\ 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
451Acute kidney injury associated with COVID-19: A retrospective cohort study  

BACKGROUND: Initial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19–associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom. METHODS AND FINDINGS: We extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19–negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p < 0.001), had a greater proportion of men (56.6% versus 44.9%, p < 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p < 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19–positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19–negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p < 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p < 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p < 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ≥85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region. CONCLUSIONS: We observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this. TRIAL REGISTRATION: ClinicalTrials.gov NCT04407156

PLoS Med2020       LitCov and CORD-19
452Technical guidelines for seasonal influenza vaccination in China (2021-2022)  

N/A

Zhonghua Liu Xing Bing Xue Za 2021       LitCov and CORD-19
453Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection  

Background & Aims: Severe acute respiratory syndrome (SARS) is a recently emerged infection from a novel coronavirus (CoV). Apart from fever and respiratory complications, gastrointestinal symptoms are frequently observed in patients with SARS but the significance remains undetermined. Herein, we describe the clinical, pathologic, and virologic features of the intestinal involvement of this new viral infection. Methods: A retrospective analysis of the gastrointestinal symptoms and other clinical parameters of the first 138 patients with confirmed SARS admitted for a major outbreak in Hong Kong in March 2003 was performed. Intestinal specimens were obtained by colonoscopy or postmortem examination to detect the presence of coronavirus by electron microscopy, virus culture, and reverse-transcription polymerase chain reaction. Results: Among these 138 patients with SARS, 28 (20.3%) presented with watery diarrhea and up to 38.4% of patients had symptoms of diarrhea during the course of illness. Diarrhea was more frequently observed during the first week of illness. The mean number of days with diarrhea was 3.7 ± 2.7, and most diarrhea was self-limiting. Intestinal biopsy specimens obtained by colonoscopy or autopsy showed minimal architectural disruption but the presence of active viral replication within both the small and large intestine. Coronavirus was also isolated by culture from these specimens, and SARS-CoV RNA can be detected in the stool of patients for more than 10 weeks after symptom onset. Conclusions: Diarrhea is a common presenting symptom of SARS. The intestinal tropism of the SARS-CoV has major implications on clinical presentation and viral transmission.

Gastroenterology2003       CORD-19
454Differences of SARS-CoV-2 Shedding Duration in Sputum and Nasopharyngeal Swab Specimens Among Adult Inpatients With COVID-19  

Abstract Background The viral shedding duration of SARS-CoV-2 has not been fully defined. Consecutive detection of SARS-CoV-2 RNA from respiratory tract specimens is essential for determining duration of virus shedding and providing evidence to optimize the clinical management of COVID-19. Research Question What are the shedding durations of SARS-CoV-2 RNA in upper and lower respiratory tract specimens respectively? What are their associated risk factors? Study Design and Methods: A total of 68 patients with COVID-19 admitted to Wuhan Taikang Tongji Hospital and Huoshenshan Hospital from February 10, 2020 to March 20, 2020 were recruited. Consecutive SARS-CoV-2 RNA detection from paired specimens of nasopharyngeal swab (NPS) and sputum were carried out. The clinical characteristics of patients were recorded for further analysis. Results SARS-CoV-2 RNA was detected from NPS in 48 (70.6%) patients, and from sputum specimens in 30 (44.1%) patients. The median duration of viral shedding from sputum specimens (34 days, IQR 24-40 days) was significantly longer than from NPS (19 days, IQR 14-25 days; P<0.001). Elderly age was an independent factor associated with prolonged virus shedding time of SARS-CoV-2 (HR 1.71, 1.01-2.93). It was noteworthy that in 9 patients the viral RNA was detected in sputum after NPS turned negative. Chronic lung disease and steroids were associated with virus detection in sputum, and diabetes mellitus was associated with virus detection in both NPS and sputum. Interpretation These findings may impact a test based clearance discharge criteria given patients with COVID-19 may shed virus longer in their lower respiratory tracts, with potential implication for prolonged transmission risk. In addition, more attention should be given to elderly patients who might have prolonged viral shedding duration.

