\ 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
301COVID-19 and lombardy: TESTing the impact of the first wave of the pandemic  

BACKGROUND: Italy was the first western country to experience a large Coronavirus Disease 2019 (COVID-19) outbreak and the province of Bergamo experienced one of the deadliest COVID-19 outbreaks in the world. Following the peak of the epidemic in mid-March, the curve has slowly fallen thanks to the strict lockdown imposed by the Italian government on 9th March 2020. METHODS: We performed a cross-sectional study to assess the prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in 423 workers in Bergamo province who returned to the workplace after the end of the Italian lockdown on 5th May 2020. To this end, we performed an enzyme-linked immunosorbent assay (ELISA) to detect the humoral response against SARS-CoV-2 and a nasopharyngeal swab to assess the presence of SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR). As a secondary aim of the study, we validated a lateral flow immunochromatography assay (LFIA) for the detection of anti-SARS-CoV-2 antibodies. FINDINGS: ELISA identified 38.5% positive subjects, of whom 51.5% were positive for both IgG and IgM, 47.3% were positive only for IgG, but only 1.2% were positive for IgM alone. Only 23 (5.4%) participants tested positive for SARS-CoV-2 by rRT-PCR, although with high cycle thresholds (between 34 and 39), indicating a very low residual viral load that was not able to infect cultured cells. All these rRT-PCR positive subjects had already experienced seroconversion. When the ELISA was used as the comparator, the estimated specificity and sensitivity of the rapid LFIA for IgG were 98% and 92%, respectively. INTERPRETATION: the prevalence of SARS-CoV-2 infection in the province of Bergamo reached 38.5%, significantly higher than has been reported for most other regions worldwide. Few nasopharyngeal swabs tested positive in fully recovered subjects, though with a very low SARS-CoV-2 viral load, with implications for infectivity and discharge policies for positive individuals in the post-pandemic period. The rapid LFIA used in this study is a valuable tool for rapid serologic surveillance of COVID-19 for population studies. FUNDING: The study was supported by Regione Lombardia, Milano Serravalle - Milano Tangenziali S.p.A., Brembo S.p.A, and by MEI System.

EBioMedicine2020       LitCov and CORD-19
302Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial  

BACKGROUND: The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans. METHODS: We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18–80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18–59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 μg, 4 μg, or 8 μg on days 0 and 28. In phase 2, healthy adults (aged 18–59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 μg on day 0 or on a two-dose schedule of 4 μg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459. FINDINGS: In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 μg [n=24], 4 μg [n=24], or 8 μg [n=24] for both age groups [18–59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18–59 years, one [4%] in the 2 μg group, one [4%] in the 4 μg group, and two [8%] in the 8 μg group; ≥60 years, one [4%] in the 8 μg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18–59 years (87·7 [95% CI 64·9–118·6], 2 μg group; 211·2 [158·9–280·6], 4 μg group; and 228·7 [186·1–281·1], 8 μg group) and the group aged 60 years and older (80·7 [65·4–99·6], 2 μg group; 131·5 [108·2–159·7], 4 μg group; and 170·87 [133·0–219·5], 8 μg group) compared with the placebo group (2·0 [2·0–2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 μg on day 0 [n=84] or 4 μg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 μg day 0; 18 [21%], 4 μg days 0 and 14; 15 [18%], 4 μg days 0 and 21; and ten [12%], 4 μg days 0 and 28). One placebo recipient in the 4 μg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 μg day 0; one [1%], 4 μg days 0 and 14; three [4%], 4 μg days 0 and 21; two [2%], 4 μg days 0 and 28). The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 μg days 0 and 14 (169·5, 95% CI 132·2–217·1), days 0 and 21 (282·7, 221·2–361·4), and days 0 and 28 (218·0, 181·8–261·3) schedules than the 8 μg day 0 schedule (14·7, 11·6–18·8; all p<0·001). INTERPRETATION: The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 μg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 μg dose or 4 μg dose on days 0 and 14. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

Lancet Infect Dis2020       LitCov and CORD-19
303Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicenter trial  

Summary Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.

Lancet2020       LitCov and CORD-19
304Using social and behavioural science to support COVID-19 pandemic response  

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Nat Hum Behav2020       LitCov and CORD-19
305Pathophysiology, Transmission, Diagnosis and Treatment of COVID-19: A Review  

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JAMA2020       LitCov and CORD-19
306Asymptomatic carrier state, acute respiratory disease and pneumonia due to SARS-CoV-2: Facts and myths  

Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

J Microbiol Immunol Infect2020       LitCov and CORD-19
307Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome  

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JAMA2003       CORD-19
308Reviewing and Reflecting on Nursing During the COVID-19 Pandemic  

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Hu Li Za Zhi2020       LitCov and CORD-19
309The Psychological Experience of Obstetric Patients and Healthcare Workers after Implementation of Universal SARS-CoV-2 Testing  

Objective This study was aimed to describe the hospitalization and early postpartum psychological experience for asymptomatic obstetric patients tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) as part of a universal testing program and report the impact of this program on labor and delivery health care workers' job satisfaction and workplace anxiety. Study Design This is a cohort study of asymptomatic pregnant women who underwent SARS-CoV-2 testing between April 13, 2020 and April 26, 2020. Semistructured interviews were conducted via telephone at 1 and 2 weeks posthospitalization to assess maternal mental health. Depression screening was conducted using the patient health questionnaire-2 (PHQ-2). An online survey of labor and delivery health care workers assessed job satisfaction and job-related anxiety before and during the novel coronavirus disease 2019 (COVID-19) pandemic, as well as employees' subjective experience with universal testing. Patient and employee responses were analyzed for recurring themes. Results A total of 318 asymptomatic women underwent SARS-CoV-2 testing during this 2-week period. Six of the eight women (75%) who tested positive reported negative in-hospital experiences secondary to perceived lack of provider and partner support and neonatal separation after birth. Among the 310 women who tested negative, 34.4% of multiparous women reported increased postpartum anxiety compared with their prior deliveries due to concerns about infectious exposure in the hospital and lack of social support. Only 27.6% of women, tested negative, found their test result to be reassuring. Job satisfaction and job-related anxiety among health care workers were negatively affected. Universal testing was viewed favorably by the majority of health care workers despite concerns about delays or alterations in patient care and maternal and neonatal separation. Conclusion Universal testing for SARS-CoV-2 in obstetric units has mixed effects on maternal mental health but is viewed favorably by labor and delivery employees. Ongoing evaluation of new testing protocols is paramount to balance staff and patient safety with quality and equality of care. Key Points: Women with SARS-CoV-2 had a negative hospital experience. A negative SARS-CoV-2 test was not reassuring for patients. COVID-19 negatively impacts healthcare workers’ well-being.

