\ BIP! Finder for COVID-19 - Impact-based ranking

BIP! Finder for COVID-19

This version of BIP! Finder aims to ease the exploration of COVID-19-related literature by enabling ranking articles based on various impact metrics.

Last Update: 18 - 01 - 2023 (628506 entries)

Provided impact measures:
Popularity: Citation-based measure reflecting the current impact.
Influence: Citation-based measure reflecting the total impact.
Reader Attention: The current number of Mendeley readers.
Social Media Attention: The number of recent tweets related to this article.
*More details on these impact measures can be found here.
Score interpretations:
Exceptional score (in top 0.01%).
Substantial score (in top 1%).
Average score (in bottom 99%).
Score not available.
Main data sources:
CORD-19 dataset(1) (list of papers)
LitCovid hub(2) (list of papers)
PMC & PubMed (citations)
Mendeley (number of readers)
COVID-19-TweetIDs(3) (tweets)

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
1551UniProt: the universal protein knowledgebase in 2021  

The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.

Nucleic Acids Res2020       LitCov and CORD-19
1552Online Learning in the Face of COVID-19 Pandemic: Assessment of Students' Satisfaction at Chitwan Medical College of Nepal  

N/A

Kathmandu Univ Med J (KUMJ)2020       LitCov and CORD-19
1553Emergency Response to COVID-19 in Canada: Platform Development and Implementation for eHealth in Crisis Management  

BACKGROUND: Public health emergencies like epidemics put enormous pressure on health care systems while revealing deep structural and functional problems in the organization of care. The current coronavirus disease (COVID-19) pandemic illustrates this at a global level. The sudden increased demand on delivery systems puts unique pressures on pre-established care pathways. These extraordinary times require efficient tools for smart governance and resource allocation. OBJECTIVE: The aim of this study is to develop an innovative web-based solution addressing the seemingly insurmountable challenges of triaging, monitoring, and delivering nonhospital services unleashed by the COVID-19 pandemic. METHODS: An adaptable crisis management digital platform was envisioned and designed with the goal of improving the system’s response on the basis of the literature; an existing shared health record platform; and discussions between health care providers, decision makers, academia, and the private sector in response to the COVID 19 epidemic. RESULTS: The Crisis Management Platform was developed and offered to health authorities in Ontario on a nonprofit basis. It has the capability to dramatically streamline patient intake, triage, monitoring, referral, and delivery of nonhospital services. It decentralizes the provision of services (by moving them online) and centralizes data gathering and analysis, maximizing the use of existing human resources, facilitating evidence-based decision making, and minimizing the risk to both users and providers. It has unlimited scale-up possibilities (only constrained by human health risk resource availability) with minimal marginal cost. Similar web-based solutions have the potential to fill an urgent gap in resource allocation, becoming a unique asset for health systems governance and management during critical times. They highlight the potential effectiveness of web-based solutions if built on an outcome-driven architecture. CONCLUSIONS: Data and web-based approaches in response to a public health crisis are key to evidence-driven oversight and management of public health emergencies.

JMIR Public Health Surveill2020       LitCov and CORD-19
1554Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults  

AIM: The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%‐5% of diagnosed COVID‐19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID‐19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.

Acta Paediatr2020       LitCov and CORD-19
1555Care bundles for improving outcomes in patients with COVID-19 or related conditions in intensive care-a rapid scoping review  

N/A

Cochrane Database Syst Rev2020       LitCov and CORD-19
1556Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling  

Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs.

mBio2010       CORD-19
1557BCG revaccination of health workers in Brazil to improve innate immune responses against COVID-19: A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: The BCG vaccine, widely used in Brazil in new-borns, induces adjuvant protection for several diseases, including childhood virus infections. BCG activates monocytes and innate memory NK cells which are crucial for the antiviral immune response. Therefore, strategies to prevent COVID-19 in health workers (HW) should be carried out to prevent them becoming unwell so that they can continue to work during the pandemic. The hypothesis is that BCG will improve the innate immune response and prevent symptomatic infection or COVID-19 severity. The primary objective is to verify the effectiveness and safety of the BCG vaccine to prevent or reduce incidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the city of Goiânia (Brazil) among HW previously vaccinated with BCG and also its severity and mortality during the pandemic of the disease. Secondary objectives are to estimate the incidence of COVID-19 among these professionals and the innate immune response elicited to BCG. TRIAL DESIGN: This a phase II trial for repositioning BCG as a preventive strategy against COVID-19. The trial is an open-label, parallel-group randomised clinical trial, comparing HW vaccinated with BCG and HW not vaccinated. PARTICIPANTS: The trial will recruit 800 HW of Goiânia - Goiás, Brazil to reach a total of 400 HW included after comorbidities questioning and laboratorial evaluation. Eligibility criteria: Any HW presenting BCG vaccination scar with direct contact with suspected COVID-19 patients for at least 8 hours per week, whether in hospital beds, ICU, or in transportation or admission (nurses, doctors, physiotherapists, nutritionists, receptionists, etc.) who have negative IgM and IgG COVID-19 test. Participants with any of the following characteristics will be excluded: - Have had in the last fifteen days any signs or symptoms of virus infection, including COVID-19; - Have had fever in the last fifteen days; - Have been vaccinated fifteen days before the inclusion; - Have a history or confirmation of any immunosuppressive disease such as HIV, presented solid tumour in the last two years or autoimmune diseases; - Are under preventive medication with antibiotics, steroid anti-inflammatories, or chemotherapy; - Have less than 500 neutrophils per mL of blood; - Have previously been diagnosed with tuberculosis; - Are breastfeeding or pregnant; - Are younger than 18 years old; - Are participating as an investigator in this clinical trial. INTERVENTION AND COMPARATOR: HW will be randomized into the BCG vaccinated group or the BCG unvaccinated control group. The BCG vaccinated group will receive in the right arm, intradermally, a one off dose of 0.1 mL corresponding to approximately 2 x10(5) to 8 x10(5) CFU of live, freeze-dried, attenuated BCG Moscow 361-I, Bacillus Calmette Guerin vaccine (Serum Institute of India PVT. LTD.). The unvaccinated control group will not be vaccinated. The HW allocated in both groups will be followed up at specific times points until 180 days post inclusion. The vaccinated and control groups will be compared according to COVID-19 related outcomes. MAIN OUTCOMES: The primary outcomes are the incidence coefficient of infection by SARS-CoV-2 determined by RT-PCR of naso-oropharyngeal swab specimen or rapid lateral flow IgG and IgM test, and presence of general COVID-19 symptoms, disease severity and admission to hospital during the 180 days of follow up. The secondary outcome is the innate immune response elicited 15-20 days after vaccination. RANDOMISATION: The vaccine vial contains approximately 10 doses. In order to optimize the vaccine use, the randomisation was performed in blocks of 20 participants using the platform randomization.com [http://www.jerrydallal.com/random/permute.htm]. The randomization was prepared before any HW inclusion. The results were printed and inserted in sealed envelopes that were numbered with BCG-001 to BCG-400. The printed results as well the envelopes had the same numbers. At the time of the randomisation, each participant that meets the inclusion criteria will receive a consecutive participant number [BCG-001-BCG-400]. The sealed envelope with the assigned number, blinded to the researchers, will be opened in front of the participant and the arm allocation will be known. BLINDING (MASKING): There is no masking for the participants or for the healthcare providers. The study will be blinded to the laboratory researchers and to those who will be evaluating the outcomes and performing the statistical analyses. In this case, only the participant identification number will be available. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Four hundred heath workers will be randomised in two groups. Two hundred participants will be vaccinated, and 200 participants will not be vaccinated. TRIAL STATUS: The protocol approved by the Brazilian Ethical Committee is the seventh version, number CAAE: 31783720.0.0000.5078. The trial has been recruiting since September 20(th), 2020. The clinical trial protocol was registered on August 5(th), 2020. It is estimated that recruitment will finish by March 2021. TRIAL REGISTRATION: The protocol number was registered on August 5(th), 2020 at REBEC (Registro Brasileiro de Ensaios Clínicos). Register number: RBR-4kjqtg and WHO trial registration number UTN: U1111-1256-3892. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s13063-020-04822-0.

