\ 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
1001Pre-Vaccine Positivity of SARS-CoV-2 Antibodies in Alberta, Canada during the First Two Waves of the COVID-19 Pandemic  

We systematically evaluated SARS-CoV-2 IgG positivity in a provincial cohort to understand the local epidemiology of COVID-19 and support evidence-based public health decisions. Residual blood samples were collected for serology testing over 5-day periods monthly from June 2020 to January 2021 from six clinical laboratories across the province of Alberta, Canada. A total of 93,993 individual patient samples were tested with a SARS-CoV-2 nucleocapsid antibody assay with positives confirmed using a spike antibody assay. Population-adjusted SARS-CoV-2 IgG seropositivity was 0.92% (95% confidence interval [CI]: 0.91 to 0.93%) shortly after the first COVID-19 wave in June 2020, increasing to 4.63% (95% CI: 4.61 to 4.65%) amid the second wave in January 2021. There was no significant difference in seropositivity between males and females (1.39% versus 1.27%; P = 0.11). Ages with highest seropositivity were 0 to 9 years (2.71%, 95% CI: 1.64 to 3.78%) followed by 20 to 29 years (1.58%, 95% CI: 1.12 to 2.04%), with the lowest rates seen in those aged 70 to 79 (0.79%, 95% CI: 0.65 to 0.93%) and >80 (0.78%, 95% CI: 0.60 to 0.97%). Compared to the seronegative group, seropositive patients inhabited geographic areas with lower household income ($87,500 versus $97,500; P < 0.001), larger household sizes, and higher proportions of people with education levels of secondary school or lower, as well as immigrants and visible minority groups (all P < 0.05). A total of 53.7% of seropositive individuals were potentially undetected cases with no prior positive COVID-19 nucleic acid test (NAAT). Antibodies were detectable in some patients up to 9 months post positive NAAT result. This seroprevalence study will continue to inform public health decisions by identifying at-risk demographics and geographical areas. IMPORTANCE Using SARS-CoV-2 serology testing, we assessed the proportion of people in Alberta, Canada (population 4.4 million) positive for COVID-19 antibodies, indicating previous infection, during the first two waves of the COVID-19 pandemic (prior to vaccination programs). Linking these results with sociodemographic population data provides valuable information as to which groups of the population are more likely to have been infected with the SARS-CoV-2 virus to help facilitate public health decision-making and interventions. We also compared seropositivity data with previous COVID-19 molecular testing results. Absence of antibody and molecular testing were highly correlated (95% negative concordance). Positive antibody correlation with a previous positive molecular test was low, suggesting the possibility of mild/asymptomatic infection or other reasons leading individuals from seeking medical attention. Our data highlight that the true estimate of population prevalence of COVID-19 is likely best informed by combining data from both serology and molecular testing.

Microbiol Spectr2021       LitCov and CORD-19
1002Comparison of the Clinical Course of COVID-19 Pneumonia and Acute Respiratory Distress Syndrome in 2 Passengers from the Cruise Ship Diamond Princess in February 2020  

Case series Patients: Male, 72-year-old • Male, 70-year-old Final Diagnosis: Acute respiratory distress syndrome (ARDS) • COVID-19 • COVID-19 pneumonia Symptoms: Cough • fever • malaise • nausea • respiratory distress • vomiting Medication: — Clinical Procedure: — Specialty: Critical Care Medicine • Infectious Diseases • Radiology OBJECTIVE: Rare disease BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome corona-virus 2 can rapidly progress to acute respiratory distress syndrome (ARDS). Because clinical diagnosis of ARDS includes several diseases, understanding the characteristics of COVID-19-related ARDS is necessary for precise treatment. We report 2 patients with ARDS due to COVID-19-associated pneumonia. CASE REPORT: Case 1 involved a 72-year-old Japanese man who presented with respiratory distress and fever. Computed tomography (CT) revealed subpleural ground-glass opacities (GGOs) and consolidation. Six days after symptom onset, reverse transcription-polymerase chain reaction (RT-PCR) testing confirmed the diagnosis of COVID-19-associated pneumonia. He was intubated and received veno-venous extracorporeal membrane oxygenation (ECMO) 8 days after symptom onset. Follow-up CT revealed large diffuse areas with a crazy-paving pattern and consolidation, which indicated progression of COVID-19-associated pneumonia. Following treatment with antiviral medications and supportive measures, the patient was weaned off ECMO after 20 days. Case 2 involved a 70-year-old Asian man residing in Canada who presented with cough, malaise, nausea, vomiting, and fever. COVID-19-associated pneumonia was diagnosed based on a positive result from RT-PCR testing. The patient was then transferred to the intensive care unit and intubated 8 days after symptom onset. Follow-up CT showed that while the initial subpleural GGOs had improved, diffuse GGOs appeared, similar to those observed upon diffuse alveolar damage. He was administered systemic steroid therapy for ARDS and extubated after 6 days. CONCLUSIONS: Because the pattern of symptom exacerbation in COVID-19-associated pneumonia cases seems inconsistent, individual treatment management, especially the CT-based treatment strategy, is crucial.

