts of COVID-19 and 72 % reported the need to use gloves, and sanitizers. In this study, sleep difficulties, paranoia about acquiring COVID-19 infection and distress related social media were reported in 12.5 %, 37.8 %, and 36.4 % participants respectively. The perceived mental healthcare need was seen in more than 80 % of participants. There is a need to intensify the awareness and address the mental health issues of people during this COVID-19 pandemic. |
18 | 732f6u3t | what are the best masks for preventing infection by Covid-19? | Strategies to halt 2019 novel coronavirus (COVID‐19) spread for organ transplantation programs at the Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, China During the coronavirus outbreak in China, our center performed 16 organ transplants (10 kidney, 4 liver and 2 lung transplants, from January 24 to March 11, 2020) harvested from deceased donors. Regarding the strategies to prevent infections of COVID‐19, we implemented specific measures for the donor and recipient management, as well as prevention of hospital‐acquired infections. All 16 organ recipients had a favorable outcome without COVID‐19 infection. Our approaches aiming to interrupt the spread of coronavirus within the transplantation wards were successful and allowed us to maintain the transplantation program for deceased liver, kidney and lung recipients. |
44 | w574amkw | How much impact do masks have on preventing the spread of the COVID-19? | COVID-19 AND THE GLOBAL IMPACT ON COLORECTAL PRACTICE AND SURGERY BACKGROUND: The novel SARS-Cov-2 virus that emerged in December 2019 causing the COVID-19 disease has led to sudden national reorganization and delivery of health care systems globally. The purpose of this survey was to assess the global impact of the coronavirus on the delivery of colorectal practice and surgery. Materials & Method: A panel of International Society of University Colon & Rectal Surgeons selected 22 questions that were included into a questionnaire. The questionnaire was distributed electronically to ISUCRS fellows, other surgeons on our database and on social media. The questionnaire remained open from April 16-28, 2020. RESULTS: 287 surgeons completed the survey. 90% were colorectal specialists or general surgeons with an interest in colorectal diseases. COVID-19 had impacted the practice of 96% surgeons and 52% were now using telemedicine. 66% stated that elective colorectal cancer surgery (ECCS) could proceed but with perioperative precautions. 19.5% of respondents stated that provision of personal protection equipment was the most important perioperative precaution, however, this was only being provided in 9.1% of hospitals. 64% of surgeons were offering minimally invasive surgery, however, 44% stated that there was not enough information about the safety of loss of intrabdominal CO2 gas during the COVID-19 pandemic. 61% of surgeons were prepared to defer ECCS, with 29% willing to defer for up to 8 weeks. CONCLUSIONS: Our survey has demonstrated that globally COVID-19 has affected the ability of colorectal surgeons to offer care to practice. Various practical adaptation strategies have been discussed in this manuscript. |
12 | q99n2gqp | what are best practices in hospitals and at home in maintaining quarantine? | Telehealth Transformation: COVID-19 and the rise of Virtual Care The novel coronavirus disease-19 (COVID-19) pandemic has altered our economy, society and healthcare system. While this crisis has presented the US healthcare delivery system with unprecedented challenges, the pandemic has catalyzed rapid adoption of telehealth or the entire spectrum of activities used to deliver care at a distance. Using examples reported by US healthcare organizations including ours, we describe the role telehealth has played in transforming healthcare delivery during the three phases of the US COVID-19 pandemic: 1) Stay-at-Home Outpatient Care; 2) Initial COVID-19 Hospital Surge, and 3) Post-Pandemic Recovery. Within each of these three phases, we examine how people, process and technology work together to support a successful telehealth transformation. Whether healthcare enterprises are ready or not, the new reality is that virtual care has arrived. |
21 | 4yihgo8u | what are the mortality rates overall and in specific populations | Assumptions for disparities in case-fatality rates of coronavirus disease (COVID-19) across the globe. In a short span, Coronavirus disease (COVID-19) has become the world pandemic by rapidly spreading almost to all the countries around the globe, irrespective of the continent, population size, economic status and healthcare system. Despite the number of cases increasing exponentially in most of the countries, there exist certain disparities in terms of case-fatality rates. As of April 24, 2020, the case-fatality rate of COVID-19 is about 7.0%, with 193,671 deaths and 2,761,121 confirmed cases around the world. Although the United States of America (USA), Spain, Italy, France, and Germany are the top-most affected counties in terms of confirmed cases; France, Italy and Spain are leading the list in terms of case-fatality rates. Therefore, through this mini-review, authors sought to brief on possible assumptions (five D's) that might contribute to the varying case-fatality rates among different countries across the globe. |
34 | iwsa760n | What are the longer-term complications of those who recover from COVID-19? | Systematic Review of the Registered Clinical Trials of Coronavirus Disease 2019 (COVID-19) Background: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have immediately carried out clinical research scheme of the COVID-19. But, there is still a lack of systematic review of registered clinical trials. Therefore, we conducted a systematic review of the clinical trials of COVID-19 to summarize the characteristics of the COVID-19 registered clinical trials. Methods: This study is based on the recommendations of the PRISMA in the Cochrane handbook. The databases from the Chinese Clinical Registration Center and the ClinicalTrials.gov were searched to collect the registered clinical trials of COVID-19. The retrieval inception date is February 9, 2020. Two researchers independently selected the literature based on inclusion and exclusion criteria, extracted data and evaluated the risk of bias. Results: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) of COVID-19 were obtained. A majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials had been completed; 34 trials were early clinical exploratory trials or in a pre-experiment stage, 15 trials belonged to phrase Ⅲ and 4 trials were phrase Ⅳ. The methods of intervention included traditional Chinese medicine involving 26 trials, Western medicine involving 30 trials, and integrated traditional Chinese medicine and Western medicine involving 19 trials. The subjects were mainly non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60 - 200), and the median execute time of the trials was 179 d (IQR: 94 - 366 d). The main outcomes were clinical observation and examinations. Overall, both the methodology quality of interventional trials and observational studies were low. Conclusions: Disorderly and intensive clinical trials of COVID-19 using traditional Chinese medicine and western medicine are ongoing or will being carried out in China. However, based on the low methodology quality and small sample size and long studies execute time, we will not be able to obtain reliable, high-quality clinical evidence about COVID-19 treatment in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for the clinical trials of COVID-19 in China. |
3 | ep7ezoko | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Current progress in the development of a prophylactic vaccine for HIV-1 Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts' immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts. |
17 | 4el6qq3n | are there any clinical trials available for the coronavirus | Rapid review for the anti-coronavirus effect of remdesivir. The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification. |
5 | 8prn86g6 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3'-fluoro-3'-deoxythymidine triphosphate, 3'-azido-3'-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19. |
34 | hkry89ck | What are the longer-term complications of those who recover from COVID-19? | Characteristics, Treatment Outcomes and Role of Hydroxychloroquine among 522 COVID-19 hospitalized patients in Jaipur City: An Epidemio-Clinical Study. Purpose The present study was undertaken to investigate epidemiological distribution, clinical manifestation, co morbid status, treatment strategy and case fatality index of emerging COVID-19 infection at SMS Medical College Hospital, Jaipur, Rajasthan. It also evaluated efficacy of hydroxychloroquine (HCQ) in treatment of patients and risk of serious adverse outcomes in patients with COVID-19 in relation to their co morbid status. Materials and methods In an attempt to provide extensive information pertaining to epidemiological and clinical characteristics of COVID-19, the present study was undertaken on 522 patients. The patients were COVID-19 confirmed positive by genomic analysis through Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at SMS Medical College and Attached Hospitals, Jaipur. The indoor admitted patient's information inclusive of demographic profile (age, sex, nationality, residence), date of confirmation for positive COVID-19 case, travel/ exposure history, date of recovery/ death, clinical features, co morbidities and treatment plan was recorded. A serial follow-up of recovered patients to evaluate infective period of the disease was also part of the study. Results A total of 522 patients of laboratory confirmed COVID-19 test by RT-PCR at SMS Hospitals, Jaipur were assessed. Among the confirmed cases, most of patients were young adult in the age group with mean age of 35.42 years. 22.41% patients were below 20 years of age, majority of patients (58.80%) were in the age range of 21 to 50 years and only 18.79% patient population was in the age range of above 50 years. Females (39.08%) were affected less than males (60.91%) with an average sex ratio of female: male being 0.64. Out of the total analyzed patients, only 24.32% patients were symptomatic, among them fever (55.90%), cough (52.75%), sore throat (49.60%) and shortness of breath (46.45%) were the most common presenting clinical manifestations while a few patients also had symptoms of headache (26.77%), chest pain (6.29%) and other symptoms (7.87%) like pain abdomen, fatigue, joints pain, altered sensorium etc. Most of symptomatic patients belonging to older age group. An average of 40.40% patient population of above 50 years of age, were symptomatic while none of the patients below 10 years of age were symptomatic. 13.98% patients had some or the other underlying co morbid disease. The most prevalent co morbidity was hypertension (42.46%) followed by Diabetes mellitus (39.72%), Old k-chest (20.54%), COPD/ Bronchial Asthma (16.43%), Coronary artery disease (13.69%), Chronic kidney disease (13.69%) and Valvular heart disease (6.84%) distributed in co morbid patients of COVID-19. 60.27% of patient population with underlying co morbid conditions were more prone to develop symptomatology complex as compared to that observed in patients with no co morbidity (18.42%). 