Trials2020       LitCov and CORD-19
1558Amplified ozone pollution in cities during the COVID-19 lockdown  

Abstract The effect of lockdown due to coronavirus disease (COVID-19) pandemic on air pollution in four Southern European cities (Nice, Rome, Valencia and Turin) and Wuhan (China) was quantified, with a focus on ozone (O3). Compared to the same period in 2017–2019, the daily O3 mean concentrations increased at urban stations by 24% in Nice, 14% in Rome, 27% in Turin, 2.4% in Valencia and 36% in Wuhan during the lockdown in 2020. This increase in O3 concentrations is mainly explained by an unprecedented reduction in NOx emissions leading to a lower O3 titration by NO. Strong reductions in NO2 mean concentrations were observed in all European cities, ~53% at urban stations, comparable to Wuhan (57%), and ~65% at traffic stations. NO declined even further, ~63% at urban stations and ~78% at traffic stations in Europe. Reductions in PM2.5 and PM10 at urban stations were overall much smaller both in magnitude and relative change in Europe (~8%) than in Wuhan (~42%). The PM reductions due to limiting transportation and fuel combustion in institutional and commercial buildings were partly offset by increases of PM emissions from the activities at home in some of the cities. The NOx concentrations during the lockdown were on average 49% lower than those at weekends of the previous years in all cities. The lockdown effect on O3 production was ~10% higher than the weekend effect in Southern Europe and 38% higher in Wuhan, while for PM the lockdown had the same effect as weekends in Southern Europe (~6% of difference). This study highlights the challenge of reducing the formation of secondary pollutants such as O3 even with strict measures to control primary pollutant emissions. These results are relevant for designing abatement policies of urban pollution.

Sci Total Environ2020       LitCov and CORD-19
1559Severe acute respiratory syndrome (SARS)  

N/A

Wkly Epidemiol Rec2003       CORD-19
1560Prediction of the COVID-19 Pandemic for the Top 15 Affected Countries: Advanced Autoregressive Integrated Moving Average (ARIMA) Model  

BACKGROUND: The coronavirus disease (COVID-19) pandemic has affected more than 200 countries and has infected more than 2,800,000 people as of April 24, 2020. It was first identified in Wuhan City in China in December 2019. OBJECTIVE: The aim of this study is to identify the top 15 countries with spatial mapping of the confirmed cases. A comparison was done between the identified top 15 countries for confirmed cases, deaths, and recoveries, and an advanced autoregressive integrated moving average (ARIMA) model was used for predicting the COVID-19 disease spread trajectories for the next 2 months. METHODS: The comparison of recent cumulative and predicted cases was done for the top 15 countries with confirmed cases, deaths, and recoveries from COVID-19. The spatial map is useful to identify the intensity of COVID-19 infections in the top 15 countries and the continents. The recent reported data for confirmed cases, deaths, and recoveries for the last 3 months was represented and compared between the top 15 infected countries. The advanced ARIMA model was used for predicting future data based on time series data. The ARIMA model provides a weight to past values and error values to correct the model prediction, so it is better than other basic regression and exponential methods. The comparison of recent cumulative and predicted cases was done for the top 15 countries with confirmed cases, deaths, and recoveries from COVID-19. RESULTS: The top 15 countries with a high number of confirmed cases were stratified to include the data in a mathematical model. The identified top 15 countries with cumulative cases, deaths, and recoveries from COVID-19 were compared. The United States, the United Kingdom, Turkey, China, and Russia saw a relatively fast spread of the disease. There was a fast recovery ratio in China, Switzerland, Germany, Iran, and Brazil, and a slow recovery ratio in the United States, the United Kingdom, the Netherlands, Russia, and Italy. There was a high death rate ratio in Italy and the United Kingdom and a lower death rate ratio in Russia, Turkey, China, and the United States. The ARIMA model was used to predict estimated confirmed cases, deaths, and recoveries for the top 15 countries from April 24 to July 7, 2020. Its value is represented with 95%, 80%, and 70% confidence interval values. The validation of the ARIMA model was done using the Akaike information criterion value; its values were about 20, 14, and 16 for cumulative confirmed cases, deaths, and recoveries of COVID-19, respectively, which represents acceptable results. CONCLUSIONS: The observed predicted values showed that the confirmed cases, deaths, and recoveries will double in all the observed countries except China, Switzerland, and Germany. It was also observed that the death and recovery rates were rose faster when compared to confirmed cases over the next 2 months. The associated mortality rate will be much higher in the United States, Spain, and Italy followed by France, Germany, and the United Kingdom. The forecast analysis of the COVID-19 dynamics showed a different angle for the whole world, and it looks scarier than imagined, but recovery numbers start looking promising by July 7, 2020.