Chest2020       LitCov and CORD-19
455Natural Language Processing Reveals Vulnerable Mental Health Support Groups and Heightened Health Anxiety on Reddit During COVID-19: Observational Study  

BACKGROUND: The COVID-19 pandemic is impacting mental health, but it is not clear how people with different types of mental health problems were differentially impacted as the initial wave of cases hit. OBJECTIVE: The aim of this study is to leverage natural language processing (NLP) with the goal of characterizing changes in 15 of the world’s largest mental health support groups (eg, r/schizophrenia, r/SuicideWatch, r/Depression) found on the website Reddit, along with 11 non–mental health groups (eg, r/PersonalFinance, r/conspiracy) during the initial stage of the pandemic. METHODS: We created and released the Reddit Mental Health Dataset including posts from 826,961 unique users from 2018 to 2020. Using regression, we analyzed trends from 90 text-derived features such as sentiment analysis, personal pronouns, and semantic categories. Using supervised machine learning, we classified posts into their respective support groups and interpreted important features to understand how different problems manifest in language. We applied unsupervised methods such as topic modeling and unsupervised clustering to uncover concerns throughout Reddit before and during the pandemic. RESULTS: We found that the r/HealthAnxiety forum showed spikes in posts about COVID-19 early on in January, approximately 2 months before other support groups started posting about the pandemic. There were many features that significantly increased during COVID-19 for specific groups including the categories “economic stress,” “isolation,” and “home,” while others such as “motion” significantly decreased. We found that support groups related to attention-deficit/hyperactivity disorder, eating disorders, and anxiety showed the most negative semantic change during the pandemic out of all mental health groups. Health anxiety emerged as a general theme across Reddit through independent supervised and unsupervised machine learning analyses. For instance, we provide evidence that the concerns of a diverse set of individuals are converging in this unique moment of history; we discovered that the more users posted about COVID-19, the more linguistically similar (less distant) the mental health support groups became to r/HealthAnxiety (ρ=–0.96, P<.001). Using unsupervised clustering, we found the suicidality and loneliness clusters more than doubled in the number of posts during the pandemic. Specifically, the support groups for borderline personality disorder and posttraumatic stress disorder became significantly associated with the suicidality cluster. Furthermore, clusters surrounding self-harm and entertainment emerged. CONCLUSIONS: By using a broad set of NLP techniques and analyzing a baseline of prepandemic posts, we uncovered patterns of how specific mental health problems manifest in language, identified at-risk users, and revealed the distribution of concerns across Reddit, which could help provide better resources to its millions of users. We then demonstrated that textual analysis is sensitive to uncover mental health complaints as they appear in real time, identifying vulnerable groups and alarming themes during COVID-19, and thus may have utility during the ongoing pandemic and other world-changing events such as elections and protests.

J Med Internet Res2020       LitCov and CORD-19
456Chloroquine is a potent inhibitor of SARS coronavirus infection and spread  

BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available. RESULTS: We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations. CONCLUSION: Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.

Virol J2005       CORD-19
457Clinical brief: severe acute respiratory syndrome (SARS)  

N/A

AAOHN J2003       CORD-19
458Structure of SARS coronavirus spike receptor-binding domain complexed with receptor  

N/A

Science2005       CORD-19
459SARS and MERS: recent insights into emerging coronaviruses  

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users.

Nat Rev Microbiol2016       CORD-19
460Compassionate Use of Remdesivir for Patients with Severe Covid-19  

BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)

N Engl J Med2020       LitCov and CORD-19
461Characteristics and Outcomes of 241 Births to Women With SARS-CoV-2 Infection at Five New York City Medical Centers  

N/A

Obstet Gynecol2020       LitCov and CORD-19
462A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome: A structured summary of a study p  