116 patients had recovered with effective treatment till the date of data analysis. Time of recovery was counted from the date of positive report to 1st negative report of oropharyngeal sample by RT-PCR for COVID-19 with an average recovery time of 8.15 days. 23.27% patients recovered within 5 days, while 52.58% patients took about 6-10 days, 23.27% patients took 11-15 days and remaining 0.86% took more than 16 days to recover. In the present study 15 patients had died till analysis of data, among the deceased, 73.33% were above 50 year of age with a male preponderance (66.6%). Interestingly, all deceased (100%) had presented with clinical manifestations of COVID-19 and all had underlying multiple co morbid conditions. Majority of patients had early mortality after admission to hospital with two third death account in initial three days. Asymptomatic patients (cases) treated with HCQ recovered early (average recovery time =5.4 days) compared to asymptomatic patients who did not receive any treatment (control group) and had longer recovery time (average recovery time =7.6 days). Conclusion The varied spectra of COVID-19 mostly affects young adult age group (third to fifth decades of life). Interestingly, early age group was also affected in significant proportion when compared with similar data from other countries. It was observed that male population seemed to be was more prone to getting infected. Majority of COVID-19 positive patients (nearly three-fourth) were asymptomatic (mostly in young age range) at the time of diagnosis, which poses a major challenge for health care workers. Fever, cough, sore throat and shortness of breath were major symptoms that could be detected in such COVID-19 patients. Symptomatic clinical manifestations were more common in old age population. Infectivity was higher in patients that had underlying co morbid disease, especially in patients with multiple co morbid conditions. Symptomatic presentation of COVID-19 was observed to be higher in patients with co morbid disease. Average recovery time from COVID-19 was 8 days with effective treatment. Mortality in COVID-19 was higher in old age population, male gender, symptomatic and co morbid patients as compared to other similarly matched group. Most of mortality was noted within first few days of admission, suggestive of early mortality due to the primary disease process. Treatment with HCQ had early recovery without effectively influencing the overall mortality. |
41 | rwh56zhg | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes We analyse global data for COVID-19 deaths and recoveries and show that outbreak severity displays a striking latitude relationship with a northern hemisphere bias. Transmission rates can be explained by seasonal weather conditions, but this does not account for observed variations in fatality rates. Many factors point to Vitamin D as a candidate explanation but historical controversy surrounding Vitamin D studies and the lack of a coherent framework for causal inference has hampered acceptance of this explanation despite a wealth of evidence in its favour. We analyse global COVID-19 data using Causal Inference, constructing two contrasting directed acyclic graph (DAG) models, one causal and one acausal, and set out clearly multiple predictions made by each model. We show that observed data strongly match predictions made by the causal model but largely contradict those of the acausal model. We explore historic evidence further supporting the causal model. We review biochemical mechanisms that may explain the various ways in which vitamin D acts. We detail the mechanisms by which the SARS-Cov-2 virus causes the disease and known pathways that involve Vitamin D and show how these both protect against viral infection, as well as ameliorating disease symptoms in COVID-19 and other respiratory diseases. We examine the factors that govern confidence in causal inference models and conclude that a high level of confidence in a causal beneficial role for Vitamin D is justified. |
15 | 46ecndhl | how long can the coronavirus live outside the body | Protecting Health Care Workers: Use of a Body Covering Transparent Sheet During and After Intubation of Patients With COVID-19 |
19 | r66eulqj | what type of hand sanitizer is needed to destroy Covid-19? | Masks and thermometers: Paramount measures to stop the rapid spread of SARS-CoV-2 in the United States Abstract In the United States, there is currently an exponential growth for the COVID-19 cases. The US president's coronavirus guidelines for Americans "30 Days to Slow The Spread" are necessary. To effectively curb the rapid spread of SARS-CoV-2, two more control measures masks and thermometers are strongly suggested to be included in the Guidelines. |
14 | c8byhwsj | what evidence is there related to COVID-19 super spreaders | SUPERSPREADING AS A REGULAR FACTOR OF THE COVID-19 PANDEMIC An impact of superspreading on the course of the COVID-19 epidemic is considered. A two-component model of the epidemic has been developed, in which all infected are divided in two groups. They are asymptomatic superspreaders spreading the infection and sensitive persons which can only get infection. Once infected the sensitive exhibit clear symptoms and become isolated. Taking into account both factors allows find the numbers of superspreaders and sensitive persons. It is shown, that the ratio of increment of the number of daily cases in the beginning of the epidemic and decrement at the end of the epidemic is equal to the ratio of numbers of the superspreaders and sensitive persons. In this way, on the base of data from 12 countries and territories, the share of asymptomatic among all infected persons is found to be (17 {+/-} 3)%. Specific measures to limit the epidemical incidence are proposed. The possibility of an allergic component in the disease is discussed. |
39 | ex9nh1yi | What is the mechanism of cytokine storm syndrome on the COVID-19? | The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called "cytokine storm" an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account. |
19 | y361gz5i | what type of hand sanitizer is needed to destroy Covid-19? | Is hand hygiene frequency associated with the onset of outbreaks in pediatric long-term care? BACKGROUND: Studies in adult long-term care facilities (LTCFs) have shown a correlation between hand hygiene (HH) and viral outbreak reduction, but no such studies have been conducted in pediatric LTCFs where the epidemiology of viral pathogens is different. METHODS: We compared electronically monitored facility-wide HH frequency in the weeks immediately prior to outbreaks of acute respiratory or gastrointestinal infections versus control weeks in a 137-bed pediatric LTCF from October 2012-August 2015. Control weeks were the 8-14 day (control 1) and 15-21 day (control 2) periods prior to the onset of each outbreak. RESULTS: There was no difference in HH frequency in the weeks leading up to the outbreaks versus control weeks (odds ratio [OR], 1.0; 95% confidence interval CI, 1.00-1.001 using control 1 and OR, 1.0; 95% CI, 1.00-1.001 using control 2). CONCLUSIONS: Our findings differed from those in adult LTFCs, possibly because of the greater contact between residents and staff in the pediatric setting, increased susceptibility to viral pathogens because of immunologic immaturity, or differences in the types of pathogens prevalent in each setting. Although HH may be important for limiting the number of residents infected during outbreaks, we found no association between HH frequency and subsequent outbreak onset. |
10 | r57blz6d | has social distancing had an impact on slowing the spread of COVID-19? | Wider collateral damage to children in the UK because of the social distancing measures designed to reduce the impact of COVID-19 in adults |
25 | 761ymmaf | which biomarkers predict the severe clinical course of 2019-nCOV infection? | A systematic review of the overlap of fluid biomarkers in delirium and advanced cancer-related syndromes BACKGROUND: Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. Understanding of delirium pathophysiology is largely hypothetical, with some evidence for involvement of inflammatory systems, neurotransmitter alterations and glucose metabolism. To date, there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue. This systematic review explores biomarker overlap in delirium, specific advanced cancer-related syndromes and prediction of cancer prognosis. METHODS: A systematic review (PROSPERO CRD42017068662) was conducted, using MEDLINE, PubMed, Embase, CINAHL, CENTRAL and Web of Science, to identify body fluid biomarkers in delirium, cancer prognosis and advanced cancer-related syndromes of interest. Studies were excluded if they reported delirium tremens only; did not measure delirium using a validated tool; the sample had less than 75% of participants with advanced cancer; measured tissue, genetic or animal biomarkers, or were conducted post-mortem. Articles were screened for inclusion independently by two authors, and data extraction and an in-depth quality assessment conducted by one author, and checked by two others. RESULTS: The 151 included studies were conducted in diverse settings in 32 countries between 1985 and 2017, involving 28130 participants with a mean age of 69.3 years. Seventy-one studies investigated delirium biomarkers, and 80 studies investigated biomarkers of an advanced cancer-related syndrome or cancer prognosis. Overall, 41 biomarkers were studied in relation to both delirium and either an advanced cancer-related syndrome or prognosis; and of these, 24 biomarkers were positively associated with either delirium or advanced cancer syndromes/prognosis in at least one study. The quality assessment showed large inconsistency in reporting. CONCLUSION: There is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes. Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better understanding the discrete pathophysiology of delirium in the context of co-existing illness. |
44 | r3g59wsb | How much impact do masks have on preventing the spread of the COVID-19? | On airborne transmission and control of SARS-Cov-2 The COVID-19 pandemic is creating a havoc situation across the globe that modern society has ever seen. Despite of their paramount importance, the transmission routes of SARS-Cov-2 still remain debated among various sectors. Evidences compiled here strongly suggest that the COVID-19 could be transmitted via air in inadequately ventilated environments. Existing experimental data showed that coronavirus survival was negatively impacted by ozone, high temperature and low humidity. Here, regression analysis showed that the spread of SARS-Cov-2 was reduced by increasing ambient ozone concentration level from 48.83 to 94.67 µg/m3 (p-value = 0.039) and decreasing relative humidity from 23.33 to 82.67% (p-value = 0.002) and temperature from -13.17 to 19 °C) (p-value = 0.003) observed for Chinese cities during Jan-March 2020. Besides using these environmental implications, social distancing and wearing a mask are strongly encouraged to maximize the fight against the COVID-19 airborne transmission. At no other time than now are the scientists in various disciplines around the world badly needed by the society to collectively confront this disastrous pandemic. |
3 | v8p0sbi7 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | The Eleventh Hour |
31 | 9objjgsj | How does the coronavirus differ from seasonal flu? | Symptomatology during seasonal coronavirus infections in children is associated with viral and bacterial co-detection Lower respiratory tract symptoms during seasonal coronavirus infections in children are associated with RSV co-detection and increased levels of Haemophilus and Fusobacterium species. |