JMIR Public Health Surveill2020       LitCov and CORD-19
1561The Impact of COVID-19 Epidemic Declaration on Psychological Consequences: A Study on Active Weibo Users  

COVID-19 (Corona Virus Disease 2019) has significantly resulted in a large number of psychological consequences. The aim of this study is to explore the impacts of COVID-19 on people’s mental health, to assist policy makers to develop actionable policies, and help clinical practitioners (e.g., social workers, psychiatrists, and psychologists) provide timely services to affected populations. We sample and analyze the Weibo posts from 17,865 active Weibo users using the approach of Online Ecological Recognition (OER) based on several machine-learning predictive models. We calculated word frequency, scores of emotional indicators (e.g., anxiety, depression, indignation, and Oxford happiness) and cognitive indicators (e.g., social risk judgment and life satisfaction) from the collected data. The sentiment analysis and the paired sample t-test were performed to examine the differences in the same group before and after the declaration of COVID-19 on 20 January, 2020. The results showed that negative emotions (e.g., anxiety, depression and indignation) and sensitivity to social risks increased, while the scores of positive emotions (e.g., Oxford happiness) and life satisfaction decreased. People were concerned more about their health and family, while less about leisure and friends. The results contribute to the knowledge gaps of short-term individual changes in psychological conditions after the outbreak. It may provide references for policy makers to plan and fight against COVID-19 effectively by improving stability of popular feelings and urgently prepare clinical practitioners to deliver corresponding therapy foundations for the risk groups and affected people.

Int J Environ Res Public Healt2020       LitCov and CORD-19
1562Serial measurements in COVID-19 induced acute respiratory disease to unravel heterogeneity of the disease course: design of the Maastricht Intensive Care COVID cohort (MaastrICCht)  

INTRODUCTION: The course of the disease in SARS-CoV-2 infection in mechanically ventilated patients is unknown. To unravel the clinical heterogeneity of the SARS-CoV-2 infection in these patients, we designed the prospective observational Maastricht Intensive Care COVID cohort (MaastrICCht). We incorporated serial measurements that harbour aetiological, diagnostic and predictive information. The study aims to investigate the heterogeneity of the natural course of critically ill patients with a SARS-CoV-2 infection. METHODS AND ANALYSIS: Mechanically ventilated patients admitted to the intensive care with a SARS-CoV-2 infection will be included. We will collect clinical variables, vital parameters, laboratory variables, mechanical ventilator settings, chest electrical impedance tomography, ECGs, echocardiography as well as other imaging modalities to assess heterogeneity of the course of a SARS-CoV-2 infection in critically ill patients. The MaastrICCht is also designed to foster various other studies and registries and intends to create an open-source database for investigators. Therefore, a major part of the data collection is aligned with an existing national intensive care data registry and two international COVID-19 data collection initiatives. Additionally, we create a flexible design, so that additional measures can be added during the ongoing study based on new knowledge obtained from the rapidly growing body of evidence. The spread of the COVID-19 pandemic requires the swift implementation of observational research to unravel heterogeneity of the natural course of the disease of SARS-CoV-2 infection in mechanically ventilated patients. Our study design is expected to enhance aetiological, diagnostic and prognostic understanding of the disease. This paper describes the design of the MaastrICCht. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the medical ethics committee (Medisch Ethische Toetsingscommissie 2020-1565/3 00 523) of the Maastricht University Medical Centre+ (Maastricht UMC+), which will be performed based on the Declaration of Helsinki. During the pandemic, the board of directors of Maastricht UMC+ adopted a policy to inform patients and ask their consent to use the collected data and to store serum samples for COVID-19 research purposes. All study documentation will be stored securely for fifteen years after recruitment of the last patient. The results will be published in peer-reviewed academic journals, with a preference for open access journals, while particularly considering deposition of the manuscripts on a preprint server early. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NL8613).

BMJ Open2020       LitCov and CORD-19
1563Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China  

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.

Kidney Int2020       LitCov and CORD-19
1564Patient and clinician experience with a rapidly implemented large-scale video consultation program during COVID-19  

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has forced health-care providers to find creative ways to allow continuity of care in times of lockdown. Telemedicine enables provision of care when in-person visits are not possible. Sheba Medical Center made a rapid transition of outpatient clinics to video consultations (VC) during the first wave of COVID-19 in Israel. OBJECTIVE: Results of a survey of patient and clinician user experience with VC are reported. METHODS: Satisfaction surveys were sent by text messages to patients, clinicians who practice VC (users) and clinicians who do not practice VC (non-users). Questions referred to general satisfaction, ease of use, technical issues and medical and communication quality. Questions and scales were based on surveys used regularly in outpatient clinics of Sheba Medical Center. RESULTS: More than 1200 clinicians (physicians, psychologists, nurses, social workers, dietitians, speech therapists, genetic consultants and others) provided VC during the study period. Five hundred and forty patients, 162 clinicians who were users and 50 clinicians who were non-users completed the survey. High level of satisfaction was reported by 89.8% of patients and 37.7% of clinician users. Technical problems were experienced by 21% of patients and 80% of clinician users. Almost 70% of patients but only 23.5% of clinicians found the platform very simple to use. Over 90% of patients were very satisfied with clinician’s courtesy, expressed a high sense of trust, thought that clinician’s explanations and recommendations were clear and estimated that the clinician understood their problems and 86.5% of them would recommend VC to family and friends. Eighty-seven percent of clinician users recognize the benefit of VC for patients during the COVID-19 pandemic but only 68% supported continuation of the service after the pandemic. CONCLUSION: Our study reports high levels of patient satisfaction from outpatient clinics VC during the COVID-19 pandemic. Lower levels of clinician satisfaction can mostly be attributed to technical and administrative challenges related to the newly implemented telemedicine platform. Our findings support the continued future use of VC as a means of providing patient-centered care. Future steps need to be taken to continuously improve the clinical and administrative application of telemedicine services.