Am J Case Rep2020       LitCov and CORD-19
1003Effects of the COVID-19 Emergency and National Lockdown on Italian Citizens' Economic Concerns, Government Trust and Health Engagement: Evidence From a Two-Wave Panel Study  

POLICY POINTS: Preventive measures such as the national lockdown in Italy have been effective in slowing the spread of COVID‐19. However, they also had psychological and economic impacts on people’s lives, which should not be neglected as they may reduce citizens’ trust and compliance with future health mandates. Engaging citizens in their own health management and in the collaboration with health care professionals and authorities via the adoption of a collaborative approach to health policy development is fundamental to fostering such measures’ effectiveness. Psychosocial analysis of citizens’ concerns and emotional reactions to preventive policies is important in order to plan personalized health communication campaigns. CONTEXT: Because of the COVID‐19 pandemic, between February 23 and March 8, 2020, some areas of Italy were declared “red zones,” with citizens asked to stay home and avoid unnecessary interpersonal contacts. Such measures were then extended, between March 10 and May 4, 2020, to the whole country. However, compliance with such behaviors had an important impact on citizens’ personal, psychological, and economic well‐being. This could result in reduced trust in authorities and lowered compliance. Keeping citizens engaged in their own health and in preventive behaviors is thus a key strategy for the success of such measures. This paper presents the results from a study conducted in Italy to monitor levels of people’s health engagement, sentiment, trust in authorities, and perception of risk at two different time points. METHODS: Two independent samples (n = 968 and n = 1,004), weighted to be representative of the adult Italian population, were recruited in two waves corresponding to crucial moments of the Italian COVID‐19 epidemic: between February 28 and March 4 (beginning of “phase 1,” after the first regional lockdowns), and between May 12 and May 18 (beginning of “phase 2,” after the national lockdown was partially dismissed). Respondents were asked to complete an online survey with a series of both validated measures and ad hoc items. A series of t‐tests, general linear models, and contingency tables were carried out to assess if and how our measures changed over time in different social groups. FINDINGS: Although sense of self and social responsibility increased between the two waves, and trust toward authorities remained substantially the same, trust in science, consumer sentiment, and health engagement decreased. Our results showed that while both the level of general concern for the emergency and the perceived risk of infection increased between the two waves, in the second wave our participants reported being more concerned for the economic consequences of the pandemic than the health risk. CONCLUSIONS: The potentially disruptive psychological impact of lockdown may hamper citizens’ compliance with, and hence the effectiveness of, behavioral preventive measures. This suggests that preventive measures should be accompanied by collaborative educational plans aimed at promoting people’s health engagement by making citizens feel they are partners in the health preventive endeavor and involved in the development of health policies.

Milbank Q2021       LitCov and CORD-19
1004Effect of dexamethasone in patients with ARDS and COVID-19-prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate – PaO(2)/FiO(2) 100–200 mmHg; • Severe – PaO(2)/FiO(2) < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1–5, followed by dexamethasone 10 mg intravenously once daily on day 6–10. Patients in the control group will receive dexamethasone 6 mg day 1–10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05116-9.

Trials2021       LitCov and CORD-19
1005COVID-19: Coagulopathy, Risk of Thrombosis and the Rationale for Anticoagulation  

The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients. Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19. A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations. An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome. Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases. In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure. Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain. Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare. Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.

Clin Appl Thromb Hemost2020       LitCov and CORD-19
1006Intravenous vs inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery  

N/A

Cochrane Database Syst Rev2018       CORD-19
1007Visualization by immune electron microscopy of a 27-nm particle associated with acute infectious nonbacterial gastroenteritis  

N/A

J Virol1972       CORD-19
10086-month consequences of COVID-19 in patients discharged from hospital: a cohort study  

BACKGROUND: The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. METHODS: We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. FINDINGS: In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m(2) or more at acute phase had eGFR less than 90 mL/min per 1·73 m(2) at follow-up. INTERPRETATION: At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. FUNDING: National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.

Lancet2021       LitCov and CORD-19
1009Antibody response using six different serological assays in a completely PCR-tested community after a COVID-19 outbreak-the CoNAN study  

OBJECTIVES: Due to a substantial proportion of asymptomatic and mild courses, many SARS-CoV-2 infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed at determining and characterizing the rate of SARS-CoV-2 infections and the resulting seroprevalence in a defined population. The primary objective of the study was to assess SARS-CoV-2 antibody seroprevalence using six different IgG detecting immunoassays. Secondary objectives of the study were: i.) to determine potential risk factors for symptomatic vs. asymptomatic Covid19 courses; ii.) to investigate the rate of virus RNA-persistence. METHODS: CoNAN is a population-based cohort study performed in the community Neustadt am Rennsteig, Germany that was quarantined from March 22(nd) to April 5(th) after six SARS-CoV-2 cases were detected in the villages’ population. The SARS-CoV-2 outbreak compromised 51 cases and 3 deaths. The CoNAN study was performed from May 13th to May 22nd 2020 six weeks after a SARS-CoV-2 outbreak. RESULTS: We enrolled a total of 626 participants (71% of the community population) for PCR- and antibody testing in the study. All actual SARS-CoV-2 PCR tests were negative. Fifty-two out of 620 (8.4%) participants had antibodies against SARS-CoV-2 in at least two different assays. There were 38 participants with previously PCR-confirmed SARS-CoV-2 infection. Of those, only 19 (50%) displayed anti-SARS-CoV-2 antibodies. We also show that antibody positive participants with symptoms compatible with a respiratory tract infection had significantly higher antibody levels then asymptomatic participants (EU-assay: Median 2.9 vs. 7.2 IgG-index, p=0.002; DS-assay: Median 45.2 vs. 143 AU/mL, p=0.002). Persisting viral replication was not detected. CONCLUSIONS: Our data question the relevance and reliability of IgG antibody testing to detect past SARS-CoV-2 infections six weeks after an outbreak. We conclude that assessing immunity for SARS-CoV-2 infection should not only rely on antibody tests.