Am J Perinatol2020       LitCov and CORD-19
310Reply to Letter to the Editor, Reply to Yasri & Wiwanitkit  

Endoscopy2020       LitCov and CORD-19
311Cardiac Involvement in a Patient With COVID-19  

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JAMA Cardiol2020       LitCov and CORD-19
312Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor  

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Nature2020       LitCov and CORD-19
313Physical distancing, face masks and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and is spread person-to-person through close contact. We aimed to investigate the effects of physical distance, face masks, and eye protection on virus transmission in health-care and non-health-care (eg, community) settings. METHODS: We did a systematic review and meta-analysis to investigate the optimum distance for avoiding person-to-person virus transmission and to assess the use of face masks and eye protection to prevent transmission of viruses. We obtained data for SARS-CoV-2 and the betacoronaviruses that cause severe acute respiratory syndrome, and Middle East respiratory syndrome from 21 standard WHO-specific and COVID-19-specific sources. We searched these data sources from database inception to May 3, 2020, with no restriction by language, for comparative studies and for contextual factors of acceptability, feasibility, resource use, and equity. We screened records, extracted data, and assessed risk of bias in duplicate. We did frequentist and Bayesian meta-analyses and random-effects meta-regressions. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. This study is registered with PROSPERO, CRD42020177047. FINDINGS: Our search identified 172 observational studies across 16 countries and six continents, with no randomised controlled trials and 44 relevant comparative studies in health-care and non-health-care settings (n=25 697 patients). Transmission of viruses was lower with physical distancing of 1 m or more, compared with a distance of less than 1 m (n=10 736, pooled adjusted odds ratio [aOR] 0·18, 95% CI 0·09 to 0·38; risk difference [RD] −10·2%, 95% CI −11·5 to −7·5; moderate certainty); protection was increased as distance was lengthened (change in relative risk [RR] 2·02 per m; p(interaction)=0·041; moderate certainty). Face mask use could result in a large reduction in risk of infection (n=2647; aOR 0·15, 95% CI 0·07 to 0·34, RD −14·3%, −15·9 to −10·7; low certainty), with stronger associations with N95 or similar respirators compared with disposable surgical masks or similar (eg, reusable 12–16-layer cotton masks; p(interaction)=0·090; posterior probability >95%, low certainty). Eye protection also was associated with less infection (n=3713; aOR 0·22, 95% CI 0·12 to 0·39, RD −10·6%, 95% CI −12·5 to −7·7; low certainty). Unadjusted studies and subgroup and sensitivity analyses showed similar findings. INTERPRETATION: The findings of this systematic review and meta-analysis support physical distancing of 1 m or more and provide quantitative estimates for models and contact tracing to inform policy. Optimum use of face masks, respirators, and eye protection in public and health-care settings should be informed by these findings and contextual factors. Robust randomised trials are needed to better inform the evidence for these interventions, but this systematic appraisal of currently best available evidence might inform interim guidance. FUNDING: World Health Organization.

Lancet2020       LitCov and CORD-19
314Origin and evolution of pathogenic coronaviruses  

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.

Nat Rev Microbiol2018       CORD-19
315Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines  

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of “disease enhancement” has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory Syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.

Vaccine2020       LitCov and CORD-19
316Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration  

The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.

Elife2020       LitCov and CORD-19
317Psychological impact of COVID-19 pandemic in the Philippines  

BACKGROUND: : The 2019 coronavirus disease (COVID-19) pandemic poses a threat to societies’ mental health. This study examined the prevalence of psychiatric symptoms and identified the factors contributing to psychological impact in the Philippines. METHODS: : A total of 1879 completed online surveys were gathered from March 28-April 12, 2020. Collected data included socio-demographics, health status, contact history, COVID-19 knowledge and concerns, precautionary measures, information needs, the Depression, Anxiety and Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) ratings. RESULTS: : The IES-R mean score was 19.57 (SD=13.12) while the DASS-21 mean score was 25.94 (SD=20.59). In total, 16.3% of respondents rated the psychological impact of the outbreak as moderate-to-severe; 16.9% reported moderate-to-severe depressive symptoms; 28.8% had moderate-to-severe anxiety levels; and 13.4% had moderate-to-severe stress levels. Female gender; youth age; single status; students; specific symptoms; recent imposed quarantine; prolonged home-stay; and reports of poor health status, unnecessary worry, concerns for family members, and discrimination were significantly associated with greater psychological impact of the pandemic and higher levels of stress, anxiety and depression (p<0.05). Adequate health information, having grown-up children, perception of good health status and confidence in doctors’ abilities were significantly associated with lesser psychological impact of the pandemic and lower levels of stress, anxiety and depression (p<0.05). LIMITATIONS: : An English online survey was used. CONCLUSION: : During the early phase of the pandemic in the Philippines, one-fourth of respondents reported moderate-to-severe anxiety and one-sixth reported moderate-to-severe depression and psychological impact. The factors identified can be used to devise effective psychological support strategies.