Int J Qual Healthcare2020       LitCov and CORD-19
1565Public mental health under the long-term influence of COVID-19 in China: Geographical and temporal distribution  

BACKGROUND: The mental health status caused by major epidemics is serious and lasting. At present, there are few studies about the lasting mental health effects of COVID-19 outbreak. The purpose of this study was to investigate the mental health of the Chinese public during the long-term COVID-19 outbreak. METHODS: A total of 1172 online questionnaires were collected, covering demographical information and 8 common psychological states: depression, anxiety, somatization, stress, psychological resilience, suicidal ideation and behavior, insomnia, and stress disorder. In addition, the geographical and temporal distributions of different mental states were plotted. RESULTS: Overall, 30.1% of smokers increased smoking, while 11.3% of drinkers increased alcohol consumption. The prevalence rates of depression, anxiety, mental health problems, high risk of suicidal and behavior, clinical insomnia, clinical post-traumatic stress disorder symptoms, moderate-to-high levels of perceived stress were 18.8%, 13.3%, 7.6%, 2.8%, 7.2%, 7.0%, and 67.9%, respectively. Further, the geographical distribution showed that the mental status in some provinces/autonomous regions/municipalities was relatively more serious. The temporal distribution showed that the psychological state of the participants was relatively poorer on February 20, 24 to 26 and March 25, especially on March 25. LIMITATIONS: This cross-sectional design cannot make causal inferences. And the snowball sampling was not representative enough. CONCLUSION: Our findings suggest that the prevalence rate of mental disorders in the Chinese public is relatively low in the second month of the COVID-19 pandemic. In addition, people's mental state is affected by the geographical and temporal distributions.

J Affect Disord2020       LitCov and CORD-19
1566Effects of different types of written vaccination information on COVID-19 vaccine hesitancy in the UK (OCEANS-III): a single-blind, parallel-group, randomised controlled trial  

BACKGROUND: The effectiveness of the COVID-19 vaccination programme depends on mass participation: the greater the number of people vaccinated, the less risk to the population. Concise, persuasive messaging is crucial, particularly given substantial levels of vaccine hesitancy in the UK. Our aim was to test which types of written information about COVID-19 vaccination, in addition to a statement of efficacy and safety, might increase vaccine acceptance. METHODS: For this single-blind, parallel-group, randomised controlled trial, we aimed to recruit 15 000 adults in the UK, who were quota sampled to be representative. Participants were randomly assigned equally across ten information conditions stratified by level of vaccine acceptance (willing, doubtful, or strongly hesitant). The control information condition comprised the safety and effectiveness statement taken from the UK National Health Service website; the remaining conditions addressed collective benefit, personal benefit, seriousness of the pandemic, and safety concerns. After online provision of vaccination information, participants completed the Oxford COVID-19 Vaccine Hesitancy Scale (outcome measure; score range 7–35) and the Oxford Vaccine Confidence and Complacency Scale (mediation measure). The primary outcome was willingness to be vaccinated. Participants were analysed in the groups they were allocated. p values were adjusted for multiple comparisons. The study was registered with ISRCTN, ISRCTN37254291. FINDINGS: From Jan 19 to Feb 5, 2021, 15 014 adults were recruited. Vaccine hesitancy had reduced from 26·9% the previous year to 16·9%, so recruitment was extended to Feb 18 to recruit 3841 additional vaccine-hesitant adults. 12 463 (66·1%) participants were classified as willing, 2932 (15·6%) as doubtful, and 3460 (18·4%) as strongly hesitant (ie, report that they will avoid being vaccinated for as long as possible or will never get vaccinated). Information conditions did not alter COVID-19 vaccine hesitancy in those willing or doubtful (adjusted p values >0·70). In those strongly hesitant, COVID-19 vaccine hesitancy was reduced, in comparison to the control condition, by personal benefit information (mean difference –1·49, 95% CI –2·16 to –0·82; adjusted p=0·0015), directly addressing safety concerns about speed of development (−0·91, –1·58 to –0·23; adjusted p=0·0261), and a combination of all information (−0·86, –1·53 to –0·18; adjusted p=0·0313). In those strongly hesitant, provision of personal benefit information reduced hesitancy to a greater extent than provision of information on the collective benefit of not personally getting ill (−0·97, 95% CI –1·64 to –0·30; adjusted p=0·0165) or the collective benefit of not transmitting the virus (−1·01, –1·68 to –0·35; adjusted p=0·0150). Ethnicity and gender were found to moderate information condition outcomes. INTERPRETATION: In the approximately 10% of the population who are strongly hesitant about COVID-19 vaccines, provision of information on personal benefit reduces hesitancy to a greater extent than information on collective benefits. Where perception of risk from vaccines is most salient, decision making becomes centred on the personal. As such, messaging that stresses the counterbalancing personal benefits is likely to prove most effective. The messaging from this study could be used in public health communications. Going forwards, the study highlights the need for future health campaigns to engage with the public on the terrain that is most salient to them. FUNDING: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and NIHR Oxford Health Biomedical Research Centre.

Lancet Public Health2021       LitCov and CORD-19
1567Real-time RT-PCR in COVID-19 detection: issues affecting the results  

Expert Rev Mol Diagn2020       LitCov and CORD-19
1568Selecting a SARS-CoV-2/COVID molecular testing method for your laboratory  

In early March 2020 it became apparent that clinical laboratories would need to quickly develop strategies for SARS-CoV-2/COVID-19 testing. For most, the initial approach was to send out testing to a reference laboratory. As the pandemic has progressed, the food and drug administration (FDA) has allowed for several manufacturers to make testing reagents commercially available. Concurrently, the demand for rapid accessibility of results persists, leading many laboratories to evaluate options for “in house” testing. This reflection highlights some of the considerations when selecting the best method for your laboratory, with specific examples highlighted from a medium volume laboratory’s experience.