Clin Microbiol Infect2020       LitCov and CORD-19
1010Cytokine release syndrome in severe COVID-19  

N/A

Science2020       LitCov and CORD-19
1011Multi-tiered screening and diagnosis strategy for COVID-19: a model for sustainable testing capacity in response to pandemic  

Coronavirus disease 2019 (COVID-19), caused by novel enveloped single stranded RNA coronavirus (SARS-CoV-2), is responsible for an ongoing global pandemic. While other countries deployed widespread testing as an early mitigation strategy, the U.S. experienced delays in development and deployment of organism identification assays. As such, there is uncertainty surrounding disease burden and community spread, severely hampering containment efforts. COVID-19 illuminates the need for a tiered diagnostic approach to rapidly identify clinically significant infections and reduce disease spread. Without the ability to efficiently screen patients, hospitals are overwhelmed, potentially delaying treatment for other emergencies. A multi-tiered, diagnostic strategy incorporating a rapid host immune response assay as a screening test, molecular confirmatory testing and rapid IgM/IgG testing to assess benefit from quarantine/further testing and provide information on population exposure/herd immunity would efficiently evaluate potential COVID-19 patients. Triaging patients within minutes with a fingerstick rather than hours/days after an invasive swab is critical to pandemic response as reliance on the existing strategy is limited by assay accuracy, time to results, and testing capacity. Early screening and triage is achievable from the outset of a pandemic with point-of-care host immune response testing which will improve response time to clinical and public health actions. KEY MESSAGES: Delayed testing deployment has led to uncertainty surrounding overall disease burden and community spread, severely hampering public health containment and healthcare system preparation efforts. A multi-tiered testing strategy incorporating rapid, host immune point-of-care tests can be used now and for future pandemic planning by effectively identifying patients at risk of disease thereby facilitating quarantine earlier in the progression of the outbreak during the weeks and months it can take for pathogen specific confirmatory tests to be developed, validated and manufactured in sufficient quantities. The ability to triage patients at the point of care and support the guidance of medical and therapeutic decisions, for viral isolation or confirmatory testing or for appropriate treatment of COVID-19 and/or bacterial infections, is a critical component to our national pandemic response and there is an urgent need to implement the proposed strategy to combat the current outbreak.

Ann Med2020       LitCov and CORD-19
1012The SARS-CoV S glycoprotein: expression and functional characterization  

We have cloned, expressed, and characterized the full-length and various soluble fragments of the SARS-CoV (Tor2 isolate) S glycoprotein. Cells expressing S fused with receptor-expressing cells at neutral pH suggesting that the recombinant glycoprotein is functional, its membrane fusogenic activity does not require other viral proteins, and that low pH is not required for triggering membrane fusion; fusion was not observed at low receptor concentrations. S and its soluble ectodomain, S(e), were not cleaved to any significant degree. They ran at about 180–200 kDa in SDS gels suggesting post-translational modifications as predicted by previous computer analysis and observed for other coronaviruses. Fragments containing the N-terminal amino acid residues 17–537 and 272–537 but not 17–276 bound specifically to Vero E6 cells and purified soluble receptor, ACE2, recently identified by M. Farzan and co-workers [Nature 426 (2003) 450–454]. Together with data for inhibition of binding by antibodies developed against peptides from S, these findings suggest that the receptor-binding domain is located between amino acid residues 303 and 537. These results also confirm that ACE2 is a functional receptor for the SARS virus and may help in the elucidation of the mechanisms of SARS-CoV entry and in the development of vaccine immunogens and entry inhibitors.

Biochem Biophys Res Commun2003       CORD-19
1013Sex differences in immune responses  

N/A

Nat Rev Immunol2016       CORD-19
1014Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets  

Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.

mBio2020       LitCov and CORD-19
1015Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors  

Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors. We screened for psychiatric symptoms 402 adults surviving COVID-19 (265male,meanage58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels. A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil and platelet counts, positively associated with scores of depression and anxiety at follow-up. PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present obervation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.