J Affect Disord2020       LitCov and CORD-19
318The Influence of Coronavirus Diseases 2019 Pandemic and the Quarantine Practices on University Students' Beliefs About the Online Learning Experience in Jordan  

Coronavirus Disease 2019 (COVID-19) is a contagious disease that affects the respiratory system. In addition to the severe effects of the disease on health, the pandemic caused a negative impact on basic needs and services, employment, education, and economy worldwide. In Jordan, the whole country locked down, and quarantine was enforced by the military forces, which successfully controlled the spread of the disease. This research aims to study the influence of the COVID-19 pandemic and its associated quarantine on university students' beliefs about online learning practice in Jordan. An online descriptive survey involved questions that covered students' demographic information, student's basic and advanced knowledge about COVID-19, students' online learning experience during the quarantine, and finally students' views on the enforced quarantine practice in Jordan. Results showed that students have a good knowledge (>50%) about the COVID-19 basic information and a moderate knowledge (<50%) regarding COVID-19 advanced information. In general, students were pessimistic about the future of COVID-19 both locally and worldwide. Although some students acknowledged that they learned new skills in the fields of electronics, informatics, and computer software during the pandemic, most of them were unsatisfied about the quality and quantity of the given material, online exams, and the evaluation processes. Unfortunately, most of the students faced internet technical problems or challenges to electronic accessibility. The majority of the participants (>90%) supported the military-enforced quarantine implemented in the country despite the hard time the students had during the quarantine. We conclude that university students were able to protect themselves from COVID-19 through their good knowledge about the infectious disease and their commitment to follow the rules imposed by the Government of Jordan. Nevertheless, the challenges caused by the pandemic and its associated quarantine, combined with the sudden unprecedented online experience, negatively impacted students' thoughts and beliefs about the online learning experience during the quarantine. Further studies need to be performed in this context. We hope our results will help decision-makers better understand the students' attitudes and motivation toward online learning and how this will affect their future plans and decisions.

Front Public Health2020       LitCov and CORD-19
319The Rapid Development and Early Success of Covid 19 Vaccines Have Raised Hopes for Accelerating the Cancer Treatment Mechanism  

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Arch Razi Inst2021       LitCov and CORD-19
320Mental Health and the Covid-19 Pandemic  

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N Engl J Med2020       LitCov and CORD-19
321SEROEPIDEMIOLOGIC STUDIES OF CORONAVIRUS INFECTION IN ADULTS AND CHILDREN  

McIntosh, K. A. Z. Kapikian, H. C Turner, J. W. Hartley, R. H. Parrott and R. M. Chanock. (Lab. of Infectious Diseases, NIAID, NIH, Bethesda, Md. 20014) Sero-epidemiologic studies of coronavirus infection in adults and children. Amer. J. Epid., 1970, 97: 585–592-A seroepidemiologic study of infection by coronavirus strains 229E, OC38, OC43, and mouse hepatitis virus (MHV) strain A-59, is described. In adults with upper respiratory disease, two “outbreaks” of coronavirus infection occurred, one during the winter of 1965–1966 associated with complement fixing (CF) antibody responses to OC38, OC43 and MHV, and the other during the following winter associated with CF antibody responses to 229E. In hospitalized children, infection with 229E was rare; infection with OC38, OC43, and MHV occurred less often in hospitalized children with lower respiratory tract disease (3.5%) than in a control group with non-respiratory tract disease (8.2%). The limitations of the CF test using available coronavirus antigens are discussed.

Am J Epidemiol1970       CORD-19
322Parental COVID-19 Testing of Hospitalized Children: Rethinking Infection Control in a Pandemic  

J Pediatric Infect Dis Soc2020       LitCov and CORD-19
323SARS-CoV-2 and HIV coinfection: clinical experience from Rhode Island, United States  

INTRODUCTION: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) has infected >6 million people worldwide since December 2019. Global reports of HIV/SARS‐CoV‐2 coinfection are limited. To better understand the impact of the coronavirus disease 2019 (COVID‐19) pandemic on persons with HIV and improve their care, we present an outpatient and inpatient clinical experience of HIV/SARS‐CoV‐2 coinfection from Rhode Island, US. METHODS: We describe outpatient and inpatient preparedness for the COVID‐19 pandemic, and present a case series of all known patients with HIV/SARS‐CoV‐2 coinfection at The Miriam Hospital and Rhode Island Hospital, and The Miriam Hospital Infectious Diseases and Immunology Center, in Providence, Rhode Island, US. RESULTS AND DISCUSSION: The Infectious Diseases and Immunology Center rapidly prepared for outpatient and inpatient care of persons with HIV and SARS‐CoV‐2. Between 30 March and 20 May 2020, 27 patients with HIV were diagnosed with SARS‐CoV‐2. Twenty were male, six female and one transgender female; average age was 49 years; 13/27 were Hispanic and 6/27 were African American. All had HIV viral load <200 copies/mL and were on antiretroviral therapy with CD4 count range 87 to 1441 cells/µL. Twenty‐six of the 27 had common COVID‐19 symptoms for one to twenty‐eight days and most had other co‐morbidities and/or risk factors. Nine of the 27 were hospitalized for one to thirteen days; of those, three lived in a nursing home, six received remdesivir through a clinical trial or emergency use authorization and tolerated it well; eight recovered and one died. Overall, 17% of known Center people had HIV/SARS‐CoV‐2 coinfection, whereas the comparable state‐wide prevalence was 9%. CONCLUSIONS: We highlight challenges of outpatient and inpatient HIV care in the setting of the COVID‐19 pandemic and present the largest detailed case series to date from the United States on HIV/SARS‐CoV‐2 coinfection, adding to limited global reports. The aggregated clinical findings suggest that the clinical presentation and outcomes of COVID‐19 appear consistent with those without HIV. Whether SARS‐CoV‐2 infection is more frequent among persons with HIV remains to be determined. More data are needed as we develop our understanding of how HIV and antiretroviral therapy are affected by or have an impact on this pandemic.