OBJECTIVES: Primary Objective • To evaluate the effect of ravulizumab, a long-acting complement (C5) inhibitor plus best supportive care (BSC) compared with BSC alone on the survival of patients with COVID-19. Secondary Objectives • Number of days free of mechanical ventilation at Day 29 • Duration of intensive care unit stay at Day 29 • Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 29 • Change from baseline in peripheral capillary oxygen saturation/ fraction of inspired oxygen (SpO2 /FiO2) at Day 29 • Duration of hospitalization at Day 29 • Survival (based on all-cause mortality) at Day 60 and Day 90 Safety • Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events. PK/PD/Immunogenicity • Change in serum ravulizumab concentrations over time • Change in serum free and total C5 concentrations over time • Incidence and titer of anti-ALXN1210 antibodies Biomarkers • Change in absolute level of soluble biomarkers in blood associated with complement activation, inflammatory processes, and hypercoagulable states over time Exploratory • Incidence of progression to renal failure requiring dialysis at Day 29 • Time to clinical improvement (based on a modified 6-point ordinal scale) over 29 days • SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores at Day 29 (or discharge), Day 60, and Day 90 • EuroQol 5-dimension 5-level (EQ-5D-5L) scores at Day 29 (or discharge), Day 60, and Day 90 TRIAL DESIGN: This is a multicenter Phase 3, open-label, randomized, controlled, study. The study is being conducted in acute care hospital settings in the United States, United Kingdom, Spain, France, Germany, and Japan. PARTICIPANTS: Male or female patients at least 18 years of age, weighing ≥ 40 kg, admitted to a designated hospital facility for treatment will be screened for eligibility in this study. Key Inclusion criteria • Confirmed diagnosis of SARS-CoV-2 infection (eg, via polymerase chain reaction [PCR] and/or antibody test) presenting as severe COVID-19 requiring hospitalization • Severe pneumonia, acute lung injury, or ARDS confirmed by computed tomography (CT) or X-ray at Screening or within the 3 days prior to Screening, as part of the patient’s routine clinical care • Respiratory distress requiring mechanical ventilation, which can be either invasive (requiring endotracheal intubation) or non-invasive (with continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) Key Exclusion criteria • Patient is not expected to survive for more than 24 hours • Patient is on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening • Severe pre-existing cardiac disease (ie, NYHA Class 3 or Class 4, acute coronary syndrome, or persistent ventricular tachyarrhythmias) • Patient has an unresolved Neisseria meningitidis infection Excluded medications and therapies • Current treatment with a complement inhibitor • Intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization on Day 1 Excluded prior/concurrent clinical study experience • Treatment with investigational therapy in a clinical study within 30 days before randomization, or within 5 half-lives of that investigational therapy, whichever is greater • Exceptions a. Investigational therapies will be allowed if received as part of best supportive care through an expanded access protocol or emergency approval for the treatment of COVID-19. b. Investigational antiviral therapies (such as remdesivir) will be allowed even if received as part of a clinical study. INTERVENTION AND COMPARATOR: The study consists of a Screening Period of up to 3 days, a Primary Evaluation Period of 4 weeks, a final assessment at Day 29, and a Follow-up Period of 8 weeks. For patients randomized to ravulizumab plus BSC, a weight-based dose of ravulizumab (≥40 to < 60 kg/2400 mg, 60 to < 100 kg/2700 mg, ≥ 100 kg/3000 mg) will be administered on Day 1. On Day 5 and Day 10, additional doses of 600 mg (≥40 to <60 kg) or 900 mg (>60 kg) ravulizumab will be administered and on Day 15 patients will receive 900 mg ravulizumab. There is no active or placebo comparator in this open-label clinical trial. The total duration of each patient’s participation is anticipated to be approximately 3 months. MAIN OUTCOMES: The primary efficacy outcome of this study is survival (based on all-cause mortality) at Day 29. RANDOMISATION: Patients will be randomized in a 2:1 ratio (ravulizumab plus BSC:BSC alone). Randomization will be stratified by intubated or not intubated on Day 1. Computer-generated randomization lists will be prepared by a third party under the direction of the sponsor. Investigators, or designees, will enrol patients and then obtain randomization codes using an interactive voice/web response system. The block size will be kept concealed so that investigators cannot select patients for a particular treatment assignment. Blinding (masking): This is an open-label study. Numbers to be randomised (sample size): Approximately 270 patients will be randomly assigned in a 2:1 ratio to ravulizumab plus BSC (n=180) or BSC alone (n=90). TRIAL STATUS: Protocol Number: ALXN1210-COV-305 Original Protocol: 09 Apr 2020 Protocol Amendment 1 (Global): 13 Apr 2020 Protocol Amendment 2 (Global): 17 Apr 2020 Protocol Amendment 3 (Global): 09 Jun 2020 Recruitment is currently ongoing. Recruitment was initiated on 11 May 2020. We expect recruitment to be completed by 30 Nov 2020. TRIAL REGISTRATION: Clinicaltrials.gov: Protocol Registry Number: NCT04369469; First posted; 30 Apr 2020 EU Clinical Trials Register: EudraCT Number: https://www.clinicaltrialsregister.eu/ctr-search/search?query=ALXN1210-COV-305, Start date: 07 May 2020 FULL PROTOCOL: The full redacted 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
463Prevalence, Psychological Responses and Associated Correlates of Depression, Anxiety and Stress in a Global Population, During the COVID-19 Pandemic  