Brain Behav Immun2020       LitCov and CORD-19
1016Attitudes and concerns of undergraduate university health sciences students in Croatia regarding complete switch to e-learning during COVID-19 pandemic: a survey  

BACKGROUND: Croatia has closed all educational institutions after 32 cases of SARS-CoV-2 infection were confirmed and switched to exclusive e-learning. Health sciences university students may have been particularly affected with this change due to a lack of practical education. It is not known how health sciences students and schools have adjusted to exclusive e-learning. This study aimed to explore attitudes and concerns of health sciences students in Croatia regarding the complete switch to e-learning during the COVID-19 pandemic. METHODS: Eligible participants were students from 9 institutions offering university-level health sciences education in Croatia enrolled in the academic year 2019/2010, and participating in e-learning. Data were collected with a questionnaire distributed via email during April/May 2020. RESULTS: A total of 2520 students (aged 25.7 ± 7.7 years) responded to the questionnaire (70.3% response rate). General satisfaction with exclusive e-learning was rated with average grade of 3.7 out of 5. Compared with previous education, exclusive e-learning was rated with average grade of 3.2 out of 5. Compared to classroom learning, equal or higher motivation to attend exclusive e-learning was reported by 64.4% of participants. With a longer duration of exclusive e-learning, equal or higher motivation was reported by 65.5% of participants. Less than half of the students indicated they felt deprived or concerned due to the lack of practical lessons. Most participants indicated that in the future, they would prefer to combine classic classroom and e-learning (N = 1403; 55.7%). CONCLUSIONS: Most health sciences students were satisfied with the exclusive e-learning, as well as their personal and institutional adjustment to it. Students’ feedback can help institutions to improve the exclusive e-learning experience for students in the time of the pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12909-020-02343-7.

BMC Med Educ2020       LitCov and CORD-19
1017Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young  

N Engl J Med2020       LitCov and CORD-19
1018Psychological stress and susceptibility to the common cold  

N/A

N Engl J Med1991       CORD-19
1019Use of Telemedicine and Virtual Care for Remote Treatment in Response to COVID-19 Pandemic  

The current coronavirus disease 2019 (COVID-19) pandemic has caused significant strain on medical centers resources. Thus, concerns about the reducing and management of COVID-19 are on the rise, as there is need to provide diagnosis, treatment, monitoring, and follow-ups during the pandemic. Therefore, the COVID-19 pandemic has radically and quickly altered how medical practitioners provide care to patients. Medical centers are now responding to COVID-19 through rapid adoption of digital tools and technologies such as telemedicine and virtual care which refer to the delivery of healthcare services digital or at a distance using Information and Communications Technology (ICT) for treatment of patients. Telemedicine is expected to deliver timely care while minimizing exposure to protect medical practitioners and patients. Accordingly, a rapid literature review was conducted, and 35 research studies published from 2019 to May 2020 were employed to provide theoretical and practical evidence on the significance of using telemedicine and virtual care for remote treatment of patients during the COVID-19 pandemic. This article provides practical guide based on how to use telemedicine and virtual care during the COVID-19 pandemic. This study provides implication on the potentials of consolidating virtual care solutions in the near future towards contributing to integrate digital technologies into healthcare.

J Med Syst2020       LitCov and CORD-19
1020Factors Associated with a Positive SARS-CoV-2 Testing in Suspected Cases Presenting with Pneumonia: A Retrospective Cohort Study in a Single Medical Center  

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Respiration2020       LitCov and CORD-19
1021The First International Consensus Summit for Sleeve Gastrectomy (SG), New York City, October 25-27, 2007  

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Obes Surg2008       CORD-19
1022Psychological health during the COVID-19 pandemic outbreak  

BACKGROUND: The current ongoing pandemic outbreak of COVID-19 (Coronavirus Disease 2019) has globally affected 213 countries and territories with more than 2.5 million confirmed cases and thousands of casualties. The unpredictable and uncertain COVID-19 outbreak has the potential of adversely affecting the psychological health on individual and community level. Currently all efforts are focused on the understanding of epidemiology, clinical features, mode of transmission, counteract the spread of the virus, and challenges of global health, while crucially significant mental health has been overlooked in this endeavor. METHOD: This review is to evaluate past outbreaks to understand the extent of adverse effects on psychological health, psychological crisis intervention, and mental health management plans. Published previous and current articles on PubMed, EMBASE, Google Scholar, and Elsevier about psychological impact of infectious diseases outbreaks and COVID-19 has been considered and reviewed. COMMENTS: COVID-19 is leading to intense psychosocial issues and comprising mental health marking a secondary health concern all around the world. Globally implementing preventive and controlling measures, and cultivating coping and resilience are challenging factors; modified lifestyle (lockdown curfew, self-isolation, social distancing and quarantine); conspiracy theories, misinformation and disinformation about the origin, scale, signs, symptoms, transmission, prevention and treatment; global socioeconomic crisis; travel restrictions; workplace hazard control; postponement and cancellation of religious, sports, cultural and entertainment events; panic buying and hoarding; incidents of racism, xenophobia, discrimination, stigma, psychological pressure of productivity, marginalization and violence; overwhelmed medical centers and health organizations, and general impact on education, politics, socioeconomic, culture, environment and climate – are some of the risk factors to aggravate further problems.