37 | 3854ddb9 | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | A data-driven hypothesis on the epigenetic dysregulation of host metabolism by SARS coronaviral infection: potential implications for the SARS-CoV-2 modus operandi COVID-19, the disease caused by the novel SARS-CoV-2, a betacoronavirus structurally similar to SARS-CoV. Based on both structural and syndromic similarities with SARS-CoV, a hypothesis is formed on SARS-CoV-2 potential to affect the host's metabolism as part of its lifecycle. This hypothesis is evaluated by (a) exploratory analysis of SARS-CoV / human transcriptomic interaction data and gene set enrichment analysis (b) a confirmatory, focused review of the literature based on the findings by (a). A STRING Viruses (available search for human – SARS-CoV (NCBI taxonomy Id: 9606 vs. NCBI taxonomy Id: 694009) genomic interactions reveals ten human proteins, interacting with SARS-CoV: SGTA, FGL2, SPECC1, STAT3, PHB, BCL2L1, PPP1CA, CAV1, JUN, XPO1. Gene set enrichment analyses (GSEA) with STRING on this network revealed their role as a putative protein – protein interaction network (PPI; Enrichment p-value=0.0296) mediating, viral parasitism, interleukin as well as insulin signaling, diabetes and triglyceride catabolism. In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle. Conversely, currently there are only non-causative, observational evidence of worse outcomes for COVID-19 patients with comorbid diabetes or hyperglycemia. No study has reported on the lipid profiles of COVID-19 patients; however, lipid-targeting molecules have been proposed as agents against SARS-CoV-2. Future studies, reporting on lipid and glucose metabolism of COVID-19 patients could help elucidate the disease's seculae and aid drug design. |
3 | ofd2ipvs | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation. |
25 | h5b7mncf | which biomarkers predict the severe clinical course of 2019-nCOV infection? | Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection OBJECTIVE: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. METHODS: We included patients hospitalized at the University Hospital of Rome Tor Vergata, medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. RESULTS: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. CONCLUSIONS: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms were present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned. |
2 | 6hwedoh7 | how does the coronavirus respond to changes in the weather | Estimated Effects of Projected Climate Change on the Basic Reproductive Number of the Lyme Disease Vector Ixodes scapularis Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate. Objectives: We quantified potential effects of future climate change on the basic reproduction number (R(0)) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general. Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I. scapularis population model to hindcast recent, and project future, effects of climate warming on R(0). Modeled R(0) increases were compared with R(0) ranges for pathogens and parasites associated with variations in key ecological and epidemiological factors (obtained by literature review) to assess their epidemiological importance. Results: R(0) for I. scapularis in North America increased during the years 1971–2010 in spatio-temporal patterns consistent with observations. Increased temperatures due to projected climate change increased R(0) by factors (2–5 times in Canada and 1.5–2 times in the United States), comparable to observed ranges of R(0) for pathogens and parasites due to variations in strains, geographic locations, epidemics, host and vector densities, and control efforts. Conclusions: Climate warming may have co-driven the emergence of Lyme disease in northeastern North America, and in the future may drive substantial disease spread into new geographic regions and increase tick-borne disease risk where climate is currently suitable. Our findings highlight the potential for climate change to have profound effects on vectors and vector-borne diseases, and the need to refocus efforts to understand these effects. Citation: Ogden NH, Radojević M, Wu X, Duvvuri VR, Leighton PA, Wu J. 2014. Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis. Environ Health Perspect 122:631–638; http://dx.doi.org/10.1289/ehp.1307799 |
35 | t5wl0bih | What new public datasets are available related to COVID-19? | BOAssembler: A Bayesian Optimization Framework to Improve RNA-Seq Assembly Performance High throughput sequencing of RNA (RNA-Seq) can provide us with millions of short fragments of RNA transcripts from a sample. How to better recover the original RNA transcripts from those fragments (RNA-Seq assembly) is still a difficult task. For example, RNA-Seq assembly tools typically require hyper-parameter tuning to achieve good performance for particular datasets. This kind of tuning is usually unintuitive and time-consuming. Consequently, users often resort to default parameters, which do not guarantee consistent good performance for various datasets. Results: Here we propose BOAssembler, a framework that enables end-to-end automatic tuning of RNA-Seq assemblers, based on Bayesian Optimization principles. Experiments show this data-driven approach is effective to improve the overall assembly performance. The approach would be helpful for downstream (e.g. gene, protein, cell) analysis, and more broadly, for future bioinformatics benchmark studies. Availability: https://github.com/shunfumao/boassembler. |
41 | 1dkkwt7h | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Updated estimates of comorbidities associated with risk for COVID-19 complications based on US data We updated previous estimates (wwwnc.cdc.gov/eid/article/26/8/20-0679_article) of adults with any underlying condition increasing risk of complications from COVID-19 using recent US hospitalization data instead of mortality data from China. This substitutes obesity for cancer in the definition and increased the percentage of adults reporting more than 1 condition to 56.0% (95% CI 55.7-56.4). When controlled for all measures listed, factors increasing odds of reporting any of the underlying conditions include being male, older, African American, American Indian, household income <$25,000, < high school education, underinsurance, living in the South or Midwest (vs. West), plus the risk factors of ever smoking, sedentary lifestyle, and inadequate fruit and vegetable consumption. Population-attributable risk for the listed risk factors was 13.0%, 12.6%, and 15.0% respectively. Results have potential implications for policies based on risk-stratification of the population and for improvement of risk status through lifestyle change. National support for a health promotion campaign would be timely. |
8 | jamd5ubd | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Acute complications and mortality in hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis BACKGROUND: The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on clinically relevant outcomes in hospitalized patients with COVID-19. METHODS: MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses. RESULTS: A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies). CONCLUSIONS: Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting. TRIAL REGISTRATION: PROSPERO registration ID for this study is CRD42020177243 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243). |
12 | ivqbqdh0 | what are best practices in hospitals and at home in maintaining quarantine? | A data driven time-dependent transmission rate for tracking an epidemic: a case study of 2019-nCoV |
27 | 5m895fhj | what is known about those infected with Covid-19 but are asymptomatic? | Respiratory virus associated with surgery in children patients BACKGROUND: Viral respiratory infection (VRI) is a common contraindication to elective surgery. Asymptomatic shedding among pediatric surgery patients (PSPs) could potentially lead to progression of symptomatic diseases and cause outbreaks of respiratory diseases. The aim of this study is to investigate the incidence of infection among mild symptomatic PSP group and asymptomatic PSP group after surgical procedure. METHODS: We collected the induced sputum from enrolled 1629 children (under 18 years of age) with no respiratory symptom prior to pediatric surgery between March 2017 and February 2019. We tested 16 different respiratory virus infections in post-surgery mild symptomatic PSP group and asymptomatic PSP group using a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assay panel. We analyzed symptom data and quantitative viral load to investigate the association between viruses, symptoms and viral quantity in qRT-PCR-positive PSPs. RESULTS: Out of 1629 children enrolled, a total of 204 respiratory viruses were present in 171 (10.50%) PSPs including 47 patients with mild symptoms and 124 with no symptoms after surgery. Commonly detected viruses were human rhino/enterovirus (HRV/EV, 42.19%), parainfluenza virus 3 (PIV3, 24.48%), coronavirus (CoV NL63, OC43, HKU1, 11.46%), and respiratory syncytial virus (RSV, 9.9%). PIV3 infection with a higher viral load was frequently found in PSPs presenting with mild symptoms, progressing to pneumonia with radiographic evidence after surgery. HRV/EV were the most commonly detected pathogens in both asymptomatic and mild symptomatic PSPs. CoV (OC43, HKU1) infections with a higher viral load were mostly observed in asymptomatic PSPs progressing to alveolar or interstitial infiltration. CONCLUSIONS: Our study suggested that PIV3 is a new risk factor for VRI in PSPs. Employing a more comprehensive, sensitive and quantitative method should be considered for preoperative testing of respiratory viruses in order to guide optimal surgical timing. |
39 | 0fgquau3 | What is the mechanism of cytokine storm syndrome on the COVID-19? | Cytokine storm in COVID‐19 and parthenolide: preclinical evidence A group of patients with pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) were reported from China in December 2019. Although several antiviral drugs are widely tested, none of them has been approved as specific antiviral therapy for coronavirus disease 2019 (COVID‐19). Accumulating evidence established a hyperinflammatory states or cytokine storm in COVID‐19. Among these cytokines, IL‐6 plays a key role in cytokine storm and can predict the adverse clinical outcomes and fatality in these patients. Based on the evidence of the significant role of IL‐6 in cytokine storm, diabetes mellitus and cardiovascular diseases as principal comorbidities, it seems that anti‐cytokine therapy may be useful in patients with severe COVID‐19 to reduce mortality. Recent studies demonstrated that herbal‐derived natural products had immunosuppressive and anti‐inflammatory properties and exhibited exceptional act on mediators of inflammation. Parthenolide is the principal sesquiterpene lactones and the main biologically active constituent Tanacetum parthenium (commonly known as feverfew) which has could significantly reduce IL‐1, IL‐2, IL‐6, IL‐8, and TNF‐α production pathways established in several human cell line models in vitro and in vivo studies. Therefore, parthenolide may be one of the herbal candidates for clinical evaluation. This article is protected by copyright. All rights reserved. |
8 | aoqyx8mk | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Stochastic discrete epidemic modeling of COVID-19 transmission in the Province of Shaanxi incorporating public health intervention and case importation Before the lock-down of Wuhan/Hubei/China, on January 23rd 2020, a large number of individuals infected by COVID-19 moved from the epicenter Wuhan and the Hubei province due to the Spring Festival, resulting in an epidemic in the other provinces including the Shaanxi province. The epidemic scale in Shaanxi was comparatively small and with half of cases being imported from the epicenter. Based on the complete epidemic data including the symptom onset time and transmission chains, we calculate the control reproduction number (1.48-1.69) in Xian. We could also compute the time transition, for each imported or local case, from the latent, to infected, to hospitalized compartment, as well as the effective reproduction number. This calculation enables us to revise our early deterministic transmission model to a stochastic discrete epidemic model with case importation and parameterize it. Our model-based analyses reveal that the newly generated infections decay to zero quickly; the cumulative number of case-driven quarantined individuals via contact tracing stabilize at a manageable level, indicating that the intervention strategies implemented in the Shaanxi province have been effective. Risk analyses, important for the consideration of resumption of work, show that a large second outbreak is expected if the level of case importation remains at the same level as between January 10th and February 4th 2020. However, if the case importation decreases by 30%, 60% and 90%, the second outbreak if happening will be of small-scale assuming contact tracing and quarantine/isolation remain as effective as before. Finally, we consider the effects of intermittent inflow with a Poisson distribution on the likelihood of multiple outbreaks. We believe the developed methodology and stochastic model provide an important model framework for the evaluation of revising travel restriction rules in the consideration of resuming social-economic activities while managing the disease control with potential case importation. |