Uncertainty and isolation have been linked to mental health problems. Uncertainty surrounding the COVID-19 pandemic has the potential to trigger mental health problems, which include anxiety, stress, and depression. This paper evaluates the prevalence, psychological responses, and associated correlates of depression, anxiety, and stress in a global population during the Coronavirus Disease (COVID-19) pandemic. A cross-sectional study design was adopted. 678 completed forms were collected during the COVID-19 quarantine/lockdown. An online questionnaire was designed and DASS-21 was used as the screening tool. A non-probability sampling technique strategy was applied. 50.9% of participants showed traits of anxiety, 57.4% showed signs of stress, and 58.6% exhibited depression. Stress, anxiety, and depression are overwhelmingly prevalent across the globe during this COVID-19 pandemic, and multiple factors can influence the rates of these mental health conditions. Our factorial analysis showed notable associations and manifestations of stress, anxiety, and depressive symptoms. People aged 18–24, females, and people in non-marital relationships experienced stress, anxiety, and depression. Separated individuals experienced stress and anxiety. Married people experienced anxiety. Single and divorced people experienced depression. Unemployed individuals experienced stress and depression. Students experienced anxiety and depression. Canada, the UK, and Pakistan are all countries that are experiencing stress and depression as a whole. An extended number of days in quarantine was associated with increased stress, anxiety, and depression. Family presence yielded lower levels of stress, anxiety, and depression. Lastly, lack of exercise was associated with increased stress, anxiety, and depression.

Community Ment Health J2020       LitCov and CORD-19
464Social Distancing and Transmission-reducing Practices during the COVID-19 and 2015 Middle East Respiratory Syndrome Coronavirus Outbreaks in Korea  

BACKGROUND: The absence of effective antiviral medications and vaccines increased the focus on non-pharmaceutical preventive behaviors for mitigating against the coronavirus disease 2019 (COVID-19) pandemic. To examine the current status of non-pharmaceutical preventive behaviors practiced during the COVID-19 outbreak and factors affecting behavioral activities, we compared to the 2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in Korea. METHODS: This was a serial cross-sectional population-based study in Korea with four surveys conducted on June 2 and 25, 2015 (MERS-CoV surveys), and February 4, and April 2, 2020 (COVID-19 surveys). Of 25,711 participants selected using random digit dialing numbers, 4,011 participants (aged ≥ 18 years) were successfully interviewed, for the 2020 COVID-19 (n = 2,002) and 2015 MERS-CoV (n = 2,009) epidemics were included. Participants were selected post-stratification by sex, age, and province. The total number of weighted cases in this survey equaled the total number of unweighted cases at the national level. We measured the levels of preventive behaviors (social distancing [avoiding physical contact with others]), and practicing transmission-reducing behaviors such as wearing face mask and handwashing. RESULTS: Between the surveys, respondents who reported practicing social distancing increased from 41.9%–58.2% (MERS-CoV) to 83.4%–92.3% (COVID-19). The response rate for the four surveys ranged between 13.7% and 17.7%. Practicing transmission-reducing behaviors (wearing face masks and handwashing) at least once during COVID-19 (78.8%, 80.2%) also increased compared to that during MERS-CoV (15.5%, 60.3%). The higher affective risk perception groups were more likely to practice transmission-reducing measures (adjusted odds ratio, 3.24–4.81; 95 confidence interval, 1.76–6.96) during both COVID-19 and MERS-CoV. CONCLUSION: The study findings suggest markedly increased proportions of non-pharmaceutical behavioral practices evenly across all subgroups during the two different novel virus outbreaks in Korea. Strategic interventions are needed to attempt based on preventive behavior works.

J Korean Med Sci2020       LitCov and CORD-19
465The Oxford Royal College of General Practitioners Clinical Informatics Digital Hub: Protocol to Develop Extended COVID-19 Surveillance and Trial Platforms  