J Int AIDS Soc2020       LitCov and CORD-19
324Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy  

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N Engl J Med2019       CORD-19
325Safety and efficacy of antiviral combination therapy in symptomatic patients of Covid-19 infection-a randomised controlled trial (SEV-COVID Trial): A structured summary of a study protocol for a randomized controlled trial  

OBJECTIVES: 1. To compare the safety and efficacy of Hydroxychloroquine with Ribavirin and standard treatment in patients with non-severe COVID-19 infection 2. To compare the safety and efficacy of standard treatment, Lopinavir-ritonavir with Ribavarin, and Hydroxychloroquine with Ribavirin in patients with severe COVID-19 infection TRIAL DESIGN: The study is an Open label, Parallel arm design, stratified randomised controlled trial. Patients will be categorised as non-severe or severe based on predefined criteria. Those who satisfy all inclusion criteria and no exclusion criteria in the respective categories, will be randomly assigned to one of the three treatment groups in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. PARTICIPANTS: The trial will be undertaken in a tertiary care center of the country where both Covid and non-Covid patients are getting treated. All patients who are confirmed positive and admitted will be screened for the eligibility criteria and will be enrolled in the study after a written informed consent. Patients will be categorised as non-severe or severe based on predefined criteria. INCLUSION CRITERIA (ALL REQUIRED): 1. Age ≥18 years at time of participation in the study 2. Laboratory (RT-PCR) confirmed infection with SARS-CoV-2 3. Symptomatic (severe or non-severe) Covid-19 disease 4. Willingness of study participant to accept randomization to any assigned treatment arm EXCLUSION CRITERIA: 1. Use of medications that are contraindicated with Lopinavir/Ritonavir, Hydroxychloroquine/Chloroquine, or Ribavirin and that cannot be replaced or stopped 2. Patient already on antiretroviral therapy with Lopinavir-Ritonavir based regimen or on Hydroxychloroquine/Chloroquine or on Ribavirin 3. Any known contraindication to test drugs such as retinopathy and QT prolongation 4. Known allergic reaction or inability to take orally of Lopinavir-ritonavir, Hydroxychloroquine/ Chloroquine, Ribavarin 5. Pregnant or breastfeeding females 6. Receipt of any experimental treatment for 2019-nCoV (off-label, compassionate use, or trial related) within 30 days prior to participation in the present study or want to participate after enrolment INTERVENTION AND COMPARATOR: Two therapeutic interventions for non-severe category and three for severe category as described below NON-SEVERE TREATMENT ARMS (NS-GROUP): Standard Treatment for non-severe cases (STNS): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Hydration, Proper Nutrition, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. SEVERE GROUP TREATMENT ARMS (S-GROUP): Standard Treatment for severe patients (STs): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Fluid Therapy, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Oxygen supplementation (As required), Invasive ventilation (As required), Antibiotic agents for other associated infections (according to 2019 ATS/IDSA guidelines for non-ICU and ICU patients), Vasopressor support, Renal-replacement therapy, Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. MAIN OUTCOMES: Primary endpoints: (1) Time to Clinical recovery (TTCR) defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, oxygen saturation, and alleviation of cough, sustained for at least 72 hours. (2) Time to SARS-CoV-2 RT-PCR negative in upper respiratory tract specimen, time to laboratory recovery of each organ involvement. Secondary Endpoints: All causes mortality, Frequency of respiratory progression (defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support), time to defervescence (in those with fever at enrolment), frequency of requirement for supplemental oxygen or non-invasive ventilation, frequency of requirement for mechanical ventilation, frequency of serious adverse events as per DAIDS table grade of severity. Outcomes are monitored for 28 days from the time of enrolment into the study OR until the patient is discharged or death whichever is longer. RANDOMIZATION: The randomization will be done using a secured central computer-based randomization using a secure website using a central, computer-based randomisation program in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. BLINDING (MASKING): This is an open labelled study i.e. Study assigned treatment will be known to the research team, the investigators and participants. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Since it is an exploratory trial as COVID-19 being a new disease, all patients who came under the purview of the inclusion criteria within the study period (5 months duration of the recruitment period of the total 6 months duration of the study i.e. from the month of June, 2020 to October 2020) and who have consented for the study will be included. TRIAL STATUS: Protocol version:1.0 Recruitment start: June 3(rd), 2020 (Ongoing) Recruitment finish (expected): October 31(st), 2020 TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI): CTRI/2020/06/025575. Registration on 03 June 2020 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.

Trials2020       LitCov and CORD-19
326The SARS, MERS and novel coronavirus epidemics, the newest and biggest global health threats: what lessons have we learned?  

OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China. METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and COVID-19. Comparisons between the viruses were made. RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally. CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.

Int J Epidemiol2020       LitCov and CORD-19
327Exploring the Potential of Artificial Intelligence and Machine Learning to Combat COVID-19 and Existing Opportunities for LMIC: A Scoping Review  

BACKGROUND: In the face of the current time-sensitive COVID-19 pandemic, the limited capacity of healthcare systems resulted in an emerging need to develop newer methods to control the spread of the pandemic. Artificial Intelligence (AI), and Machine Learning (ML) have a vast potential to exponentially optimize health care research. The use of AI-driven tools in LMIC can help in eradicating health inequalities and decrease the burden on health systems. METHODS: The literature search for this Scoping review was conducted through the PubMed database using keywords: COVID-19, Artificial Intelligence (AI), Machine Learning (ML), and Low Middle-Income Countries (LMIC). Forty-three articles were identified and screened for eligibility and 13 were included in the final review. All the items of this Scoping review are reported using guidelines for PRISMA extension for scoping reviews (PRISMA-ScR). RESULTS: Results were synthesized and reported under 4 themes. (a) The need of AI during this pandemic: AI can assist to increase the speed and accuracy of identification of cases and through data mining to deal with the health crisis efficiently, (b) Utility of AI in COVID-19 screening, contact tracing, and diagnosis: Efficacy for virus detection can a be increased by deploying the smart city data network using terminal tracking system along-with prediction of future outbreaks, (c) Use of AI in COVID-19 patient monitoring and drug development: A Deep learning system provides valuable information regarding protein structures associated with COVID-19 which could be utilized for vaccine formulation, and (d) AI beyond COVID-19 and opportunities for Low-Middle Income Countries (LMIC): There is a lack of financial, material, and human resources in LMIC, AI can minimize the workload on human labor and help in analyzing vast medical data, potentiating predictive and preventive healthcare. CONCLUSION: AI-based tools can be a game-changer for diagnosis, treatment, and management of COVID-19 patients with the potential to reshape the future of healthcare in LMIC.