34 | vkgnwxzc | What are the longer-term complications of those who recover from COVID-19? | Estimate the incubation period of coronavirus 2019 (COVID-19) Motivation: Wuhan pneumonia is an acute infectious disease caused by the 2019 novel coronavirus (COVID-19). It is being treated as a Class A infectious disease though it was classified as Class B according to the Infectious Disease Prevention Act of China. Accurate estimation of the incubation period of the coronavirus is essential to the prevention and control. However, it remains unclear about its exact incubation period though it is believed that symptoms of COVID-19 can appear in as few as 2 days or as long as 14 or even more after exposure. The accurate incubation period calculation requires original chain-of-infection data that may not be fully available in the Wuhan regions. In this study, we aim to accurately calculate the incubation period of COVID-19 by taking advantage of the chain-of-infection data, which is well-documented and epidemiologically informative, outside the Wuhan regions. Methods: We acquired and collected officially reported COVID-19 data from 10 regions in China except for Hubei province. To achieve the accurate calculation of the incubation period, we only involved the officially confirmed cases with a clear history of exposure and time of onset. We excluded those without relevant epidemiological descriptions, working or living in Wuhan for a long time, or hard to determine the possible exposure time. We proposed a Monte Caro simulation approach to estimate the incubation of COVID-19 as well as employed nonparametric ways. We also employed manifold learning and related statistical analysis to decipher the incubation relationships between different age/gender groups. Result: The incubation period of COVID-19 did not follow general incubation distributions such as lognormal, Weibull, and Gamma distributions. We estimated that the mean and median of its incubation were 5.84 and 5.0 days via bootstrap and proposed Monte Carlo simulations. We found that the incubation periods of the groups with age>=40 years and age<40 years demonstrated a statistically significant difference. The former group had a longer incubation period and a larger variance than the latter. It further suggested that different quarantine time should be applied to the groups for their different incubation periods. Our machine learning analysis also showed that the two groups were linearly separable. incubation of COVID-19 along with previous statistical analysis. Our results further indicated that the incubation difference between males and females did not demonstrate a statistical significance. |
35 | thu861hj | What new public datasets are available related to COVID-19? | An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov) The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th(,) 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented. |
15 | kfx0qvkp | how long can the coronavirus live outside the body | Chapter 5 Host Range, Host–Virus Interactions, and Virus Transmission Summary Three intricate and intertwined biological features in the replication cycle of viruses are covered in this chapter: The range of cellular entities that support virus replication and/or virus transmission, and the various relationships viruses establish with their hosts and biological vectors. Although in its infancy, an explosion of research on virus–host interactions has already revealed surprising relationships ranging from strictly parasitic to mutualistic, and some others in between. A clearer picture is emerging as regards to our understanding of the full spectrum of these interactions, even with varying experimental approaches and differing opinions on terminology and data interpretation. |
49 | 73z243kv | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | T cell-mediated host immune defenses in the lung. Evidence has increasingly shown that the lungs are a major site of immune regulation. A robust and highly regulated immune response in the lung protects the host from pathogen infection, whereas an inefficient or deleterious response can lead to various pulmonary diseases. Many cell types, such as epithelial cells, dendritic cells, macrophages, neutrophils, eosinophils, and B and T lymphocytes, contribute to lung immunity. This review focuses on the recent advances in understanding how T lymphocytes mediate pulmonary host defenses against bacterial, viral, and fungal pathogens. |
13 | 7gl5lptp | what are the transmission routes of coronavirus? | Epidemiological analysis on a family cluster of COVID-19/ 中华流行病学杂志 Objective@#To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic.@*Methods@#Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR.@*Results@#Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020.@*Conclusions@#In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19. |
17 | 6wszpqvx | are there any clinical trials available for the coronavirus | Clinical trials for the prevention and treatment of COVID‐19: current state of play Since coronavirus disease 2019 (COVID‐19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID‐19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID‐19; treatment of hospitalised patients with moderate COVID‐19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir–ritonavir (seven trials) and remdesevir (five trials). There are many candidate drugs in pre‐clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe. |
21 | z5dy8kxf | what are the mortality rates overall and in specific populations | Interim Analysis of Pandemic Coronavirus Disease 2019 (COVID-19) and the SARS-CoV-2 virus in Latin America and the Caribbean: Morbidity, Mortality and Molecular Testing Trends in the Region Background: The relentless advance of the SARS-CoV-2 virus pandemic has resulted in a significant burden on countries, regardless of their socio-economic conditions. The virus has infected more than 2.5 million people worldwide, causing to date more than 150,000 deaths in over 210 countries. Objective: The aim of this study was to describe the trends in cases, tests and deaths related to novel coronavirus disease (COVID-19) in Latin American and Caribbean (LAC) countries. Methodology: Data were retrieved from the WHO-Coronavirus Disease (COVID-2019) situation reports and the Center for Systems Science and Engineering (CSSE) databases from Johns Hopkins University. Descriptive statistics including death rates, cumulative mortality and incidence rates, as well as testing rates per population at risk were performed. A comparison analysis among countries with [≥]50 confirmed cases was performed from February 26th, 2020 to April 8th, 2020. Results: Brazil had the greatest number of cases and deaths in the region. Panama experienced a rapid increase in the number of confirmed cases with Trinidad and Tobago, Bolivia and Honduras having the highest case fatality rates. Panama and Chile conducted more tests per million inhabitants and more tests per day per million inhabitants, followed by Uruguay and El Salvador. Dominican Republic, Bolivia, Ecuador and Brazil had the highest positive test rates. Conclusions: The COVID-19 disease pandemic caused by the SARS-CoV-2 virus has progressed rapidly in LAC countries. Some countries have been affected more severely than others, with some adopting similar disease control methods to help slow down the spread of the virus. With limited testing and other resources, social distancing is needed to help alleviate the strain on already stretched health systems. |
20 | 5f42du0b | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission. |
26 | txssq1p1 | what are the initial symptoms of Covid-19? | Novel coronavirus infection in children outside of Wuhan, China BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID‐19) has spread rapidly, but information about children with COVID‐19 is limited. METHODS: This retrospective and the single‐center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID‐19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019‐nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019‐nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground‐glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT‐PCR for 2019‐nCoV and were discharged. The median time from exposure to a negative RT‐PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis. |
45 | vlv71g68 | How has the COVID-19 pandemic impacted mental health? | Impact of COVID-19 on transportation in Lagos, Nigeria Abstract The growing number of studies on the impact of COVID-19 is often discussed in the context of developed countries, highlighting a gap in the understanding of how the pandemic is impacting developing countries. This theoretical commentary focuses on the present and long-term impact of COVID-19 on transportation in Lagos State, Nigeria. The paper recognises the effect on transportation in emerging economies, where lockdowns and restrictions on movement may be ineffective, a state with high population density, poor transportation infrastructure and a large informal economy. Adopting the 'avoid-shift-improve' framework, this paper presents practical implications for public and private sector policymakers, as they navigate this precarious time and chart a new path for individuals and Nigeria. |
9 | 1ocg0gj3 | how has COVID-19 affected Canada | Controlling SARS: a review on China's response compared with other SARS‐affected countries Objective To summarise the major control measures implemented by severe acute respiratory syndrome (SARS)‐affected countries and to compare distinctive features of the Chinese approach to other affected Asian countries and Canada. Method Literature review. Results The realisation in March 2003 that SARS was spreading led affected countries to introduce measures such as rapid dissemination of information, early case detection and isolation, tracing and quarantining of SARS contacts, traveller screening, raising public awareness of risk and institution of stricter infection control in health care settings. SARS became a notifiable disease in China in mid‐April 2003, after which introduction of efficient nationwide control measures led to containment within 2 months. Countries differed in the timeliness of implementing control measures, the mode and extent to which these were enforced and in the resources available to do so. Conclusion SARS challenged the political and public health systems of all affected countries. It demanded rapid and decisive action to be taken, yet the comparison shows how difficult this was for an unknown new disease. Guangdong reacted rapidly but this pace was not continued by China for some time, which facilitated national and international spread. Once the Chinese government changed its policy, it developed an impressive control strategy involving the public which culminated in containment. The significance of timely information was perhaps the main lesson which the SARS epidemic taught. |