BACKGROUND: Routinely recorded primary care data have been used for many years by sentinel networks for surveillance. More recently, real world data have been used for a wider range of research projects to support rapid, inexpensive clinical trials. Because the partial national lockdown in the United Kingdom due to the coronavirus disease (COVID-19) pandemic has resulted in decreasing community disease incidence, much larger numbers of general practices are needed to deliver effective COVID-19 surveillance and contribute to in-pandemic clinical trials. OBJECTIVE: The aim of this protocol is to describe the rapid design and development of the Oxford Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) and its first two platforms. The Surveillance Platform will provide extended primary care surveillance, while the Trials Platform is a streamlined clinical trials platform that will be integrated into routine primary care practice. METHODS: We will apply the FAIR (Findable, Accessible, Interoperable, and Reusable) metadata principles to a new, integrated digital health hub that will extract routinely collected general practice electronic health data for use in clinical trials and provide enhanced communicable disease surveillance. The hub will be findable through membership in Health Data Research UK and European metadata repositories. Accessibility through an online application system will provide access to study-ready data sets or developed custom data sets. Interoperability will be facilitated by fixed linkage to other key sources such as Hospital Episodes Statistics and the Office of National Statistics using pseudonymized data. All semantic descriptors (ie, ontologies) and code used for analysis will be made available to accelerate analyses. We will also make data available using common data models, starting with the US Food and Drug Administration Sentinel and Observational Medical Outcomes Partnership approaches, to facilitate international studies. The Surveillance Platform will provide access to data for health protection and promotion work as authorized through agreements between Oxford, the Royal College of General Practitioners, and Public Health England. All studies using the Trials Platform will go through appropriate ethical and other regulatory approval processes. RESULTS: The hub will be a bottom-up, professionally led network that will provide benefits for member practices, our health service, and the population served. Data will only be used for SQUIRE (surveillance, quality improvement, research, and education) purposes. We have already received positive responses from practices, and the number of practices in the network has doubled to over 1150 since February 2020. COVID-19 surveillance has resulted in tripling of the number of virology sites to 293 (target 300), which has aided the collection of the largest ever weekly total of surveillance swabs in the United Kingdom as well as over 3000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology samples. Practices are recruiting to the PRINCIPLE (Platform Randomised trial of INterventions against COVID-19 In older PeopLE) trial, and these participants will be followed up through ORCHID. These initial outputs demonstrate the feasibility of ORCHID to provide an extended national digital health hub. CONCLUSIONS: ORCHID will provide equitable and innovative use of big data through a professionally led national primary care network and the application of FAIR principles. The secure data hub will host routinely collected general practice data linked to other key health care repositories for clinical trials and support enhanced in situ surveillance without always requiring large volume data extracts. ORCHID will support rapid data extraction, analysis, and dissemination with the aim of improving future research and development in general practice to positively impact patient care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19773

JMIR Public Health Surveill2020       LitCov and CORD-19
466Timely mental Healthcare for the 2019 novel coronavirus outbreak is urgently needed  

Lancet Psychiatry2020       LitCov and CORD-19
467Diagnostic Delays for Non-melanoma Skin Cancers in Renal Transplant Recipients during the COVID-19 Pandemic: What is Hiding Behind the Mask?  

N/A

Acta Dermatovenerol Croat2021       LitCov and CORD-19
468Viruses and bacteria in the etiology of the common cold  

N/A

J Clin Microbiol1998       CORD-19
469Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. METHODS: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. RESULTS: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. CONCLUSIONS: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

N Engl J Med2020       LitCov and CORD-19
470Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths  

The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D(3) for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D(3) doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Nutrients2020       LitCov and CORD-19
471Knowledge, Concerns and Behaviors of Individuals During the First Week of the COVID-19 Pandemic in Italy  