J Appl Lab Med2020       LitCov and CORD-19
1569SARS-CoV-2 Vaccines: Status Report  

SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population.

Immunity2020       LitCov and CORD-19
1570Labour Market Attachment, Workplace Infection Control Procedures and Mental Health: A Cross-Sectional Survey of Canadian Non-healthcare Workers during the COVID-19 Pandemic  

BACKGROUND: The COVID-19 pandemic has led to large proportions of the labour market moving to remote work, while others have become unemployed. Those still at their physical workplace likely face increased risk of infection, compared to other workers. The objective of this paper is to understand the relationship between working arrangements, infection control programs (ICP), and symptoms of anxiety and depression among Canadian workers, not specifically working in healthcare. METHODS: A convenience-based internet survey of Canadian non-healthcare workers was facilitated through various labour organizations between April 26 and June 6, 2020. A total of 5180 respondents started the survey, of which 3779 were assessed as employed in a full-time or part-time capacity on 2 March 2020 (prior to large-scale COVID-19 pandemic responses in Canada). Of this sample, 3305 (87.5%) had complete information on main exposures and outcomes. Anxiety symptoms were measured using the Generalised Anxiety Disorder screener (GAD-2), and depressive symptoms using the Patient Health Questionnaire screener (PHQ-2). For workers at their physical workplace (site-based workers) we asked questions about the adequacy and implementation of 11 different types of ICP, and the adequacy and supply of eight different types of personal protective equipment (PPE). Respondents were classified as either: working remotely; site-based workers with 100% of their ICP/PPE needs met; site-based workers with 50–99% of ICP/PPE needs met; site-based workers with 1–49% of ICP/PPE needs met; site-based workers with none of ICP/PPE needs met; or no longer employed. Regression analyses examined the association between working arrangements and ICP/PPE adequacy and having GAD-2 and PHQ-2 scores of three and higher (a common screening point in both scales). Models were adjusted for a range of demographic, occupation, workplace, and COVID-19-specific factors. RESULTS: A total of 42.3% (95% CI: 40.6–44.0%) of the sample had GAD-2 scores of 3 and higher, and 34.6% (95% CI: 32.–36.2%) had PHQ-2 scores of 3 and higher. In initial analyses, symptoms of anxiety and depression were lowest among those working remotely (35.4 and 27.5%), compared to site-based workers (43.5 and 34.7%) and those who had lost their jobs (44.1 and 35.9%). When adequacy of ICP and PPE was taken into account, the lowest prevalence of anxiety and depressive symptoms was observed among site-based workers with all of their ICP needs being met (29.8% prevalence for GAD-2 scores of 3 and higher, and 23.0% prevalence for PHQ-2 scores of 3 and higher), while the highest prevalence was observed among site-based workers with none of their ICP needs being met (52.3% for GAD-2 scores of 3 and higher, and 45.8% for PHQ-2 scores of 3 and higher). CONCLUSION: Our results suggest that the adequate design and implementation of employer-based ICP have implications for the mental health of site-based workers. As economies re-open the ongoing assessment of ICP and associated mental health outcomes among the workforce is warranted.

Ann Work Expo Health2020       LitCov and CORD-19
1571Potential false-negative nucleic acid testing results for SARS-CoV-2 from thermal inactivation of samples with low viral loads  

BACKGROUND: Corona Virus Disease-2019 (COVID-19) has spread widely throughout the world since the end of 2019. Nucleic acid testing (NAT) has played an important role in patient diagnosis and management of COVID-19. In some circumstances, thermal inactivation at 56 °C has been recommended to inactivate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) before NAT. However, this procedure could theoretically disrupt nucleic acid integrity of this single-stranded RNA virus and cause false negatives in real-time polymerase chain reaction (RT-PCR) tests. METHODS: We investigated whether thermal inactivation could affect the results of viral NAT. We examined the effects of thermal inactivation on the quantitative RT-PCR results of SARS-CoV-2 particularly with regard to the rates of false-negative results for specimens carrying low viral loads. We additionally investigated the effects of different specimen types, sample preservation times and a chemical inactivation approach on NAT. RESULTS: Our work showed increased Ct values in specimens from diagnosed COVID-19 patients in RT-PCR tests after thermal incubation. Moreover, about half of the weak-positive samples (7 of 15 samples, 46.7%) were RT-PCR negative after heat inactivation in at least one parallel testing. The use of guanidinium-based lysis for preservation of these specimens had a smaller impact on RT-PCR results with fewer false negatives (2 of 15 samples, 13.3%) and significantly less increase in Ct values than heat inactivation. CONCLUSION: Thermal inactivation adversely affected the efficiency of RT-PCR for SARS-CoV-2 detection. Given the limited applicability associated with chemical inactivators, other approaches to ensure the overall protection of laboratory personnel need consideration.

Clin Chem2020       LitCov and CORD-19
1572Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus  

BACKGROUND: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. METHODS: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein–protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program. RESULTS: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian. CONCLUSIONS: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.

J Transl Med2020       LitCov and CORD-19
1573Curtailing transmission of severe acute respiratory syndrome within a community and its hospital  

N/A

Proc Biol Sci2003       CORD-19
1574Identification of probable genomic packaging signal sequence from SARS-CoV genome by bioinformatics analysis  

N/A

Acta Pharmacol Sin2003       CORD-19
1575Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association  

N/A

Proc Natl Acad Sci U S A2004       CORD-19
1576Severe acute respiratory syndrome: the first transmissible disease of the 21st century  

N/A

Recenti Prog Med2003       CORD-19
1577Bats as a continuing source of emerging infections in humans  

Amongst the 60 viral species reported to be associated with bats, 59 are RNA viruses, which are potentially important in the generation of emerging and re‐emerging infections in humans. The prime examples of these are the lyssaviruses and Henipavirus. The transmission of Nipah, Hendra and perhaps SARS coronavirus and Ebola virus to humans may involve intermediate amplification hosts such as pigs, horses, civets and primates, respectively. Understanding of the natural reservoir or introductory host, the amplifying host, the epidemic centre and at‐risk human populations are crucial in the control of emerging zoonosis. The association between the bat coronaviruses and certain lyssaviruses with particular bat species implies co‐evolution between specific viruses and bat hosts. Cross‐infection between the huge number of bat species may generate new viruses which are able to jump the trans‐mammalian species barrier more efficiently. The currently known viruses that have been found in bats are reviewed and the risks of transmission to humans are highlighted. Certain families of bats including the Pteropodidae, Molossidae, Phyllostomidae, and Vespertilionidae are most frequently associated with known human pathogens. A systematic survey of bats is warranted to better understand the ecology of these viruses. Copyright © 2006 John Wiley & Sons, Ltd.