J Prim Care Community Health2020       LitCov and CORD-19
328What Was the Change in Telehealth Usage and Proportion of No-show Visits for an Orthopaedic Trauma Clinic During the COVID-19 Pandemic?  

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Clin Orthop Relat Res2020       LitCov and CORD-19
329Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study  

OBJECTIVE: To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital. DESIGN: Prospective observational cohort study with rapid data gathering and near real time analysis. SETTING: 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission. PARTICIPANTS: 20 133 hospital inpatients with covid-19. MAIN OUTCOME MEASURES: Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital. RESULTS: The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital. CONCLUSIONS: ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks. STUDY REGISTRATION: ISRCTN66726260.

BMJ2020       LitCov and CORD-19
330AN ELECTRON MICROSCOPE STUDY OF THE DEVELOPMENT OF A MOUSE HEPATITIS VIRUS IN TISSUE CULTURE CELLS  

Samples taken at different intervals of time from suspension cultures of the NCTC 1469 line of mouse liver—derived (ML) cells infected with a mouse hepatitis virus have been studied with the electron microscope. The experiments revealed that the viruses are incorporated into the cells by viropexis within 1 hour after being added to the culture. An increasing number of particles are found later inside dense cytoplasmic corpuscles similar to lysosomes. In the cytoplasm of the cells from the samples taken 7 hours after inoculation, two organized structures generally associated and never seen in the controls are observed: one consists of dense material arranged in a reticular disposition (reticular inclusion); the other is formed by small tubules organized in a complex pattern (tubular body). No evidence has been found concerning their origin. Their significance is discussed. With the progression of the infection a system of membrane-bounded tubules and cisternae is differentiated in the cytoplasm of the ML cells. In the lumen of these tubules or cisternae, which are occupied by a dense material, numerous virus particles are observed. The virus particles which originate in association with the limiting membranes of tubules and cisternae are released into their lumen by a budding process. The virus particles are 75 mµ in diameter and possess a nucleoid constituted of dense particles or rods limiting an electron transparent core. The virus limiting membrane is sometimes covered by an outer layer of a dense material. In the cells from the samples taken 14 to 20 hours after inoculation, larger zones of the cell cytoplasm are occupied by inclusion bodies formed by channels or cisternae with their lumens containing numerous virus particles. In the samples taken 20 hours or more after the inoculation numerous cells show evident signs of degeneration.

J Cell Biol1965       CORD-19
331Evidence of airborne transmission of the severe acute respiratory syndrome virus  

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N Engl J Med2004       CORD-19
332COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy and Follow-Up: JACC State-of-the-Art Review  

Abstract Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.

J Am Coll Cardiol2020       LitCov and CORD-19
333The sudden transition to synchronized online learning during the COVID-19 pandemic in Saudi Arabia: a qualitative study exploring medical students' perspectives  

BACKGROUND: The closure of educational activities in the Kingdom of Saudi Arabia due to the ongoing COVID-19 pandemic resulted in an unplanned shift from traditional learning to a setup that exclusively involves digital teaching and learning. Within this context, the present study aimed to explore undergraduate medical students’ perceptions regarding the effectiveness of synchronized online learning at Unaizah College of Medicine and Medical Sciences, Qassim University, Saudi Arabia. METHODS: A qualitative study was conducted using virtual focus group discussions synchronously with the help of a discussion guide consisting of seven open-ended questions. Overall, 60 medical students were recruited using a maximum variation sampling technique; these students then participated in eight focus group discussions. All interviews were recorded, transcribed verbatim, and analyzed for thematic contents using the standard (Mayring, Kiger. M. E. and Braun.V) content analysis framework. RESULTS: A thematic content analysis yielded four core themes: (1) educational impact, (2) time management, (3) challenges encountered, and (4) preferences for the future. The online modality was well-received, and all participants agreed that online sessions were time saving and that their performance was improved due to enhanced utility of time; however, they indicated that they encountered some challenges, including methodological, content perception, technical, and behavioral challenges during sessions and online exams. Most of the preclinical students preferred online learning for the upcoming academic years. CONCLUSION: Synchronized online classes were well-accepted by the medical students. This represents significant and promising potential for the future of medical education. The principles of the online learning model and learning outcomes should be rigorously and regularly evaluated to monitor its effectiveness.

BMC Med Educ2020       LitCov and CORD-19
334A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: implications and policy recommendations  

The Coronavirus Disease 2019 (COVID-19) epidemic emerged in Wuhan, China, spread nationwide and then onto half a dozen other countries between December 2019 and early 2020. The implementation of unprecedented strict quarantine measures in China has kept a large number of people in isolation and affected many aspects of people’s lives. It has also triggered a wide variety of psychological problems, such as panic disorder, anxiety and depression. This study is the first nationwide large-scale survey of psychological distress in the general population of China during the COVID-19 epidemic.