IMPORTANCE: At the beginning of a public health crisis, such as the coronavirus disease 2019 (COVID-19) pandemic, it is important to collect information about people’s knowledge, worries, and behaviors to examine their influence on quality of life and to understand individual characteristics associated with these reactions. Such information could help to guide health authorities in providing informed interventions and clear communications. OBJECTIVES: To document the initial knowledge about COVID-19 and recommended health behaviors; to assess worries (ie, one’s perception of the influence of the worries of others on oneself), social appraisal, and preventive behaviors, comparing respondents from areas under different movement restrictions during the first week after the outbreak; and to understand how worries, perceived risk, and preventive behaviors were associated with quality of life and individual characteristics among Italian adults. DESIGN, SETTING, AND PARTICIPANTS: This convenience sample, nonprobablistic survey study recruited adult participants with a snowballing sampling method in any Italian region during the first week of the COVID-19 outbreak in Italy from February 26, 2020, to March 4, 2020. Data were analyzed from March 5 to 12, 2020. EXPOSURES: Information was collected from citizens living in the quarantine zone (ie, red zone), area with restricted movements (ie, yellow zone), and COVID-19–free regions (ie, green zone). MAIN OUTCOMES AND MEASURES: Levels of knowledge on the virus, contagion-related worries, social appraisal, and preventive behaviors were assessed with ratings of quality of life (measured using the Short Form Health Survey). Additionally, some individual characteristics that may be associated with worries and behaviors were assessed, including demographic characteristics, personality traits (measured using Big Five Inventory-10), perceived health control (measured using the internal control measure in the Health Locus of Control scale), optimism (measured using the Revised Life Orientation Test), and the need for cognitive closure (measured using the Need for Closure Scale). RESULTS: A total of 3109 individuals accessed the online questionnaire, and 2886 individuals responded to the questionnaire at least partially (mean [SD] age, 30.7 [13.2] years; 2203 [76.3%] women). Most participants were well informed about the virus characteristics and suggested behaviors, with a mean (SD) score of 77.4% (17.3%) correct answers. Quality of life was similar across the 3 zones (effect size = 0.02), but mental health was negatively associated with contagion-related worries (β = –0.066), social appraisal (β = –0.221), and preventive behaviors (β = –0.066) in the yellow zone (R(2) = 0.108). Social appraisal was also associated with reduced psychological well-being in the green zone (β = –0.205; R(2) = 0.121). In the yellow zone, higher worries were negatively correlated with emotional stability (β = –0.165; R(2) = 0.047). Emotional stability was also negatively associated with perceived susceptibility in the yellow (β = –0.108; R(2) = 0.040) and green (β = –0.170; R(2) = 0.087) zones. Preventative behaviors and social appraisal were also associated with the need for cognitive closure in both yellow (preventive behavior: β = 0.110; R(2) = 0.023; social appraisal β = 0.115; R(2) = 0.104) and green (preventive behavior: β = 0.174; R(2) = 0.022; social appraisal: 0.261; R(2) = 0.137) zones. CONCLUSIONS AND RELEVANCE: These findings suggest that during the first week of the COVID-19 outbreak in Italy, people were well informed and had a relatively stable level of worries. Quality of life did not vary across the areas, although mental well-being was challenged by the social appraisal and worries related to the contagion. Increased scores for worries and concerns were associated with more cognitive rigidity and emotional instability.

JAMA Netw Open2020       LitCov and CORD-19
472A Review of the Progress and Challenges of Developing a Vaccine for COVID-19  

A novel coronavirus, which has been designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in December 2019 in Wuhan China and causes the highly infectious disease referred to as COVID-19. COVID-19 has now spread worldwide to become a global pandemic affecting over 24 million people as of August 26th, 2020 and claimed the life of more than 800,000 people worldwide. COVID-19 is asymptomatic for some individuals and for others it can cause symptoms ranging from flu-like to acute respiratory distress syndrome (ARDS), pneumonia and death. Although it is anticipated that an effective vaccine will be available to protect against COVID-19, at present the world is relying on social distancing and hygiene measures and repurposed drugs. There is a worldwide effort to develop an effective vaccine against SARS-CoV-2 and, as of late August 2020, there are 30 vaccines in clinical trials with over 200 in various stages of development. This review will focus on the eight vaccine candidates that entered Phase 1 clinical trials in mid-May, including AstraZeneca/Oxford's AZD1222, Moderna's mRNA-1273 and Sinovac's CoronaVac vaccines, which are currently in advanced stages of vaccine development. In addition to reviewing the different stages of vaccine development, vaccine platforms and vaccine candidates, this review also discusses the biological and immunological basis required of a SARS-CoV-2 vaccine, the importance of a collaborative international effort, the ethical implications of vaccine development, the efficacy needed for an immunogenic vaccine, vaccine coverage, the potential limitations and challenges of vaccine development. Although the demand for a vaccine far surpasses the production capacity, it will be beneficial to have a limited number of vaccines available for the more vulnerable population by the end of 2020 and for the rest of the global population by the end of 2021.