Int J Soc Psychiatry2020       LitCov and CORD-19
1023Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19  

OBJECTIVE: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents. METHOD: For this rapid review, we searched MEDLINE, PSYCHINFO, and Web of Science for articles published between 01/01/1946 and 03/29/2020. 20% of articles were double screened using pre-defined criteria and 20% of data was double extracted for quality assurance. RESULTS: 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n=51,576; mean age 15.3) 61 studies were observational; 18 were longitudinal and 43 cross sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time loneliness was measured and between 0.25 to 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness. CONCLUSION: Children and adolescents are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventative support and early intervention where possible and be prepared for an increase in mental health problems.

J Am Acad Child Adolesc Psychi2020       LitCov and CORD-19
1024Epidemiology, Genetic Recombination and Pathogenesis of Coronaviruses  

Human coronaviruses (HCoVs) were first described in the 1960s for patients with the common cold. Since then, more HCoVs have been discovered, including those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), two pathogens that, upon infection, can cause fatal respiratory disease in humans. It was recently discovered that dromedary camels in Saudi Arabia harbor three different HCoV species, including a dominant MERS HCoV lineage that was responsible for the outbreaks in the Middle East and South Korea during 2015. In this review we aim to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans.

Trends Microbiol2016       CORD-19
1025Preliminary CT findings of COVID-19  

OBJECTIVES: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This paper aims to examine the CT imaging characteristics of COVID-19. METHODS: We evaluated CT images obtained between 10 January 2019 and 16 February 2020 at Taihe Hospital. Scans were conducted 2–6 times per patient and the re-testing interval was 2–7 days. Ninety-five patients with positive SARS-CoV-2 nucleic acid test results were included in this study and we retrospectively analysed their CT imaging characteristics. RESULTS: Ninety-five patients underwent 2–3 SARS-CoV-2 nucleic acid tests and received a definitive diagnosis of COVID-19. Fifty-three were male and 42 were female, and their mean age was 42 ± 12 years (range: 10 months to 81 years). Sixty-nine patients (72.6%) experienced fever, fatigue, and dry cough, while 15 (15.8%) had poor appetite and fatigue, and 11 (11.6%) had a dry cough and no fever. On CT imaging, early stage patients (n = 53, 55.8%) showed peripheral subpleural ground-glass opacities; these were mainly local patches (22/53, 41.5%), while some lesions were accompanied by interlobular septal thickening. Thirty-four (35.8%) patients were classified in the ‘progression stage’ based on CT imaging; these patients typically showed lesions in multiple lung segments and lobes (21/34,61.8%), and an uneven increase in ground-glass opacity density accompanied by consolidation and grid-like or cord-like shadows(30.5%). Two patients (2.1%) showed a severe presentation on CT. These showed diffuse bilateral lung lesions, mixed ground-glass opacities and consolidation with cord-like interstitial thickening and air bronchograms, entire lung involvement with a “white lung” presentation, and mild pleural effusion. Six patients in remission (6.3%), visible lesion absorption, fibrotic lesions. Based on clinical signs, 71 (74.7%), 22 (23.2%), and 2 (2.1%) patients had mild or moderate, severe, and critical disease, respectively. Within the follow-up period, 93 patients recovered and were discharged, including the 53 early stage patients and 34 progression stage patients. The length of hospitalisation was 7–28 days (mean: 10 ± 3.5 days). On discharge, lesions were significantly reduced in area and had in many cases completely disappeared, while slight pulmonary fibrosis was present in some patients. One severe stage patient was still hospitalised at the end of the follow-up period and the other severe stage patient died. The overall mortality rate was 1.05%. CONCLUSIONS: Understanding the CT imaging characteristics of COVID-19 is important for early lesion detection, determining the nature of lesions, and assessing disease severity.

Clin Imaging2020       LitCov and CORD-19
1026Perception and attitude of healthcare workers in Saudi Arabia with regard to Covid-19 pandemic and potential associated predictors  

BACKGROUND: Healthcare workers (HCWs) face considerable mental and physical stress caring for patients with Covid-19. They are at higher risk of acquiring and transmitting this virus. This study aims to assess perception and attitude of HCWs in Saudi Arabia with regard to Covid-19, and to identify potential associated predictors. METHODS: In a cross-sectional study, HCWs at three tertiary hospitals in Saudi Arabia were surveyed via email with an anonymous link, by a concern scale about Covid-19 pandemic during 15–30 April, 2020. Concerns of disease severity, governmental efforts to contain it and disease outcomes were assessed using 32 concern statements in five distinct domains. Multiple regression analysis was used to identify predictors of high concern scores. RESULTS: A total of 844 HCW responded to the survey. Their average age was 40.4 ± 9.5 years, 40.3% were nurses, 58.2% had direct patient contact, and 77.3% were living with others. The majority of participants (72.1%) had overall concern scores of 55 or less out of a maximum score of 96 points, with an overall mean score of 48.5 ± 12.8 reflecting moderate level of concern. Three-fourth of respondents felt at risk of contracting Covid-19 infection at work, 69.1% felt threatened if a colleague contracted Covid-19, 69.9% felt obliged to care for patients infected with Covid-19 while 27.7% did not feel safe at work using the standard precautions available. Nearly all HCWs believed that the government should isolate patients with Covid-19 in specialized hospitals (92.9%), agreed with travel restriction to and/or from areas affected by Covid-19 (94.7%) and felt safe the government implemented curfew and movement restriction periods (93.6%). Predictors of high concern scores were; HCWs of Saudi nationality (p < 0.001), younger age (p = 0.003), undergraduate education (p = 0.044), living with others (p = 0.003) working in the western region (p = 0.003) and direct contact with patients (p = 0.018). CONCLUSIONS: This study highlights the high concern among HCWs about Covid-19 and identifies the predictors of those with highest concern levels. To minimize the potential negative impact of those concerns on the performance of HCWs during pandemics, measures are necessary to enhance their protection and to minimize the psychological effect of the perceived risk of infection.