Gen Psychiatr2020       LitCov and CORD-19
335Do psychiatric patients experience more psychiatric symptoms during COVID-19 pandemic and lockdown? A case-control study with service and research implications for immunopsychiatry  

Abstract This study aimed to assess and compare the immediate stress and psychological impact experienced by people with and without psychiatric illnesses during the peak of 2019 coronavirus disease (COVID-19) epidemic with strict lockdown measures. Seventy-six psychiatric patients and 109 healthy control subjects were recruited from Chongqing, China and completed a survey on demographic data, physical symptoms during the past 14 days and a range of psychiatric symptoms using the Impact of Event Scale- Revised (IES-R), Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI). IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. The mean IES-R, DASS-21 anxiety, depression and stress subscale and ISI scores were higher in psychiatric patients than healthy controls (p<0.001). Serious worries about their physical health, anger and impulsivity and intense suicidal ideation were significantly higher in psychiatric patients than healthy controls (p<0.05). More than one-third of psychiatric patients might fulfil the diagnostic criteria post-traumatic stress disorder (PTSD). More than one-quarter of psychiatric patients suffered from moderately severe to severe insomnia. Respondents who reported no change, poor or worse physical health status and had a psychiatric illness were significantly more likely to have higher mean IES-R, DASS depression, anxiety and stress subscale scores and ISI scores (p<0.05). This study confirms the severity of negative psychological impact on psychiatric patients during the COVID-19 epidemic with strict lockdown measures. Understanding the psychological impact on psychiatric patients during the COVID-19 pandemic has the potential to provide insight into how to develop a new immunopsychiatry service. Further research is required to compare pro-inflammatory cytokines between psychiatric patients and healthy controls during the pandemic.

Brain Behav Immun2020       LitCov and CORD-19
336Fair Allocation of Scarce Medical Resources in the Time of Covid-19  

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N Engl J Med2020       LitCov and CORD-19
337Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China  

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. METHODS: Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. RESULTS: A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. CONCLUSIONS: A period of 7–13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.

Crit Care2020       LitCov and CORD-19
338Public perceptions and experiences of social distancing and social isolation during the COVID-19 pandemic: a UK-based focus group study  

OBJECTIVE: This study explored UK public perceptions and experiences of social distancing and social isolation related to the COVID-19 pandemic. DESIGN: This qualitative study comprised five focus groups, carried out online during the early stages of the UK’s stay at home order (‘lockdown’), and analysed using a thematic approach. SETTING: Focus groups took place via online videoconferencing. PARTICIPANTS: Participants (n=27) were all UK residents aged 18 years and older, representing a range of gender, ethnic, age and occupational backgrounds. RESULTS: Qualitative analysis revealed four main themes: (1) loss—participants’ loss of (in-person) social interaction, loss of income and loss of structure and routine led to psychological and emotional ‘losses’ such as loss of motivation, loss of meaning and loss of self-worth; (2) criticisms of government communication—participants reported a lack of trust in government and a lack of clarity in the guidelines around social distancing and isolation; (3) adherence—participants reported high self-adherence to social distancing guidelines but reported seeing or hearing of non-adherence in others; (4) uncertainty around social reintegration and the future—some participants felt they would have lingering concerns over social contact while others were eager to return to high levels of social activity. Most participants, and particularly those in low-paid or precarious employment, reported feeling that the social distancing and isolation associated with COVID-19 policy has had negative impacts on their mental health and well-being during the early stages of the UK’s ‘lockdown’. CONCLUSIONS: A rapid response is necessary in terms of public health programming to mitigate the mental health impacts of COVID-19 social distancing and isolation. Social distancing and isolation ‘exit strategies’ must account for the fact that, although some individuals will voluntarily or habitually continue to socially distance, others will seek high levels of social engagement as soon as possible.

BMJ Open2020       LitCov and CORD-19
339The trinity of COVID-19: immunity, inflammation and intervention  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

Nat Rev Immunol2020       LitCov and CORD-19
340Cloning and sequencing of the matrix protein (M) gene of turkey rhinotracheitis virus reveal a gene order different from that of respiratory syncytial virus  

Abstract Several biochemical properties and the sequence of the fusion glycoprotein (F) have indicated that turkey rhinotracheitis virus (TRTV) is a pneumovirus, subfamily Pneumovirinae of the Paramyxoviridae family. As TRTV was known to generate polycistronic mRNAs, cDNA was generated from TRTV strain U K/3 BV/85-infected Vero cell mRNAs using an oligonucleotide primer corresponding to a region of the F gene. Sequencing of four cDNAs revealed that the gene adjacent to the beginning (3′ end) of the F gene was that for the matrix (M) protein, i.e., that TRTV had the partial gene order 3′-M-F-5′. This was unexpected as human respiratory syncytial (RS) virus, the type species of the genus Pneumovirus, has the partial gene order 3′-M-SH-G-F-5′, where SH and G are the small hydrophobic protein and attachment glycoprotein, respectively. Instead TRTV resembled the Morbillivirus and Paramyxovirus genera of the Paramyxoviridae (subfamily Paramyxoviridae) which have the partial gene order 3′-M-F-5′. Two further oligonucleotides, one corresponding to a sequence near the end of the M gene and the other (oligo B) to a sequence near the beginning of the F gene, with their 5′ ends spaced 300 nucleotides apart on the basis of the cDNA sequence, were used in a polymerase chain reaction (PCR) using genomic RNA as template. Only a PCR product of 0.3 kb was obtained. The same sized product was also obtained using these oligonucleotides and genomic RNA from three other TRTV strains (SA/91 /78, UK/8544/85, and SA/2381/88) which had been grown in chicken tracheal organ cultures. In addition PCR was performed using genomic RNA from TRTV-3BV and SA/2381/88 with oligo B and another oligonucleotide near the 5′ end of the gene upstream from M, spaced 1141 nucleotides apart on the basis of the sequence data. Only a 1.14-kb PCR product was obtained. Larger products would have been expected if another gene had been situated between M and F. The absence of such larger products, plus the demonstration that infected cells contained M-F dicistronic mRNAs, supported the conclusion that in the TRTV genome the M gene is adjacent to the F gene in the order 3'-M-F-5′. The 5′ termini of the M and F mRNAs were confirmed by mRNA mapping. The TRTV M gene encoded a protein of 254 amino acids, very similar to that of RS virus (256 residues; 37% amino acid identity) but very different from that of the morbilliviruses and paramyxoviruses (approximately 350 residues). Thus, on the basis of the sequences of both the M and the F genes, TRTV is more closely related to the pneumoviruses than to the paramyxoviruses and morbilliviruses.