Front Immunol2020       LitCov and CORD-19
473Psychosocial impact of COVID-19  

BACKGROUND: Along with its high infectivity and fatality rates, the 2019 Corona Virus Disease (COVID-19) has caused universal psychosocial impact by causing mass hysteria, economic burden and financial losses. Mass fear of COVID-19, termed as “coronaphobia”, has generated a plethora of psychiatric manifestations across the different strata of the society. So, this review has been undertaken to define psychosocial impact of COVID-19. METHODS: Pubmed and GoogleScholar are searched with the following key terms- “COVID-19”, “SARS-CoV2”, “Pandemic”, “Psychology”, “Psychosocial”, “Psychitry”, “marginalized”, “telemedicine”, “mental health”, “quarantine”, “infodemic”, “social media” and” “internet”. Few news paper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Disease itself multitude by forced quarantine to combat COVID-19 applied by nationwide lockdowns can produce acute panic, anxiety, obsessive behaviors, hoarding, paranoia, and depression, and post-traumatic stress disorder (PTSD) in the long run. These have been fueled by an “infodemic” spread via different platforms social media. Outbursts of racism, stigmatization, and xenophobia against particular communities are also being widely reported. Nevertheless, frontline healthcare workers are at higher-risk of contracting the disease as well as experiencing adverse psychological outcomes in form of burnout, anxiety, fear of transmitting infection, feeling of incompatibility, depression, increased substance-dependence, and PTSD. Community-based mitigation programs to combat COVID-19 will disrupt children's usual lifestyle and may cause florid mental distress. The psychosocial aspects of older people, their caregivers, psychiatric patients and marginalized communities are affected by this pandemic in different ways and need special attention. CONCLUSION: For better dealing with these psychosocial issues of different strata of the society, psychosocial crisis prevention and intervention models should be urgently developed by the government, health care personnel and other stakeholders. Apt application of internet services, technology and social media to curb both pandemic and infodemic needs to be instigated. Psychosocial preparedness by setting up mental organizations specific for future pandemics is certainly necessary.

Diabetes Metab Syndr2020       LitCov and CORD-19
474COVID-19 and pregnancy: what obstetricians need to know  

Coronavirus disease 2019 is an emerging disease with a rapid increase in cases and deaths since its first identification in Wuhan, China, in December 2019. Limited data are available about coronavirus disease 2019 during pregnancy; however, information on illnesses associated with other highly pathogenic coronaviruses (ie, severe acute respiratory syndrome and the Middle East respiratory syndrome) might provide insights into coronavirus disease 2019’s effects during pregnancy. Coronaviruses cause illness ranging in severity from the common cold to severe respiratory illness and death. Currently the primary epidemiologic risk factors for coronavirus disease 2019 include travel from mainland China (especially Hubei Province) or close contact with infected individuals within 14 days of symptom onset. Data suggest an incubation period of ∼5 days (range, 2–14 days). Average age of hospitalized patients has been 49–56 years, with a third to half with an underlying illness. Children have been rarely reported. Men were more frequent among hospitalized cases (54–73%). Frequent manifestations include fever, cough, myalgia, headache, and diarrhea. Abnormal testing includes abnormalities on chest radiographic imaging, lymphopenia, leukopenia, and thrombocytopenia. Initial reports suggest that acute respiratory distress syndrome develops in 17–29% of hospitalized patients. Overall case fatality rate appears to be ∼1%; however, early data may overestimate this rate. In 2 reports describing 18 pregnancies with coronavirus disease 2019, all were infected in the third trimester, and clinical findings were similar to those in nonpregnant adults. Fetal distress and preterm delivery were seen in some cases. All but 2 pregnancies were cesarean deliveries and no evidence of in utero transmission was seen. Data on severe acute respiratory syndrome and Middle East respiratory syndrome in pregnancy are sparse. For severe acute respiratory syndrome, the largest series of 12 pregnancies had a case-fatality rate of 25%. Complications included acute respiratory distress syndrome in 4, disseminated intravascular coagulopathy in 3, renal failure in 3, secondary bacterial pneumonia in 2, and sepsis in 2 patients. Mechanical ventilation was 3 times more likely among pregnant compared with nonpregnant women. Among 7 first-trimester infections, 4 ended in spontaneous abortion. Four of 5 women with severe acute respiratory syndrome after 24 weeks’ gestation delivered preterm. For Middle East respiratory syndrome, there were 13 case reports in pregnant women, of which 2 were asymptomatic, identified as part of a contact investigation; 3 patients (23%) died. Two pregnancies ended in fetal demise and 2 were born preterm. No evidence of in utero transmission was seen in severe acute respiratory syndrome or Middle East respiratory syndrome. Currently no coronavirus-specific treatments have been approved by the US Food and Drug Administration. Because coronavirus disease 2019 might increase the risk for pregnancy complications, management should optimally be in a health care facility with close maternal and fetal monitoring. Principles of management of coronavirus disease 2019 in pregnancy include early isolation, aggressive infection control procedures, oxygen therapy, avoidance of fluid overload, consideration of empiric antibiotics (secondary to bacterial infection risk), laboratory testing for the virus and coinfection, fetal and uterine contraction monitoring, early mechanical ventilation for progressive respiratory failure, individualized delivery planning, and a team-based approach with multispecialty consultations. Information on coronavirus disease 2019 is increasing rapidly. Clinicians should continue to follow the Centers for Disease Control and Prevention website to stay up to date with the latest information (https://www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html).