26 | p119i282 | what are the initial symptoms of Covid-19? | A Two-Tube Multiplex Reverse Transcription PCR Assay for Simultaneous Detection of Sixteen Human Respiratory Virus Types/Subtypes There is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. With an intended application in provincial Centers for Diseases Control and Prevention, in this study, we present a two-tube multiplex RT-PCR assay (two-tube assay) using automatic electrophoresis to simultaneously detect sixteen common respiratory viruses. The specificity and the sensitivity of the assay were tested. The assay could detect 20–200 copies per reaction when each viral type was assayed individually, 2000 copies with 9 premixed viral targets in the multiplexed assay in tube 1, and 200 copies with 8 premixed templates in tube 2. A total of 247 specimens were used to evaluate the two-tube assay, and the results were compared with those obtained from the Luminex xTAG RVP Fast assay. The discordant results were confirmed by sequencing or by the Seeplex RV15 ACE detection kit. There were no false positives, but six false negatives occurred with the two-tube assay. In conclusion, the two-tube assay is demonstrated to have great potential for routine surveillance of respiratory virus infection in China. |
2 | mrz3s90w | how does the coronavirus respond to changes in the weather | Estimation of Time-Dependent Reproduction Numbers for Porcine Reproductive and Respiratory Syndrome across Different Regions and Production Systems of the US Porcine reproductive and respiratory syndrome (PRRS) is, arguably, the most impactful disease for the North American swine industry, due to its known considerable economic losses. The Swine Health Monitoring Project (SHMP) monitors and reports weekly new PRRS cases in 766 sow herds across the US. The time-dependent reproduction number (TD-R) is a measure of a pathogen's transmissibility. It may serve to capture and report PRRS virus (PRRSV) spread at the regional and system levels. The primary objective of the study here was to estimate the TD-R values for PRRSV using regional and system-level PRRS data, and to contrast it with commonly used metrics of disease, such as incidence estimates and space–time clusters. The second objective was to test whether the estimated TD-Rs were homogenous across four US regions. Retrospective monthly incidence data (2009–2016) were available from the SHMP. The dataset was divided into four regions based on location of participants, and demographic and environmental features, namely, South East (North Carolina), Upper Midwest East (UME, Minnesota/Iowa), Upper Midwest West (Nebraska/South Dakota), and South (Oklahoma panhandle). Generation time distributions were fit to incidence data for each region, and used to calculate the TD-Rs. The Kruskal–Wallis test was used to determine whether the median TD-Rs differed across the four areas. Furthermore, we used a space–time permutation model to assess spatial–temporal patterns for the four regions. Results showed TD-Rs were right skewed with median values close to "1" across all regions, confirming that PRRS has an overall endemic nature. Variation in the TD-R patterns was noted across regions and production systems. Statistically significant periods of PRRSV spread (TD-R > 1) were identified for all regions except UME. A minimum of three space–time clusters were detected for all regions considering the time period examined herein; and their overlap with "spreader events" identified by the TD-R method varied according to region. TD-Rs may help to measure PRRS spread to understand, in quantitative terms, disease spread, and, ultimately, support the design, implementation, and monitoring of interventions aimed at mitigating the impact of PRRSV spread in the US. |
26 | c8ntugof | what are the initial symptoms of Covid-19? | Cutaneous manifestations in COVID-19: familial cluster of urticarial rash |
39 | lodb579q | What is the mechanism of cytokine storm syndrome on the COVID-19? | Sex Hormones and Novel Corona Virus Infectious Disease (COVID-19) Abstract Given the rapid spread of the COVID-19 pandemic and its overwhelming impact on health care systems and the global economy, innovative therapeutic strategies are urgently needed. The proposed primary culprit of COVID-19 is the intense inflammatory response—an augmented immune response and cytokine storm—severely damaging the lung tissue and rendering some patients' conditions severe enough to require assisted ventilation. Sex differences in the response to inflammation have been documented and can be attributed, at least in part, to sex steroid hormones. Moreover, age associated decreases in sex steroid hormones, namely estrogen and testosterone, may mediate pro-inflammatory increases in older adults that could increase their risk for COVID-19 adverse outcomes. Sex hormones can mitigate the inflammation response and might provide promising therapeutic potential for COVID-19 patients. In this article, we explore the possible anti-inflammatory effects of estrogen and testosterone and the anabolic effect of testosterone, with particular attention to the potential therapeutic role of hormone replacement therapy (HRT) in older men and women with COVID-19. |
23 | p5ecpcll | what kinds of complications related to COVID-19 are associated with hypertension? | Analysis on the Clinical Characteristics of 36 Cases of Novel Coronavirus Pneumonia in Kunming Objective: To analyze the clinical characteristics of patients with novel coronavirus pneumonia in Kunming City, and to study the correlation between nutritional status and immune function. Methods: Clinical data of 36 patients with novel coronavirus pneumonia in isolation area of Kunming Third People's Hospital from January 31 to February 15, 2020 were collected, and the basic situation, clinical characteristics, laboratory examination and CT imaging characteristics were analyzed. Serum albumin (ALB), prealbumin (PAB), hypersensitive c-reactive protein (hs-crp), CD3T cells, CD4T cells, CD8T cells and normal control group were analyzed. A simple linear regression analysis of the relationship between proalbumin and T cell subpopulation counts in the blood of patients. Results: (1) The patients with new coronavirus pneumonia in Kunming were mainly of common type. (2) 50% of the patients' first symptoms were fever and cough; (3) The total number of white blood cells in peripheral blood was normal or decreased in 23 cases (79%), and the lymphocyte count decreased in 5 cases (13.89%), without anemia. Hypersensitive c-reactive protein increased in 19 (52.78%) cases, and procalcitonin increased in 1 case. Albumin decreased in 5 cases (13.89%), proalbumin decreased in 15 cases (41.67%), alanine transaminase increased slightly in 4 cases (11.11%), alanine transaminase increased slightly in 4 cases (11.11%), total bilirubin increased slightly in 11 cases (30.56%), and renal function and blood coagulation were normal. Absolute value of CD3+T cells is with a decrease in 21 cases (58.3%), CD4+T in 28 cases (77.8%), CD8+T in 17 cases (47.2%), and CD4+/ CD8+ inverse in 6 cases (16.7%). (4) The prealbumin, CD3 T cells, CD4 T cells and CD8 T cells in the new coronavirus pneumonia group were significantly lower than those in the normal control group, and the hypersensitive c-reactive protein was higher than that in the normal control group. (5) The levels of PAB in the serum of the patients were linearly correlated with hs-crp, CD3 T cells, CD4 T cells and CD8 T cells, and the correlation coefficients were -0.474, 0.558, 0.467 and 0.613, respectively, showing statistical differences. Conclusion: The clinical characteristics of the novel coronavirus pneumonia in Kunming are different from those in Wuhan. The changes of serum proalbumin and T cell subsets are relatively obvious. Changes in serum proalbumin may contribute to the early warning of novel coronavirus pneumonia. The nutritional status of patients with common and mild pneumonia should be considered. |
20 | 3xpu1x9h | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Incidence, risk factors and clinical outcomes of acute kidney injury associated with scrub typhus: a retrospective study of 510 consecutive patients in South Korea (2001–2013) OBJECTIVES: Renal involvement in scrub typhus ranges from simple urinary abnormalities to acute kidney injury (AKI) leading to death. This study evaluated the incidence, predictors and prognosis of AKI associated with scrub typhus according to the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. METHODS: We retrospectively evaluated the medical records of patients diagnosed with scrub typhus from January 2001 to November 2013 in Gyeongsang National University Hospital. RESULTS: During the study period, 510 patients were diagnosed with scrub typhus and the incidence of AKI was 35.9%. There were 132 (25.9%) patients at risk, 37 (7.3%) with injury and 14 (2.7%) with failure. In comparison with the non-AKI group, the AKI group was older (73.9 vs 63.4 years, p<0.001) and had more comorbidities such as hypertension, diabetes mellitus and chronic kidney disease (CKD). AKI frequently occurs in hypertensive patients taking angiotensin receptor blockers or ACE inhibitors (p=0.002), and in patients with diabetes with higher glycated haemoglobin levels (p=0.033). Haematuria and proteinuria were more frequent in the AKI group. There was no relationship between the severity of proteinuria and occurrence of AKI. Intensive care unit admission and death were more frequent in the AKI group. The renal function of most patients with AKI recovered without sequelae, except for 1 patient who had underlying CKD. Multivariate analysis showed that age, presence of CKD, serum albumin level and time to hospital presentation after symptom onset were independent predictors of AKI in patients with scrub typhus. CONCLUSIONS: Our current results suggest that the presence of underlying CKD, older age, lower serum albumin level and time to hospital presentation after symptom onset were important risk factors to determine occurrence of AKI. Whether earlier diagnosis and treatment in patients with the above risk factors reduce the incidence and severity of AKI deserves to be investigated. |
21 | ejg393zs | what are the mortality rates overall and in specific populations | Novel Coronavirus Disease 2019 (COVID-19): An Emerging Infectious Disease in the 21st Century Background: At the beginning of the New Year 2020, China alerted the world health organization (WHO) to a cluster of unusual pneumonia cases in Wuhan After extensive speculation, eventually a new species of coronavirus introduced as the causative pathogen of the disease Coronavirus disease 2019 (COVID-19) is a name for the disease, and the virus that causes it is known SARS-CoV-2 The very rapid spread of the COVID-19 in China and in many other countries has caused fear among people across the world The novel coronavirus outbreak declared a Public Health Emergency of International Concern on 30 January 2020 Materials and Methods: Several databases such as PubMed, Scopus, Google scholar, and BioRxiv were searched for publications reporting on the novel coronavirus up to 29 February 2020 Literature searches were performed using keywords including "Coronavirus 2019", "2019-nCoV", "COVID-19", and "SARS-CoV-2" Moreover, websites such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) were searched to retrieve updated data and statistics regarding the novel coronavirus We extracted data on the epidemiology, pathogenesis, virology, clinical manifestations, transmission routes, diagnosis, treatment, and prevention measures Results: From the 1416 articles identified in the initial search, 53 were remained after title and abstract screening After full-text review, 37 articles were eligible to include in our study Incubation period for COVID-19 is between 2-10 days, according to the World Health Organization (WHO) The case fatality rate in patients infected with SARC-CoV-2 is 4 3%, and the results indicate that the mortality is higher in elderly individuals and patients with chronic conditions including patients with coronary artery disease, diabetes, chronic pulmonary disease, and hypertension The mortality rate in healthy subjects is less than 1% Conclusion: The outbreak caused by the novel coronavirus is larger than the previous human coronaviruses, showing that the SARS-CoV-2 is an extremely contagious virus However, the mortality rate of COVID-19 is lower than that of other coronaviruses diseases such as SARS or MERS and other viruses like HIV and Ebola Currently, due to the lack of an effective treatment and vaccine, the best way to deal with the COVID-19 disease is to prevent transmission and spread of the virus and to execute personal protective measures |