Virology1992       CORD-19
341Surveillance Metrics of SARS-CoV-2 Transmission in Central Asia: Longitudinal Trend Analysis  

BACKGROUND: SARS-CoV-2, the virus that caused the global COVID-19 pandemic, has severely impacted Central Asia; in spring 2020, high numbers of cases and deaths were reported in this region. The second wave of the COVID-19 pandemic is currently breaching the borders of Central Asia. Public health surveillance is necessary to inform policy and guide leaders; however, existing surveillance explains past transmissions while obscuring shifts in the pandemic, increases in infection rates, and the persistence of the transmission of COVID-19. OBJECTIVE: The goal of this study is to provide enhanced surveillance metrics for SARS-CoV-2 transmission that account for weekly shifts in the pandemic, including speed, acceleration, jerk, and persistence, to better understand the risk of explosive growth in each country and which countries are managing the pandemic successfully. METHODS: Using a longitudinal trend analysis study design, we extracted 60 days of COVID-19–related data from public health registries. We used an empirical difference equation to measure the daily number of cases in the Central Asia region as a function of the prior number of cases, level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: COVID-19 transmission rates were tracked for the weeks of September 30 to October 6 and October 7-13, 2020, in Central Asia. The region averaged 11,730 new cases per day for the first week and 14,514 for the second week. Infection rates increased across the region from 4.74 per 100,000 persons to 5.66. Russia and Turkey had the highest 7-day moving averages in the region, with 9836 and 1469, respectively, for the week of October 6 and 12,501 and 1603, respectively, for the week of October 13. Russia has the fourth highest speed in the region and continues to have positive acceleration, driving the negative trend for the entire region as the largest country by population. Armenia is experiencing explosive growth of COVID-19; its infection rate of 13.73 for the week of October 6 quickly jumped to 25.19, the highest in the region, the following week. The region overall is experiencing increases in its 7-day moving average of new cases, infection, rate, and speed, with continued positive acceleration and no sign of a reversal in sight. CONCLUSIONS: The rapidly evolving COVID-19 pandemic requires novel dynamic surveillance metrics in addition to static metrics to effectively analyze the pandemic trajectory and control spread. Policy makers need to know the magnitude of transmission rates, how quickly they are accelerating, and how previous cases are impacting current caseload due to a lag effect. These metrics applied to Central Asia suggest that the region is trending negatively, primarily due to minimal restrictions in Russia.

J Med Internet Res2021       LitCov and CORD-19
342Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed COVID-19-COVID-NET, 14 States, March 1-30, 2020  

Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.

MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
343Simultaneous detection of influenza viruses A and B using real-time quantitative PCR  

N/A

J Clin Microbiol2001       CORD-19
344The Impact of COVID-19 on Italy: A Lesson for the Future  

Int J Occup Environ Med2020       LitCov and CORD-19
345Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study  

BACKGROUND: Despite concerns that patients with liver transplants might be at increased risk of adverse outcomes from COVID-19 because of coexisting comorbidities and use of immunosuppressants, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this patient group remains unclear. We aimed to assess the clinical outcomes in these patients. METHODS: In this multicentre cohort study, we collected data on patients with laboratory-confirmed SARS-CoV-2 infection, who were older than 18 years, who had previously received a liver transplant, and for whom data had been submitted by clinicians to one of two international registries (COVID-Hep and SECURE-Cirrhosis) at the end of the patient's disease course. Patients without a known hospitalisation status or mortality outcome were excluded. For comparison, data from a contemporaneous cohort of consecutive patients with SARS-CoV-2 infection who had not received a liver transplant were collected from the electronic patient records of the Oxford University Hospitals National Health Service Foundation Trust. We compared the cohorts with regard to several outcomes (including death, hospitalisation, intensive care unit [ICU] admission, requirement for intensive care, and need for invasive ventilation). A propensity score-matched analysis was done to test for an association between liver transplant and death. FINDINGS: Between March 25 and June 26, 2020, data were collected for 151 adult liver transplant recipients from 18 countries (median age 60 years [IQR 47–66], 102 [68%] men, 49 [32%] women) and 627 patients who had not undergone liver transplantation (median age 73 years [44–84], 329 [52%] men, 298 [48%] women). The groups did not differ with regard to the proportion of patients hospitalised (124 [82%] patients in the liver transplant cohort vs 474 [76%] in the comparison cohort, p=0·106), or who required intensive care (47 [31%] vs 185 [30%], p=0·837). However, ICU admission (43 [28%] vs 52 [8%], p<0·0001) and invasive ventilation (30 [20%] vs 32 [5%], p<0·0001) were more frequent in the liver transplant cohort. 28 (19%) patients in the liver transplant cohort died, compared with 167 (27%) in the comparison cohort (p=0·046). In the propensity score-matched analysis (adjusting for age, sex, creatinine concentration, obesity, hypertension, diabetes, and ethnicity), liver transplantation did not significantly increase the risk of death in patients with SARS-CoV-2 infection (absolute risk difference 1·4% [95% CI −7·7 to 10·4]). Multivariable logistic regression analysis showed that age (odds ratio 1·06 [95% CI 1·01 to 1·11] per 1 year increase), serum creatinine concentration (1·57 [1·05 to 2·36] per 1 mg/dL increase), and non-liver cancer (18·30 [1·96 to 170·75]) were associated with death among liver transplant recipients. INTERPRETATION: Liver transplantation was not independently associated with death, whereas increased age and presence of comorbidities were. Factors other than transplantation should be preferentially considered in relation to physical distancing and provision of medical care for patients with liver transplants during the COVID-19 pandemic. FUNDING: European Association for the Study of the Liver, US National Institutes of Health, UK National Institute for Health Research.