BMC Infect Dis2020       LitCov and CORD-19
1027coinfections among patients with COVID-19: The need for combination therapy with non-anti-SARS-CoV-2 agents?  

Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.

J Microbiol Immunol Infect2020       LitCov and CORD-19
1028Artificial Intelligence Distinguishes COVID-19 from Community Acquired Pneumonia on Chest CT  

BACKGROUND: Coronavirus disease has widely spread all over the world since the beginning of 2020. It is desirable to develop automatic and accurate detection of COVID-19 using chest CT. PURPOSE: To develop a fully automatic framework to detect COVID-19 using chest CT and evaluate its performances. MATERIALS AND METHODS: In this retrospective and multi-center study, a deep learning model, COVID-19 detection neural network (COVNet), was developed to extract visual features from volumetric chest CT exams for the detection of COVID-19. Community acquired pneumonia (CAP) and other non-pneumonia CT exams were included to test the robustness of the model. The datasets were collected from 6 hospitals between August 2016 and February 2020. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS: The collected dataset consisted of 4356 chest CT exams from 3,322 patients. The average age is 49±15 years and there were slightly more male patients than female (1838 vs 1484; p-value=0.29). The per-exam sensitivity and specificity for detecting COVID-19 in the independent test set was 114 of 127 (90% [95% CI: 83%, 94%]) and 294 of 307 (96% [95% CI: 93%, 98%]), respectively, with an AUC of 0.96 (p-value<0.001). The per-exam sensitivity and specificity for detecting CAP in the independent test set was 87% (152 of 175) and 92% (239 of 259), respectively, with an AUC of 0.95 (95% CI: 0.93, 0.97). CONCLUSIONS: A deep learning model can accurately detect COVID-19 and differentiate it from community acquired pneumonia and other lung diseases.

Radiology2020       LitCov and CORD-19
1029Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan  

Abstract Background In December 2019, COVID-19 outbreak occurred in Wuhan. Data on the clinical characteristics and outcomes of patients with severe COVID-19 are limited. Objective The severity on admission, complications, treatment, and outcomes of COVID-19 patients were evaluated. Methods Patients with COVID-19 admitted to Tongji Hospital from January 26, 2020 to February 5, 2020 were retrospectively enrolled and followed-up until March 3, 2020. Potential risk factors for severe COVID-19 were analyzed by a multivariable binary logistic model. Cox proportional hazard regression model was used for survival analysis in severe patients. Results We identified 269 (49.1%) of 548 patients as severe cases on admission. Elder age, underlying hypertension, high cytokine levels (IL-2R, IL-6, IL-10, and TNF-a), and high LDH level were significantly associated with severe COVID-19 on admission. The prevalence of asthma in COVID-19 patients was 0.9%, markedly lower than that in the adult population of Wuhan. The estimated mortality was 1.1% in nonsevere patients and 32.5% in severe cases during the average 32 days of follow-up period. Survival analysis revealed that male, elder age, leukocytosis, high LDH level, cardiac injury, hyperglycemia, and high-dose corticosteroid use were associated with death in patients with severe COVID-19. Conclusions Patients with elder age, hypertension, and high LDH level need careful observation and early intervention to prevent the potential development of severe COVID-19. Severe male patients with heart injury, hyperglycemia, and high-dose corticosteroid use may have high risk of death.

J Allergy Clin Immunol2020       LitCov and CORD-19
1030Natural cytotoxicity against mouse hepatitis virus-infected target cells. I. Correlation of cytotoxicity with virus binding to leukocytes  

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J Immunol1986       CORD-19
1031Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults  

BACKGROUND: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. METHODS: We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. RESULTS: Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. CONCLUSIONS: In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.)