Rev Med Virol2006       CORD-19
1578Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2  

Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV–host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2.

Cell Discov2020       LitCov and CORD-19
1579Mental Health and Psychosocial Problems of Medical Health Workers during the COVID-19 Epidemic in China  

OBJECTIVE: We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak. METHODS: An online survey was run from February 19 to March 6, 2020; a total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2). RESULTS: Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05). CONCLUSIONS: During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.

Psychother Psychosom2020       LitCov and CORD-19
1580COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning  

To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane (M) protein, have been tested for vaccine development against SARS and MERS. However, these vaccine candidates might lack the induction of complete protection and have safety concerns. We then applied the Vaxign and the newly developed machine learning-based Vaxign-ML reverse vaccinology tools to predict COVID-19 vaccine candidates. Our Vaxign analysis found that the SARS-CoV-2 N protein sequence is conserved with SARS-CoV and MERS-CoV but not from the other four human coronaviruses causing mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8-10), were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and the predicted linear B-cell epitopes were found to be localized on the surface of the protein. Our predicted vaccine targets have the potential for effective and safe COVID-19 vaccine development. We also propose that an “Sp/Nsp cocktail vaccine” containing a structural protein(s) (Sp) and a non-structural protein(s) (Nsp) would stimulate effective complementary immune responses.

Front Immunol2020       LitCov and CORD-19
1581Serial Testing for SARS-CoV-2 and Virus Whole Genome Sequencing Inform Infection Risk at Two Skilled Nursing Facilities with COVID-19 Outbreaks-Minnesota, April-June 2020  

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly in high-risk congregate settings such as skilled nursing facilities (SNFs) (1). In Minnesota, SNF-associated cases accounted for 3,950 (8%) of 48,711 COVID-19 cases reported through July 21, 2020; 35% of SNF-associated cases involved health care personnel (HCP*), including six deaths. Facility-wide, serial testing in SNFs has been used to identify residents with asymptomatic and presymptomatic SARS-CoV-2 infection to inform mitigation efforts, including cohorting of residents with positive test results and exclusion of infected HCP from the workplace (2,3). During April-June 2020, the Minnesota Department of Health (MDH), with CDC assistance, conducted weekly serial testing at two SNFs experiencing COVID-19 outbreaks. Among 259 tested residents, and 341 tested HCP, 64% and 33%, respectively, had positive reverse transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 test results. Continued SARS-CoV-2 transmission was potentially facilitated by lapses in infection prevention and control (IPC) practices, up to 12-day delays in receiving HCP test results (53%) at one facility, and incomplete HCP participation (71%). Genetic sequencing demonstrated that SARS-CoV-2 viral genomes from HCP and resident specimens were clustered by facility, suggesting facility-based transmission. Residents and HCP working in SNFs are at risk for infection with SARS-CoV-2. As part of comprehensive COVID-19 preparation and response, including early identification of cases, SNFs should conduct serial testing of residents and HCP, maximize HCP testing participation, ensure availability of personal protective equipment (PPE), and enhance IPC practices† (4-5).

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
1582Liver injury in COVID-19: management and challenges  

Lancet Gastroenterol Hepatol2020       LitCov and CORD-19
1583Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes  

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral–fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral–fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

Emerg Microbes Infect2020       LitCov and CORD-19
1584COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis and treatment options  

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Cardiovasc Res2020       LitCov and CORD-19
1585Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2  

Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.

EMBO J2005       CORD-19
1586Initial chest radiographs and artificial intelligence (AI) predict clinical outcomes in COVID-19 patients: analysis of 697 Italian patients  

OBJECTIVE: To evaluate whether the initial chest X-ray (CXR) severity assessed by an AI system may have prognostic utility in patients with COVID-19. METHODS: This retrospective single-center study included adult patients presenting to the emergency department (ED) between February 25 and April 9, 2020, with SARS-CoV-2 infection confirmed on real-time reverse transcriptase polymerase chain reaction (RT-PCR). Initial CXRs obtained on ED presentation were evaluated by a deep learning artificial intelligence (AI) system and compared with the Radiographic Assessment of Lung Edema (RALE) score, calculated by two experienced radiologists. Death and critical COVID-19 (admission to intensive care unit (ICU) or deaths occurring before ICU admission) were identified as clinical outcomes. Independent predictors of adverse outcomes were evaluated by multivariate analyses. RESULTS: Six hundred ninety-seven 697 patients were included in the study: 465 males (66.7%), median age of 62 years (IQR 52–75). Multivariate analyses adjusting for demographics and comorbidities showed that an AI system-based score ≥ 30 on the initial CXR was an independent predictor both for mortality (HR 2.60 (95% CI 1.69 − 3.99; p < 0.001)) and critical COVID-19 (HR 3.40 (95% CI 2.35–4.94; p < 0.001)). Other independent predictors were RALE score, older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. CONCLUSION: AI- and radiologist-assessed disease severity scores on CXRs obtained on ED presentation were independent and comparable predictors of adverse outcomes in patients with COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318366 (https://clinicaltrials.gov/ct2/show/NCT04318366). KEY POINTS: • AI system–based score ≥ 30 and a RALE score ≥ 12 at CXRs performed at ED presentation are independent and comparable predictors of death and/or ICU admission in COVID-19 patients. • Other independent predictors are older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. • The comparable performance of the AI system in relation to a radiologist-assessed score in predicting adverse outcomes may represent a game-changer in resource-constrained settings.