8 | 4zk4sj2d | how has lack of testing availability led to underreporting of true incidence of Covid-19? | How will country-based mitigation measures influence the course of the COVID-19 epidemic? |
17 | k1eq4l3d | are there any clinical trials available for the coronavirus | Characteristics of registered clinical trials assessing treatments for COVID-19: a cross-sectional analysis OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has prompted many initiatives to identify safe and efficacious treatments, yet little is known regarding where early efforts have focused. We aimed to characterise registered clinical trials assessing drugs or plasma treatments for COVID-19. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of clinical trials for the treatment of COVID-19 that were registered in the USA or in countries contributing to the WHO's International Clinical Trials Registry Platform. Relevant trial entries of drugs or plasma were downloaded on 26 March 2020, deduplicated, verified with reviews of major medical journals and WHO websites and independently analysed by two reviewers. MAIN OUTCOMES: Trial intervention, sponsorship, critical design elements and specified outcomes RESULTS: Overall, 201 clinical trials were registered for testing the therapeutic benefits of 92 drugs or plasma, including 64 in monotherapy and 28 different combinations. Only eight (8.7%) products or combinations involved new molecular entities. The other test therapies had a wide range of prior medical uses, including as antivirals, antimalarials, immunosuppressants and oncology treatments. In 152 trials (75.7%), patients were randomised to treatment or comparator, including 55 trials with some form of blinding and 97 open-label studies. The 49 (24.4%) of trials without a randomised design included 29 single armed studies and 20 trials with some comparison group. Most trial designs featured multiple endpoints. Clinical endpoints were identified in 134 (66.7%) of trials and included COVID-19 symptoms, death, recovery, required intensive care and hospital discharge. Clinical scales were being used in 33 (16.4%) trials, most often measures of oxygenation and critical illness. Surrogate endpoints or biomarkers were studied in 88 (42.3%) of trials, primarily assays of viral load. Although the trials were initiated in more than 17 countries or regions, 100 (49.8%) were registered in China and 78 (37.8%) in the USA. Registered trials increased rapidly, with the number of registered trials doubling from 1 March to 26 March 2020. CONCLUSIONS: While accelerating morbidity and mortality from the COVID-19 pandemic has been paralleled by early and rapid clinical investigation, many trials lack features to optimise their scientific value. Global coordination and increased funding of high-quality research may help to maximise scientific progress in rapidly discovering safe and effective treatments. |
50 | ywbyflas | what is known about an mRNA vaccine for the SARS-CoV-2 virus? | The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00428-020-02881-x) contains supplementary material, which is available to authorized users. |
6 | p5jtwb3l | what types of rapid testing for Covid-19 have been developed? | Electrochemical Molecular Analysis Without Nucleic Acid Amplification Electrochemical biosensors have revolutionized glucose monitoring but have not yet fulfilled their promise of a low cost, direct detection replacement for genetic amplification tests such as PCR [K. Kerman, M. Kobayashi, E. Tamiya, Recent trends in electro-chemical DNA biosensor technology, Meas. Sci. Technol. 15 (2004) R1-R11; A. Chaubey, B.D. Malhotra, Mediated biosensors. Biosens. Bioelectron. 17 (6-7) (2002) 441-456]. It has been anticipated that the integration of nanoscale chemical structures such as self-assembled monolayers with electrochemical biosensors would increase sensitivity by decreasing inherent system noise. We have designed a novel biosensing approach incorporating such integration and achieved rapid, ultra-low concentration sensitivities without target amplification. Raw samples are mixed with lysis buffer to allow hybridization of nucleic acid targets with anchor and signal probes before immobilizing a signaling enzyme proximate to the biosensor surface. A bias potential is subsequently applied and the secondary byproduct of a cyclic peroxidase reaction measured. Further studies have demonstrated the application of our approach in protein, clinical chemistry, and ionic assays. |
17 | pdc3bv33 | are there any clinical trials available for the coronavirus | Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94 % in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when. |
24 | kiq7h68a | what kinds of complications related to COVID-19 are associated with diabetes | Maternal postnatal health during the COVID-19 pandemic: vigilance is needed |
5 | 2hv5ohsf | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | SARS-CoV-2 Seroconversion in Humans: A Detailed Protocol for a Serological Assay, Antigen Production, and Test Setup In late 2019, cases of atypical pneumonia were detected in China. The etiological agent was quickly identified as a betacoronavirus (named SARS-CoV-2), which has since caused a pandemic. Several methods allowing for the specific detection of viral nucleic acids have been established, but these only allow detection of the virus during a short period of time, generally during acute infection. Serological assays are urgently needed to conduct serosurveys, to understand the antibody responses mounted in response to the virus, and to identify individuals who are potentially immune to re-infection. Here we describe a detailed protocol for expression of antigens derived from the spike protein of SARS-CoV-2 that can serve as a substrate for immunological assays, as well as a two-stage serological enzyme-linked immunosorbent assay (ELISA). These assays can be used for research studies and for testing in clinical laboratories. © 2020 The Authors. Basic Protocol 1: Mammalian cell transfection and protein purification Basic Protocol 2: A two-stage ELISA for high-throughput screening of human serum samples for antibodies binding to the spike protein of SARS-CoV-2. |
5 | gwm36n75 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Docking study of Chloroquine and Hydroxychloroquine interaction with SARS-CoV-2 spike glycoprotein-An in silico insight into the comparative efficacy of repurposing antiviral drugs. Recent outbreak of novel Coronavirus disease (Covid-19) pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor. Therefore, it is the main target of neutralizing antibodies upon infection and there is always a quest to inhibit the S-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for Covid-19 is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the S-protein of SARS-CoV-2. With the help of various computational methods, we have re-explored the potential role of both of these antiviral drugs for the treatment of Covid-19 patients by comparing the efficacy of both of the drugs to bind to S-protein at its host receptor region. In our research Hydroxychloroquine exhibited potential inhibitory effectsof S-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with Covid-19. Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching Covid-19 to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with Covid-19. We further hypothesize that the comparative S-protein-drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine. |
33 | i3xzlb4l | What vaccine candidates are being tested for Covid-19? | Charts and Tables |
4 | lhd0jn0z | what causes death from Covid-19? | Two mechanisms for accelerated diffusion of COVID-19 outbreaks in regions with high intensity of population and polluting industrialization: the air pollution-to-human and human-to-human transmission dynamics What is COVID-19? Coronavirus disease 2019 (COVID-19) is viral infection that generates a severe acute respiratory syndrome with serious pneumonia that may result in progressive respiratory failure and death. What are the goals of this investigation? This study explains the geo-environmental determinants of the accelerated diffusion of COVID-19 in Italy that is generating a high level of deaths and suggests general lessons learned for a strategy to cope with future epidemics similar to COVID-19 to reduce viral infectivity and negative impacts in economic systems and society. What are the results of this study? The main results are: o The accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution. o Hinterland cities have average days of exceeding the limits set for PM10 (particulate matter 10 micrometers or less in diameter) equal to 80 days, and an average number of infected more than 2,000 individuals as of April 1st, 2020, coastal cities have days of exceeding the limits set for PM10 equal to 60 days and have about 700 infected in average. o Cities that average number of 125 days exceeding the limits set for PM10, last year, they have an average number of infected individual higher than 3,200 units, whereas cities having less than 100 days (average number of 48 days) exceeding the limits set for PM10, they have an average number of about 900 infected individuals. o The results reveal that accelerated transmission dynamics of COVID-19 in specific environments is due to two mechanisms given by: air pollution-to-human transmission and human-to-human transmission; in particular, the mechanisms of air pollution-to-human transmission play a critical role rather than human-to-human transmission. o The finding here suggests that to minimize future epidemic similar to COVID-19, the max number of days per year in which cities can exceed the limits set for PM10 or for ozone, considering their meteorological condition, is less than 50 days. After this critical threshold, the analytical output here suggests that environmental inconsistencies because of the combination between air pollution and meteorological conditions (with high moisture%, low wind speed and fog) trigger a take-off of viral infectivity (accelerated epidemic diffusion) with damages for health of population, economy and society. What is a socioeconomic strategy to prevent future epidemics similar to COVID-19? Considering the complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity, lessons learned for COVID-19 have to be applied for a proactive socioeconomic strategy to cope with future epidemics, especially an environmental policy based on reduction of air pollution mainly in hinterland zones of countries, having low wind speed, high percentage of moisture and fog that create an environment that can damage immune system of people and foster a fast transmission of viral infectivity similar to the COVID-19. This study must conclude that a strategy to prevent future epidemics similar to COVID 19 has also to be designed in environmental and sustainability science and not only in terms of biology. |