N Engl J Med2020       LitCov and CORD-19
1032Infection Prevention Precautions for Routine Anesthesia Care During the SARS-CoV-2 Pandemic  

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Anesth Analg2020       LitCov and CORD-19
1033Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group  

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J Virol2013       CORD-19
1034Influenza  

Although most influenza infections are self-limited, few other diseases exert such a huge toll of suffering and economic loss. Despite the importance of influenza, there had been, until recently, little advance in its control since amantadine was licensed almost 40 years ago. During the past decade, evidence has accrued on the protection afforded by inactivated vaccines and the safety and efficacy in children of live influenza-virus vaccines. There have been many new developments in vaccine technology. Moreover, work on viral neuraminidase has led to the licensing of potent selective antiviral drugs, and economic decision modelling provides further justification for annual vaccination and a framework for the use of neuraminidase inhibitors. Progress has also been made on developing near-patient testing for influenza that may assist individual diagnosis or the recognition of widespread virus circulation, and so optimise clinical management. Despite these advances, the occurrence of avian H5N1, H9N2, and H7N7 influenza in human beings and the rapid global spread of severe acute respiratory syndrome are reminders of our vulnerability to an emerging pandemic. The contrast between recent cases of H5N1 infection, associated with high mortality, and the typically mild, self-limiting nature of human infections with avian H7N7 and H9N2 influenza shows the gaps in our understanding of molecular correlates of pathogenicity and underlines the need for continuing international research into pandemic influenza. Improvements in animal and human surveillance, new approaches to vaccination, and increasing use of vaccines and antiviral drugs to combat annual influenza outbreaks are essential to reduce the global toll of pandemic and interpandemic influenza.

Lancet2003       CORD-19
1035High-flow nasal cannulae for respiratory support in adult intensive care patients  

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Cochrane Database Syst Rev2017       CORD-19
1036The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance  

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JAMA2020       LitCov and CORD-19
1037A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)  

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Mil Med Res2020       LitCov and CORD-19
1038Caregiver willingness to vaccinate their children against COVID-19: Cross sectional survey  

Background More than 100 COVID-19 vaccine candidates are in development since the SARS-CoV-2 genetic sequence was published in January 2020. The uptake of a COVID-19 vaccine among children will be instrumental in limiting the spread of the disease as herd immunity may require vaccine coverage of up to 80% of the population. Prior history of pandemic vaccine coverage was as low as 40% among children in the United States during the 2009 H1N1 influenza pandemic. Purpose To investigate predictors associated with global caregivers’ intent to vaccinate their children against COVID-19, when the vaccine becomes available. Method An international cross sectional survey of 1541 caregivers arriving with their children to 16 pediatric Emergency Departments (ED) across six countries from March 26 to May 31, 2020. Results 65% (n = 1005) of caregivers reported that they intend to vaccinate their child against COVID-19, once a vaccine is available. A univariate and subsequent multivariate analysis found that increased intended uptake was associated with children that were older, children with no chronic illness, when fathers completed the survey, children up-to-date on their vaccination schedule, recent history of vaccination against influenza, and caregivers concerned their child had COVID-19 at the time of survey completion in the ED. The most common reason reported by caregivers intending to vaccinate was to protect their child (62%), and the most common reason reported by caregivers refusing vaccination was the vaccine’s novelty (52%). Conclusions The majority of caregivers intend to vaccinate their children against COVID-19, though uptake will likely be associated with specific factors such as child and caregiver demographics and vaccination history. Public health strategies need to address barriers to uptake by providing evidence about an upcoming COVID-19 vaccine’s safety and efficacy, highlighting the risks and consequences of infection in children, and educating caregivers on the role of vaccination.

Vaccine2020       LitCov and CORD-19
1039Monitoring community responses to the SARS epidemic in Hong Kong: from day 10 to day 62  

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J Epidemiol Community Health2003       CORD-19
1040Measures implemented in the school setting to contain the COVID-19 pandemic  

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Cochrane Database Syst Rev2022       LitCov and CORD-19
1041Aerosol Generating Procedures and Risk of Transmission of Acute Respiratory Infections to Healthcare Workers: A Systematic Review  

Aerosol generating procedures (AGPs) may expose health care workers (HCWs) to pathogens causing acute respiratory infections (ARIs), but the risk of transmission of ARIs from AGPs is not fully known. We sought to determine the clinical evidence for the risk of transmission of ARIs to HCWs caring for patients undergoing AGPs compared with the risk of transmission to HCWs caring for patients not undergoing AGPs. We searched PubMed, EMBASE, MEDLINE, CINAHL, the Cochrane Library, University of York CRD databases, EuroScan, LILACS, Indian Medlars, Index Medicus for SE Asia, international health technology agencies and the Internet in all languages for articles from 01/01/1990 to 22/10/2010. Independent reviewers screened abstracts using pre-defined criteria, obtained full-text articles, selected relevant studies, and abstracted data. Disagreements were resolved by consensus. The outcome of interest was risk of ARI transmission. The quality of evidence was rated using the GRADE system. We identified 5 case-control and 5 retrospective cohort studies which evaluated transmission of SARS to HCWs. Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)] tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)], non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)], tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] and manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]. Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. Our findings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.

PLoS One2012       CORD-19
1042DNA vaccine protection against SARS-CoV-2 in rhesus macaques  

The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.

Science2020       LitCov and CORD-19
1043Identification of Novel Small-Molecule Inhibitors of Severe Acute Respiratory Syndrome-Associated Coronavirus by Chemical Genetics  

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (M(pro)), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC(50) of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV M(pro), Hel, and viral entry, respectively, exhibited potent antiviral activity (EC(50) < 10 μM) and comparable inhibitory activities in target-specific in vitro assays.