Lancet Gastroenterol Hepatol2020       LitCov and CORD-19
346The proximal origin of SARS-CoV-2  

Nat Med2020       LitCov and CORD-19
347Telemedicine During COVID-19 and Beyond: A Practical Guide and Best Practices Multidisciplinary Approach for the Orthopedic and Neurologic Pain Physical Examination  

N/A

Pain Physician2020       LitCov and CORD-19
348Practice-Level Variation in Telemedicine Use in a Pediatric Primary Care Network During the COVID-19 Pandemic: Retrospective Analysis and Survey Study  

BACKGROUND: Telehealth, the delivery of health care through telecommunication technology, has potential to address multiple health system concerns. Despite this potential, only 15% of pediatric primary care clinicians reported using telemedicine as of 2016, with the majority identifying inadequate payment for these services as the largest barrier to their adoption. The COVID-19 pandemic led to rapid changes in payment and regulations surrounding telehealth, enabling its integration into primary care pediatrics. OBJECTIVE: Due to limited use of telemedicine in primary care pediatrics prior to the COVID-19 pandemic, much is unknown about the role of telemedicine in pediatric primary care. To address this gap in knowledge, we examined the association between practice-level telemedicine use within a large pediatric primary care network and practice characteristics, telemedicine visit diagnoses, in-person visit volumes, child-level variations in telemedicine use, and clinician attitudes toward telemedicine. METHODS: We analyzed electronic health record data from 45 primary care practices and administered a clinician survey to practice clinicians. Practices were stratified into tertiles based on rates of telemedicine use (low, intermediate, high) per 1000 patients per week during a two-week period (April 19 to May 2, 2020). By practice tertile, we compared (1) practice characteristics, (2) telemedicine visit diagnoses, (3) rates of in-person visits to the office, urgent care, and the emergency department, (4) child-level variation in telemedicine use, and (5) clinician attitudes toward telemedicine across these practices. RESULTS: Across pediatric primary care practices, telemedicine visit rates ranged from 5 to 23 telemedicine visits per 1000 patients per week. Across all tertiles, the most frequent telemedicine visit diagnoses were mental health (28%-36% of visits) and dermatologic (15%-28%). Compared to low telemedicine use practices, high telemedicine use practices had fewer in-person office visits (10 vs 16 visits per 1000 patients per week, P=.005) but more total encounters overall (in-office and telemedicine: 28 vs 22 visits per 1000 patients per week, P=.006). Telemedicine use varied with child age, race and ethnicity, and recent preventive care; however, no significant interactions existed between these characteristics and practice-level telemedicine use. Finally, clinician attitudes regarding the usability and impact of telemedicine did not vary significantly across tertiles. CONCLUSIONS: Across a network of pediatric practices, we identified significant practice-level variation in telemedicine use, with increased use associated with more varied telemedicine diagnoses, fewer in-person office visits, and increased overall primary care encounter volume. Thus, in the context of the pandemic, when underutilization of primary care was prevalent, higher practice-level telemedicine use supported pediatric primary care encounter volume closer to usual rates. Child-level telemedicine use differed by child age, race and ethnicity, and recent preventive care, building upon prior concerns about differences in access to telemedicine. However, increased practice-level use of telemedicine services was not associated with reduced or increased differences in use, suggesting that further work is needed to promote equitable access to primary care telemedicine.

J Med Internet Res2020       LitCov and CORD-19
349Public perspectives on protective measures during the COVID-19 pandemic in the Netherlands, Germany and Italy: A survey study  

BACKGROUND: The extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2. Our study aimed to describe the public belief in the effectiveness of protective measures, the reported implementation of these measures, and to identify communication channels used to acquire information on COVID-19 in European countries during the early stage of the pandemic. METHODS AND FINDINGS: An online survey available in multiple languages was disseminated starting on March 19th, 2020. After five days, we computed descriptive statistics for countries with more than 500 respondents. Each day, we assessed enacted community containment measures by stage of stringency (I-IV). In total, 9,796 adults responded, of whom 8,611 resided in the Netherlands (stage III), 604 in Germany (stage III), and 581 in Italy (stage IV). To explore possible dynamics as containment strategies intensified, we also included 1,365 responses submitted during the following week. Participants indicated support for governmental measures related to avoiding social gatherings, selective closure of public places, and hand hygiene and respiratory measures (range for all measures: 95.0%-99.7%). Respondents from the Netherlands less frequently considered a complete social lockdown effective (59.2%), compared to respondents in Germany (76.6%) or Italy (87.2%). Italian residents applied enforced social distancing measures more frequently (range: 90.2%-99.3%, German and Dutch residents: 67.5%-97.0%) and self-initiated hygienic and social distancing behaviors (range: 36.3%-96.6%, German and Dutch residents: 28.3%-95.7%). Respondents reported being sufficiently informed about the outbreak and behaviors to avoid infection (range: 90.2%-91.1%). Information channels most commonly reported included television newspapers, official health websites, and social media. One week later, we observed no major differences in submitted responses. CONCLUSIONS: During the early stage of the COVID-19 pandemic, belief in the effectiveness of protective measures among survey respondents from three European countries was high and participants reported feeling sufficiently informed. In March 2020, implementation of measures differed between countries and were highest among respondents from Italy, who were subjected to the most stringent lockdown measures and greatest COVID-19 burden in Europe during this period.

PLoS One2020       LitCov and CORD-19
350Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity  

N/A

Proc Natl Acad Sci U S A2004       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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