48 | 8ynk9k8r | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | Global lessons and Potential strategies in combating COVID-19 pandemic in Ethiopia:Systematic Review Background: Coronavirus disease 2019 (COVID-19) is a rapidly emerging disease that has been classified a pandemic by the World Health Organization (WHO). In the absence of treatment for this virus, there is an urgent need to find alternative public health strategies to control the spread. Here, we have conducted an online search for all relevant public health interventions for COVID-19. We then characterize and summarize the global COVID-19 pandemic situation and recommend potential mitigation strategies in the context of Ethiopia. Methods: Initial search of Pub Med central and Google scholar was undertaken followed by analysis of the text words; COVID-19,SARS-CoV-2, Global lessons and Pandemic; A second search using all identified keywords including COVID-19, Epidemiology, Sociocultural, Ethiopia; thirdly, the reference list of all identified reports and articles were searched. Accordingly, of the 1,402 articles, 39 were included in the analysis for this review. Result: Countries COVID-19 mitigation strategies widely varied. The most common global COVID-19 mitigation strategies include; whole of government approach including individual, community and environmental measures, detecting and isolating cases, contact tracing and quarantine, social and physical distancing measures including for mass gatherings and international travel measures. Models revealed that, social and physical distancing alone could prevent the pandemic from 60-95%, if timely and effectively implemented. Moreover, detecting and isolation of cases were found to be crucial while access to testing was found to the global challenge. Individual measures including proper hand washing were also reported to be effective measures in preventing the pandemic. Asymptomatic cases of COVID-19 ranged from 25% to 80% and as a result, countries are revising the case definition for early detection of mild symptomatic cases of COVID-19 with inclusion of Chills, Muscle pain and new loss of taste or smell in addition to Cough, Shortness of breath, Fever and Sore throat. Global reports also revealed that the incubation period of COVID-19 could go to 24 days. Ethiopia is also unique in the aspects of sociocultural prospects while more than 99.3% of the population has a religion. Moreover, 69% of the population is under the age of 29 years old and the health policy in the country focused on prevention and primary health care. All these could be potential entries and opportunities to combat COVID-19 pandemic in the context of Ethiopia. Conclusion: While recommendations may change depending on the level of outbreak, we conclude that in Most countries have benefited from early interventions and in setups like Africa including Ethiopia where health system capability is limited, community engagement supported by local evidence with strict implementation of social and physical distancing measures is mandatory. Active involvement of religious Institutions and mobilizing youth could be entry to increase public awareness in mitigating COVID-19. Community level case detection could enhance early identification of cases which could be implemented through the health extension program. Isolation and quarantine beyond 14 days could help identify long term carriers of COVID-19. Validation and use of rapid test kits could be vital to increase access for testing. Revision of case definitions for COVID-19 could be important for early detection and identification of mild symptomatic cases. |
9 | jn5hwrny | how has COVID-19 affected Canada | Intensive Care Unit Preparedness During Pandemics and Other Biological Threats In the twenty-first century, severe acute respiratory syndrome (SARS), 2009 A(H1N1) influenza, and Ebola have all placed strains on critical care systems. In addition to the increased patient needs common to many disasters, epidemics may further degrade ICU capability when staff members fall ill, including in the course of direct patient care. In a large-scale pandemic, shortages of equipment and medications can further limit an ICU's ability to provide the normal standard of care. Hospital preparedness for epidemics must include strategies to maintain staff safety, secure adequate supplies, and have plans for triage and prioritization of care when necessary. |
38 | qu2f56p2 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Clinical Course of COVID‐19 in a Liver Transplant Recipient on Hemodialysis and Response to Tocilizumab Therapy: A Case Report The novel coronavirus disease 2019 (COVID‐19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID‐19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID‐19 pneumonia, and despite completing a 5‐day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off‐label, single‐dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID‐19. Future investigation of the effects of immunomodulators among transplant recipients with COVID‐19 infection will be important. |
16 | 45wz57ic | how long does coronavirus remain stable on surfaces? | Biosecurity for neonatal gastrointestinal diseases Infectious diarrhea is an important cause of neonatal calf morbidity and mortality that results in significant economic losses in the beef and dairy industries. Although numerous risk factors related to the occurrence of neonatal diarrhea have been identified, they can all be categorized into those that are related to the calf, the pathogens involved, or the environment of the calf. The immune status of calves, specifically the level of passively acquired immunity through colostrum, is the major risk factor related to the calf and the occurrence of diarrhea. Although numerous pathogens have been implicated in the occurrence of neonatal diarrhea, only a relatively limited number are commonly involved. Most should be viewed as secondary opportunists rather than primary pathogens, because none are extraordinarily virulent, and with the exception of Salmonella spp., most are present within the gastrointestinal tract of many healthy, mature cattle. Important risk factors related to pathogens involved in neonatal calf diarrhea involve the size of the inoculum and the occurrence of multiple infections. Finally, when considering the environment and housing conditions in which beef and dairy calves may reside, it is clear that tremendous variations exist. Despite these variations, the risk factors associated with the environment of the calf are also those that are the most amenable to the implementation of general environmental control and monitoring strategies as well as specific biosecurity measures. |
19 | sfa9d1ux | what type of hand sanitizer is needed to destroy Covid-19? | Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%‐72%) in the in‐flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5‐121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%‐23%), 29% (95% CI: 27%‐31%), and 50% (95% CI: 48%‐53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%‐87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2‐77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes. |
24 | b9fxrt0z | what kinds of complications related to COVID-19 are associated with diabetes | COVID-19 in patients with diabetes: risk factors that increase morbidity |
38 | 0lsniwyv | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members. |
20 | 4hxzdmkx | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | ACE2: from vasopeptidase to SARS virus receptor Abstract The zinc metallopeptidase angiotensin-converting enzyme 2 (ACE2) is the only known human homologue of the key regulator of blood pressure angiotensin-converting enzyme (ACE). Since its discovery in 2000, ACE2 has been implicated in heart function, hypertension and diabetes, with its effects being mediated, in part, through its ability to convert angiotensin II to angiotensin-(1–7). Unexpectedly, ACE2 also serves as the cellular entry point for the severe acute respiratory syndrome (SARS) virus and the enzyme is therefore a prime target for pharmacological intervention on several disease fronts. |
19 | nf3rdty6 | what type of hand sanitizer is needed to destroy Covid-19? | Mutations across murine hepatitis virus nsp4 alter virus fitness and membrane modifications. UNLABELLED A common feature of infection by positive-sense RNA virus is the modification of host cell cytoplasmic membranes that serve as sites of viral RNA synthesis. Coronaviruses induce double-membrane vesicles (DMVs), but the role of DMVs in replication and virus fitness remains unclear. Coronaviruses encode 16 nonstructural proteins (nsps), three of which, nsp3, nsp4, and nsp6, are necessary and sufficient for DMV formation. It has been shown previously that mutations in murine hepatitis virus (MHV) nsp4 loop 1 that alter nsp4 glycosylation are associated with disrupted DMV formation and result in changes in virus replication and RNA synthesis. However, it is not known whether DMV morphology or another function of nsp4 glycosylation is responsible for effects on virus replication. In this study, we tested whether mutations across nsp4, both alone and in combination with mutations that abolish nsp4 glycosylation, affected DMV formation, replication, and fitness. Residues in nsp4 distinct from glycosylation sites, particularly in the endoplasmic reticulum (ER) luminal loop 1, independently disrupted both the number and morphology of DMVs and exacerbated DMV changes associated with loss of glycosylation. Mutations that altered DMV morphology but not glycosylation did not affect virus fitness while viruses lacking nsp4 glycosylation exhibited a loss in fitness. The results support the hypothesis that DMV morphology and numbers are not key determinants of virus fitness. The results also suggest that nsp4 glycosylation serves roles in replication in addition to the organization and stability of MHV-induced double-membrane vesicles. IMPORTANCE All positive-sense RNA viruses modify host cytoplasmic membranes for viral replication complex formation. Thus, defining the mechanisms of virus-induced membrane modifications is essential for both understanding virus replication and development of novel approaches to virus inhibition. Coronavirus-induced membrane changes include double-membrane vesicles (DMVs) and convoluted membranes. Three viral nonstructural proteins (nsps), nsp3, nsp4, and nsp6, are known to be required for DMV formation. It is unknown how these proteins induce membrane modification or which regions of the proteins are involved in DMV formation and stability. In this study, we show that mutations across nsp4 delay virus replication and disrupt DMV formation and that loss of nsp4 glycosylation is associated with a substantial fitness cost. These results support a critical role for nsp4 in DMV formation and virus fitness. |
41 | o72ls2my | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | The dynamics of Covid-19: weather, demographics and infection timeline We study the effects of three types of variables on the early pace of spread of Covid-19: weather variables, temperature and absolute humidity; population density; the timeline of Covid-19 infection, as outbreak of disease occurs in different dates for different regions. The regions considered were all 50 U.S. states and 110 countries (those which had enough data available by April 10th. We looked for associations between the above variables and an estimate of the growth rate of cases, the exponential coefficient, computed using data for 10 days starting when state/country reached 100 confirmed cases. The results for U.S. states indicate that one cannot expect that higher temperatures and higher levels of absolute humidity would translate into slower pace of Covid-19 infection rate, at least in the ranges of those variables during the months of February and March of 2020 (-2.4 to 24C and 2.3 to 15g/m3). In fact, the opposite is true: the higher the temperature and the absolute humidity, the faster the Covid-19 has expanded in the U.S. states, in the early stages of the outbreak. Secondly, using the highest county population density for each state, there is strong positive association between population density and (early) faster spread of Covid-19. Finally, there is strong negative association between the date when a state reached 100 accumulated cases and the speed of Covid-10 outbreak (the later, the lower the estimate of growth rate). When these variables are considered together, only population density and the timeline variable show statistical significance. We also develop the basic models for the collection of countries, without the demographic variable. Despite the evidence, in that case, that warmer and more humid countries have shown lower rates of Covid-19 expansion, the weather variables lose statistical significance when the timeline variable is added. |