Eur Radiol2020       LitCov and CORD-19
1587COVID-19: the gendered impacts of the outbreak  

Lancet2020       LitCov and CORD-19
1588A Nationwide Survey of Psychological Distress among Italian People during the COVID-19 Pandemic: Immediate Psychological Responses and Associated Factors  

The uncontrolled spread of the coronavirus disease 2019 (COVID-19) has called for unprecedented measures, to the extent that the Italian government has imposed a quarantine on the entire country. Quarantine has a huge impact and can cause considerable psychological strain. The present study aims to establish the prevalence of psychiatric symptoms and identify risk and protective factors for psychological distress in the general population. An online survey was administered from 18–22 March 2020 to 2766 participants. Multivariate ordinal logistic regression models were constructed to examine the associations between sociodemographic variables; personality traits; depression, anxiety, and stress. Female gender, negative affect, and detachment were associated with higher levels of depression, anxiety, and stress. Having an acquaintance infected was associated with increased levels of both depression and stress, whereas a history of stressful situations and medical problems was associated with higher levels of depression and anxiety. Finally, those with a family member infected and young person who had to work outside their domicile presented higher levels of anxiety and stress, respectively. This epidemiological picture is an important benchmark for identifying persons at greater risk of suffering from psychological distress and the results are useful for tailoring psychological interventions targeting the post-traumatic nature of the distress.

Int J Environ Res Public Healt2020       LitCov and CORD-19
1589Sleep quality and mental health in the context of COVID-19 pandemic and lockdown in Morocco  

• High prevalence of sleep disorders, anxiety, and depressive signs were found in COVID-19 pandemic and lockdown. • False believes on sleep concepts were assessed. • Such false believes were presenting a risk factor of sleep disorders, anxiety, and depression. • A program of sensitization should be initiated to fight against false sleep beliefs. • Valuing protection procedures of health workers and all high-risk people. • Offer better access to provided psychological support through dedicated setup.

Sleep Med2020       LitCov and CORD-19
1590Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer and Placental Pathology in Pregnancies During the COVID-19 Pandemic  

IMPORTANCE: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti–SARS-CoV-2 antibody, and incidence of fetoplacental infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription–polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. EXPOSURES: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. MAIN OUTCOMES AND MEASURES: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti–SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. RESULTS: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti–receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti–SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti–receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted. CONCLUSIONS AND RELEVANCE: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

JAMA Netw Open2020       LitCov and CORD-19
1591Authors' Reply to: Errors in Tracing Coronavirus SARS-CoV-2 Transmission Using a Maximum Likelihood Tree. Comment on "A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis"  

JMIR Public Health Surveill2020       LitCov and CORD-19
1592Proliferative growth of SARS coronavirus in Vero E6 cells  

N/A

J Gen Virol2003       CORD-19
1593SARS related preventive and risk behaviours practised by Hong Kong-mainland China cross border travellers during the outbreak of the SARS epidemic in Hong Kong  

N/A

J Epidemiol Community Health2004       CORD-19
1594In silico identification of potential inhibitors of key SARS-CoV-2 3CL hydrolase (Mpro) via molecular docking, MMGBSA predictive binding energy calculations and molecular dynamics simulation  

The incidence of 2019 novel corona virus (SARS-CoV-2) has created a medical emergency throughout the world. Various efforts have been made to develop the vaccine or effective treatments against the disease. The discovery of crystal structure of SARS-CoV-2 main protease has made the in silico identification of its inhibitors possible. Based on its critical role in viral replication, the viral protease can prove to be a promising “target” for antiviral drug therapy. We have systematically screened an in-house library of 15,754 natural and synthetic compounds, established at International Center for Chemical and Biological Sciences, University of Karachi. The in silico search for potential viral protease inhibitors resulted in nine top ranked ligands (compounds 1–9) against SARS-CoV-2 main protease (PDB ID: 6LU7) based on docking scores, and predictive binding energies. The in silico studies were updated via carrying out the docking, and predictive binding energy estimation, with a recently reported crystal structure of main protease (PDB ID: 6Y2F) at a better resolution i.e., 1.95 Å. Compound 2 (molecular bank code AAA396) was found to have highest negative binding energy of −71.63 kcal/mol for 6LU7. While compound 3 (molecular bank code AAD146) exhibited highest negative binding energy of -81.92 kcal/mol for 6Y2F. The stability of the compounds- in complex with viral protease was analyzed by Molecular Dynamics simulation studies, and was found to be stable over the course of 20 ns simulation time. Compound 2, and 3 were predicted to be the significant inhibitors of SARS-CoV-2 3CL hydrolase (Mpro) among the nine short listed compounds.

PLoS One2020       LitCov and CORD-19
1595COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T-cell responses  

N/A

Nature2020       LitCov and CORD-19
1596Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds  

The 3C-like protease (3CL(pro)) of SARS-coronavirus mediates the proteolytic processing of replicase polypeptides 1a and 1ab into functional proteins, becoming an important target for the drug development. In this study, Isatis indigotica root extract, five major compounds of I. indigotica root, and seven plant-derived phenolic compounds were tested for anti-SARS-CoV 3CL(pro) effects using cell-free and cell-based cleavage assays. Cleavage assays with the 3CL(pro) demonstrated that IC(50) values were in micromolar ranges for I. indigotica root extract, indigo, sinigrin, aloe emodin and hesperetin. Sinigrin (IC(50): 217 μM) was more efficient in blocking the cleavage processing of the 3CL(pro) than indigo (IC(50): 752 μM) and beta-sitosterol (IC(50): 1210 μM) in the cell-based assay. Only two phenolic compounds aloe emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CL(pro), in which the IC(50) was 366 μM for aloe emodin and 8.3 μM for hesperetin in the cell-based assay.