Chem Biol2004       CORD-19
1044Public health awareness of emerging zoonotic viruses of bats: a European perspective  

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Vector Borne Zoonotic Dis2006       CORD-19
1045SARS-CoV-2 Infection in Children  

N Engl J Med2020       LitCov and CORD-19
1046Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis  

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BMJ2003       CORD-19
1047SARS: Systematic Review of Treatment Effects  

BACKGROUND: The SARS outbreak of 2002–2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.

PLoS Med2006       CORD-19
1048Coronavirus Replication Complex Formation Utilizes Components of Cellular Autophagy  

The coronavirus mouse hepatitis virus (MHV) performs RNA replication on double membrane vesicles (DMVs) in the cytoplasm of the host cell. However, the mechanism by which these DMVs form has not been determined. Using genetic, biochemical, and cell imaging approaches, the role of autophagy in DMV formation and MHV replication was investigated. The results demonstrated that replication complexes co-localize with the autophagy proteins, microtubule-associated protein light-chain 3 and Apg12. MHV infection induces autophagy by a mechanism that is resistant to 3-methyladenine inhibition. MHV replication is impaired in autophagy knockout, APG5–/–, embryonic stem cell lines, but wild-type levels of MHV replication are restored by expression of Apg5 in the APG5–/–cells. In MHV-infected APG5–/–cells, DMVs were not detected; rather, the rough endoplasmic reticulum was dramatically swollen. The results of this study suggest that autophagy is required for formation of double membrane-bound MHV replication complexes and that DMV formation significantly enhances the efficiency of replication. Furthermore, the rough endoplasmic reticulum is implicated as the possible source of membranes for replication complexes.

J Biol Chem2004       CORD-19
1049Risk factors for COVID-19 among healthcare workers. A protocol for a systematic review and meta-analysis  

BACKGROUND: Evidence on the spectrum of risk factors for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among front-line healthcare workers (HCWs) has not been well-described. While several studies evaluating the risk factors associated with SARS-CoV-2 infection among patient-facing and non-patient-facing front-line HCWs have been reported since the outbreak of the coronavirus disease in 2019 (COVID-19), and several more are still underway. There is, therefore, an immediate need for an ongoing, rigorous systematic review that continuously assesses the risk factors of SARS-CoV-2 infection among front-line HCWs. OBJECTIVE: Here, we outline a protocol to serve as a guideline for conducting a living systematic review and meta-analysis to examine the burden of COVID-19 on front-line HCWs and identify risk factors for SARS-CoV-2 infection in patient-facing and non-patient-facing front-line HCWs. METHODS: The protocol was developed and reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The conduct of the proposed living systematic review and meta-analysis will primarily follow the principles recommended in the Centre for Reviews and Dissemination (CRD) guidance for undertaking systematic reviews in healthcare, and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The systematic literature searches will be performed using the EBSCOhost platform by searching the following databases within the platform: Academic search complete, health source: nursing/academic edition, CINAHL with full text, Embase, PubMed, MEDLINE, Science Direct databases, Google Scholar, and; also a search in the China National Knowledge Infrastructure and the World Health Organization library databases for relevant studies will be performed. The searches will include peer-reviewed articles, published in English and Mandarin language irrespective of publication year, evaluating the risk for testing positive for C0VID-19, the risk of developing symptoms associated with SARS-CoV-2 infection, or both, among front-line HCWs. The initial review period will consider articles published since the onset of COVID-19 disease to the present and then updated monthly. Review Manager (RevMan 5.3) will be used to pool the odds ratios or mean differences for individual risk factors where possible. Results will be presented as relative risks and 95% confidence intervals for dichotomous outcomes and mean differences, or standardised mean differences along with 95% confidence intervals, for continuous outcomes. The Newcastle–Ottawa Scale will be used to rate study quality, and the certainty of the evidence will be assessed by using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). The results of the living systematic review and meta-analysis will be reported per the PRISMA guidelines. DISCUSSION: Though addressing the needs of front-line HCWs during the COVID-19 pandemic is a high priority, data to inform such initiatives are inadequate, particularly data on the risk factor disparities between patient-facing and non-patient-facing front-line HCWs. The proposed living systematic review and meta-analysis anticipate finding relevant studies reporting risk factors driving the SARS-CoV-2 infection rates among patient-facing and non-patient-facing front-line HCWs, thus providing subsidies for public health interventions and occupational health policies. The study results will be disseminated electronically, in print and through conference presentation, and key stakeholder meetings in the form of policy briefs. TRAIL REGISTRATION: PROSPERO registration number: CRD42020193508 available for public comments via the link below https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193508).

PLoS One2021       LitCov and CORD-19
1050Antibody Detection and Dynamic Characteristics in Patients with COVID-19  

BACKGROUND: The corona virus disease 2019 (COVID-19) caused by the corona virus 2 (SARS-CoV-2) has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay (ELISA) based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by RT-PCR. The serodiagnostic power of the specific IgM and IgG antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the 4(th) day after symptom onset. In the confirmed patients with COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, and those of IgG were 83.3.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9 %. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stage of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as complement approach for viral nucleid acid assays.

Clin Infect Dis2020       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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