28 | 4egbk4yz | what evidence is there for the value of hydroxychloroquine in treating Covid-19? | Development of a Novel, Genome Subtraction-Derived, SARS-CoV-2-Specific COVID-19-nsp2 Real-Time RT-PCR Assay and Its Evaluation Using Clinical Specimens The pandemic novel coronavirus infection, Coronavirus Disease 2019 (COVID-19), has affected at least 190 countries or territories, with 465,915 confirmed cases and 21,031 deaths. In a containment-based strategy, rapid, sensitive and specific testing is important in epidemiological control and clinical management. Using 96 SARS-CoV-2 and 104 non-SARS-CoV-2 coronavirus genomes and our in-house program, GolayMetaMiner, four specific regions longer than 50 nucleotides in the SARS-CoV-2 genome were identified. Primers were designed to target the longest and previously untargeted nsp2 region and optimized as a probe-free real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. The new COVID-19-nsp2 assay had a limit of detection (LOD) of 1.8 TCID(50)/mL and did not amplify other human-pathogenic coronaviruses and respiratory viruses. Assay reproducibility in terms of cycle threshold (Cp) values was satisfactory, with the total imprecision (% CV) values well below 5%. Evaluation of the new assay using 59 clinical specimens from 14 confirmed cases showed 100% concordance with our previously developed COVID-19-RdRp/Hel reference assay. A rapid, sensitive, SARS-CoV-2-specific real-time RT-PCR assay, COVID-19-nsp2, was developed. |
8 | hfkzu18p | how has lack of testing availability led to underreporting of true incidence of Covid-19? | SARS-CoV-2 and COVID-19: The most important research questions Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis. |
34 | 2fx0w30u | What are the longer-term complications of those who recover from COVID-19? | Treatable traits and therapeutic targets: Goals for systems biology in infectious disease Abstract Among the many medical applications of systems biology, we contend that infectious disease is one of the most important and tractable targets. We take the view that the complexity of the immune system is an inevitable consequence of its evolution, and this complexity has frustrated reductionist efforts to develop host-directed therapies for infection. However, since hosts vary widely in susceptibility and tolerance to infection, host-directed therapies are likely to be effective, by altering the biology of a susceptible host to induce a response more similar to a host who survives. Such therapies should exert minimal selection pressure on organisms, thus greatly decreasing the probability of pathogen resistance developing. A systems medicine approach to infection has the potential to provide new solutions to old problems: to identify host traits that are potentially amenable to therapeutic intervention, and the host immune factors that could be targeted by host-directed therapies. Furthermore, undiscovered sub-groups with different responses to treatment are almost certain to exist among patients presenting with life-threatening infection, since this population is markedly clinically heterogeneous. A major driving force behind high-throughput clinical phenotyping studies is the aspiration that these subgroups, hitherto opaque to observation, may be observed in the data generated by new technologies. Subgroups of patients are unlikely to be static – serial clinical and biological phenotyping may reveal different trajectories through the pathophysiology of disease, in which different therapeutic approaches are required. We suggest there are two major goals for systems biology in infection medicine: (1) to identify subgroups of patients that share treatable features; and, (2) to integrate high-throughput data from clinical and in vitro sources in order to predict tractable therapeutic targets with the potential to alter disease trajectories for individual patients. |
23 | 8jhwamfv | what kinds of complications related to COVID-19 are associated with hypertension? | Calcium channel blocker amlodipine besylate is associated with reduced case fatality rate of COVID-19 patients with hypertension The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to more than 100 countries posing as a serious threat to the public health on a global scale. Patients with comorbidity such as hypertension suffer more severe infection with elevated case fatality rate. Development of effective anti-viral drug is in urgent need to treat COVID-19 patients. Here we report that calcium channel blockers (CCBs), a type of anti-hypertension drugs that are widely used in the clinics, can significantly inhibit the post-entry replication events of SARS-CoV-2 in vitro. Comparison with two other major types of anti-hypertension drugs, the angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), showed that only CCBs display significant anti-SARS-CoV-2 efficacy. Combined treatment with chloroquine and CCBs significantly enhanced the anti-SARS-CoV-2 efficacy. Retrospective clinical investigation of COVID-19 patients revealed that the CCB amlodipine besylate administration distinctly reduced the case fatality rate of patients with hypertension. Results from this study suggest that CCB administration for COVID-19 patients with hypertension as the comorbidity might improve the disease outcome. |
30 | brnm3m4g | is remdesivir an effective treatment for COVID-19 | Author index (vol. 15) |
32 | zdv0ilti | Does SARS-CoV-2 have any subtypes, and if so what are they? | COVID-19: An Update on the Epidemiological, Genomic Origin, Phylogenetic study, India centric to Worldwide current status The pandemic spread of novel coronavirus, (SARS-CoV-2) causing CoronaVirus Infectious Diseases (COVID-19) emerged into a global threat for human life causing serious death rates and economic crunch all over the globe. As on April 17, 2020 at 2:00am CEST, there include a total of 2,034,802 confirmed cases for Corona and 1,35,163 deaths worldwide have been reported which includes 212 countries, areas or territories reported by World Health Organization (WHO), in which USA tops 6,32,781 confirmed cases (28,221 deaths) followed by Italy 1,65,155 (21,647 deaths), Spain 1,77,633 (18,579 deaths) and China 84,149 (4,642 deaths). This study aims to compare the genomic nature of SARS-CoV-2 genome reported from Wuhan, China with two Indian isolate genome reported by ICMR-NIV, India. Further Phylogenetic studies performed with coronavirus infecting non-human species like Bats, Duck, and sparrow were compared with Indian and other country whole genome sequences of SARS-CoV2 using MegaX and traced out the association between the human coronavirus with the other species viral genome. In addition, epidemiological reports on COVID-19 among Worldwide and India centric data were compared between April 7, 2020 to April 17, 2020 global data and the number of active cases were increased dramatically in this 10 days period studied, highlighted in the current study. |
16 | ruk46455 | how long does coronavirus remain stable on surfaces? | Potential Fecal Transmission of SARS-CoV-2: Current Evidence and Implications for Public Health Abstract Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 affected countries. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally-mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective. |
49 | z5q82rmp | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development. |
5 | xxdrjngv | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development Abstract The pandemic spread of a novel coronavirus – SARS coronavirus-2 (SARS-CoV-2) as a cause of acute respiratory illness, named Covid-19, is placing the healthcare systems of many countries under unprecedented stress. Global economies are also spiraling towards a recession in fear of this new life-threatening disease. Vaccines that prevent SARS-CoV-2 infection and therapeutics that reduces the risk of severe Covid-19 are thus urgently needed. A rapid method to derive antiviral treatment for Covid-19 is the use of convalescent plasma derived hyperimmune globulin. However, both hyperimmune globulin and vaccine development face a common hurdle – the risk of antibody-mediated disease enhancement. The goal of this review is to examine the body of evidence supporting the hypothesis of immune enhancement that could be pertinent to Covid-19. We also discuss how this risk could be mitigated so that both hyperimmune globulin and vaccines could be rapidly translated to overcome the current global health crisis. |
15 | alo15byi | how long can the coronavirus live outside the body | Recommendations for the prevention of transmission of SARS during GI endoscopy |
37 | y2461fhh | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | On the crucial role of multilingual biomedical databases on epidemic events (SARS-CoV-2 analysis) |
1 | 9edp04ud | what is the origin of COVID-19 | Analysis and Prediction of False Negative Results for SARS-CoV-2 Detection with Pharyngeal Swab Specimen in COVID-19 Patients: A Retrospective Study Background: False negative results of SARS-CoV-2 nucleic acid detection pose threats to COVID-19 patients and medical workers alike. Objective: To develop multivariate models to determine clinical characteristics that contribute to false negative results of SARS-CoV-2 nucleic acid detection, and use them to predict false negative results as well as time windows for testing positive. Design: Retrospective Cohort Study (Ethics number of Tongji Hospital: No. IRBID: TJ-20200320) Setting: A database of outpatients in Tongji Hospital (University Hospital) from 15 January 2020 to 19 February 2020. Patients: 1,324 outpatients with COVID-19 Measurements: Clinical information on CT imaging reports, blood routine tests, and clinic symptoms were collected. A multivariate logistic regression was used to explain and predict false negative testing results of SARS-CoV-2 detection. A multivariate accelerated failure model was used to analyze and predict delayed time windows for testing positive. Results: Of the 1,324 outpatients who diagnosed of COVID-19, 633 patients tested positive in their first SARS-CoV-2 nucleic acid test (47.8%), with a mean age of 51 years (SD=14.9); the rest, which had a mean age of 47 years (SD=15.4), tested negative in the first test. Ground glass opacity in a CT imaging report was associated with a lower chance of false negatives (aOR, 0.56), and reduced the length of time window for testing positive by 26%. Consolidation was associated with a higher chance of false negatives (aOR, 1.57), and extended the length of time window for testing positive by 44%. In blood routine tests, basophils (aOR, 1.28) and eosinophils (aOR, 1.29) were associated with a higher chance of false negatives, and were found to extend the time window for testing positive by 23% and 41%, respectively. Age and gender also affected the significantly. Limitation: Data were generated in a large single-center study. Conclusion: Testing outcome and positive window of SARS-CoV-2 detection for COVID-19 patients were associated with CT imaging results, blood routine tests, and clinical symptoms. Taking into account relevant information in CT imaging reports, blood routine tests, and clinical symptoms helped reduce a false negative testing outcome. The predictive AFT model, what we believe to be one of the first statistical models for predicting time window of SARS-CoV-2 detection, could help clinicians improve the accuracy and efficiency of the diagnosis, and hence, optimizes the timing of nucleic acid detection and alleviates the shortage of nucleic acid detection kits around the world. Primary Funding Source: None. |
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