Antiviral Res2005       CORD-19
1597Is returning to work during the COVID-19 pandemic stressful? A study on immediate mental health status and psychoneuroimmunity prevention measures of Chinese workforce  

Abstract This study aimed to quantify the immediate psychological effects and psychoneuroimmunity prevention measures of a workforce returning to work during the COVID-19 epidemic. Workforce returning to work was invited to complete an online questionnaire regarding their attitude toward the COVID-19 epidemic and return-to-work along with psychological parameters including the Impact of Event Scale-Revised, Depression, Anxiety, Stress Scale- 21 (DASS-21) and Insomnia Severity Index (ISI). Psychoneuroimmunity prevention measures include precautions at personal and organization levels. From 673 valid questionnaires, we found that 10.8% of respondents met the diagnosis of post-traumatic stress disorder (PTSD) after returning to work. The respondents reported a low prevalence of anxiety (3.8%), depression (3.7%), stress (1.5%) and insomnia (2.3%). There were no significant differences in the severity of psychiatric symptoms between workers/technicians and executives/managers. More than 95% reported psychoneuroimmunity prevention measures including good ventilation in the workplace and wore a face mask as protective. Factors that were associated with the severity of psychiatric symptoms in the workforce were marital status, presence of physical symptom, poor physical health and viewing return to work as a health hazard (p<0.05). In contrast, personal psychoneuroimmunity prevention measures including hand hygiene and wearing face masks as well as organizational measures including significant improvement of workplace hygiene and concerns from the company were associated with less severe psychiatric symptoms (p<0.05). Contrary to expectations, returning to work had not caused a high level of psychiatric symptoms in the workforce. The low prevalence of psychiatric symptoms could be due to confidence instilled by psychoneuroimmunity prevention measures before the resumption of work. Our findings would provide information for other countries during the COVID-19 pandemic.

Brain Behav Immun2020       LitCov and CORD-19
1598Life in lockdown: A telephone survey to investigate the impact of COVID-19 lockdown measures on the lives of older people (≥75 years)  

Background: In response to the COVID-19 coronavirus pandemic, the UK government introduced social distancing measures and identified specific populations at high risk from the virus. People ≥70 were deemed “Clinically Vulnerable.” Distancing measures were introduced to reduce the risk of contracting COVID-19. However, these may have a negative impact on older people who are vulnerable to social isolation and may have challenges accessing services and provisions. Objectives: To investigate the impact of COVID-19 lockdown measures on the lives of older people. Study design and setting: Cross-sectional telephone survey. Participants: Community-dwelling older people, 76–97 years. Outcomes: Health anxiety; General health (RAND Short-form 36 Survey); Physical activity; Depression (PHQ-8); Anxiety (GAD-2); Loneliness; Access to services; Challenges, concerns and positive experiences. Data analysis: Counts (%), means (SDs). Thematic analysis was used to identify themes from open questions. Results: n = 142. 52% did not worry about their health; 76% rated their health as “good”, “very good” or “excellent”. < 10% met the criteria indicative of depression (PHQ-8), or anxiety (GAD-2). 42% were less active than before lockdown. 27% were lonely at least some of the time. Over half of participants identified positive aspects. Conclusions: Most participants reported good health with low levels of health anxiety, anxiety and depression. Many were able to identify positive aspects to lockdown and may be better equipped to deal with lockdown than anticipated. Strategies may be required to ameliorate the negative impact of loneliness for a minority of older people, and help some resume previous activity levels and pursuits.

Age Ageing2020       LitCov and CORD-19
1599Ethical and legal challenges posed by severe acute respiratory syndrome: implications for the control of severe infectious disease threats  

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JAMA2003       CORD-19
1600Anti-SARS-CoV-2 Immunoglobulin Isotypes and Neutralization Activity Against Viral Variants, According to BNT162b2-Vaccination and Infection History  

PURPOSE: To compare SARS-CoV-2 antigen-specific antibody production and plasma neutralizing capacity against B.1 wild-type-like strain, and Gamma/P.1 and Delta/B.1.617.2 variants-of-concern, in subjects with different Covid-19 disease and vaccination histories. METHODS: Adult subjects were: 1) Unvaccinated/hospitalized for Covid-19; 2) Covid-19-recovered followed by one BNT162b2 vaccine dose; and 3) Covid-19-naïve/2-dose BNT162b2 vaccinated. Multiplex Luminex(®) immunoassays measured IgG, IgA, and IgM plasma levels against SARS-CoV-2 receptor-binding domain (RBD), spike-1 (S), and nucleocapsid proteins. Neutralizing activity was determined in Vero E6 cytopathic assays. RESULTS: Maximum anti-RBD IgG levels were similar in Covid(-)19‑recovered individuals 8‒10 days after single-dose vaccination and in Covid-19-naïve subjects 7 days after 2(nd) vaccine dosing; both groups had ≈2‑fold higher anti-RBD IgG levels than Unvaccinated/Covid-19 subjects tracked through 2 weeks post-symptom onset. Anti-S IgG expression patterns were similar to RBD within each group, but with lower signal strengths. Viral antigen-specific IgA and IgM levels were more variable than IgG patterns. Anti-nucleocapsid immunoglobulins were not detected in Covid-19-naïve subjects. Neutralizing activity against the B.1 strain, and Gamma/P.1 and Delta/B.1.617.2 variants, was highest in Covid‑19-recovered/single-dose vaccinated subjects; although neutralization against the Delta variant in this group was only 26% compared to B.1 neutralization, absolute anti-Delta titers suggested maintained protection. Neutralizing titers against the Gamma and Delta variants were 33‒77% and 26‒67%, respectively, versus neutralization against the B.1 strain (100%) in the three groups. CONCLUSION: These findings support SARS-CoV-2 mRNA vaccine usefulness regardless of Covid-19 history, and confirm remarkable protection provided by a single vaccine dose in people who have recovered from Covid-19.

Front Immunol2021       LitCov and CORD-19

(1) COVID-19 Open Research Dataset (CORD-19). 2020. Version 2022-06-02. Retrieved from https://ai2-semanticscholar-cord-19.s3-us-west-2.amazonaws.com/historical_releases.html. Accessed 2022-06-05. doi:10.5281/zenodo.3715506
(2) Chen Q, Allot A, & Lu Z. (2020) Keep up with the latest coronavirus research, Nature 579:193 and Chen Q, Allot A, Lu Z. LitCovid: an open database of COVID-19 literature. Nucleic Acids Research. 2020. (version 2023-01-10)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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