Am J Obstet Gynecol2020       LitCov and CORD-19
475Meaning in Life and Self-Control Buffer Stress in Times of COVID-19: Moderating and Mediating Effects With Regard to Mental Distress  

BACKGROUND: As evidenced by several studies, mental distress increased substantially during the COVID-19 pandemic. In this period, citizens were asked to exercise a high degree of self-control with regard to personal and social health behavior. At the same time, we witnessed an increase of prosocial acts and shared creative expressions, which are known to serve as sources of meaning. Meaning in life and self-control are acknowledged psychological resources. Especially in times of crisis, meaning in life has been shown to be a crucial factor for resilience and coping. However, threatening and stressful situations can also jeopardize existential security and trigger crises of meaning. The present study aimed to document levels of acute COVID-19 stress and general mental distress in Germany and Austria during the lockdown and in the weeks thereafter. In order to identify potential risk factors related to demographics and living conditions, their associations with COVID-19 stress were analyzed exploratively. The primary objective of the study, however, was to investigate the buffering effect of two psychological resources—meaningfulness and self-control—with regard to the relation between acute COVID-19 stress and general mental distress. Finally, a potential aggravation of mental distress due to the occurrence of crises of meaning was examined. METHOD: A cross-sectional survey was conducted online during lockdown (survey group 1) and the subsequent weeks characterized by eased restrictions (survey group 2). A total of N = 1,538 German-speaking participants completed a questionnaire battery including a novel measure of acute COVID-19 stress, meaningfulness and crisis of meaning (SoMe), self-control (SCS-KD), and a screening of general mental distress, measured by core symptoms of depression and anxiety (PHQ-4). In a first step, associations between living conditions, demographics, and COVID-19 stress were explored. Second, a moderation and a mediation model were tested. Meaningfulness, a measure of presence of meaning in life, as well as self-control were proposed to serve as buffers in a time of crisis, thus moderating the relation between acute COVID-19 stress and general mental distress (double moderation). Crisis of meaning, operationalizing an experienced lack of meaning in life, was proposed to mediate the relationship between acute COVID-19 stress and general mental distress, with an assumed moderation of the association between COVID-19 stress and crisis of meaning by survey group (lockdown versus eased restrictions after lockdown), and a hypothesized moderation of the link between crisis of meaning and general mental distress by self-control (dual moderated mediation). RESULTS: COVID-19 stress was slightly right-skewed. Scores were higher during lockdown than in the weeks thereafter. The rate of clinically significant general mental distress was high, exceeding prevalence rates from both the general population and clinical samples of the time before the pandemic. In the weeks following the lockdown (group 2), general mental distress and crisis of meaning were significantly higher than during lockdown (group 1), whereas meaningfulness and self-control were significantly lower. Demographically, age had the strongest association with COVID-19 stress, with older participants perceiving less acute stress (r = −.21). People who were partnered or married suffered less from COVID-19 stress (η2 = .01). Living alone (η2 = .006), living in a room versus a flat or house (η2 = .008), and being unemployed due to the pandemic (η2 = .008) were related to higher experience of COVID-19 stress. COVID-19 stress and general mental distress were strongly related (r = .53). Both meaningfulness and self-control were negatively associated with general mental distress (r = −.40 and −.36, respectively). They also moderated the relationship between COVID-19 stress and general mental distress: When meaningfulness was high, high COVID-19 stress was related to substantially lower PHQ-4 scores than when meaningfulness was low. The same held for self-control: High scores of self-control were associated with lower PHQ-4 scores especially when COVID-19 stress was high. Crisis of meaning mediated the relationship between COVID-19 stress and PHQ-4. There was a higher likelihood of crises of meaning occurring when COVID-19 stress was high; crisis of meaning, in turn, was associated with general mental distress. Survey group moderated the first path of this mediation, i.e., the relationship between COVID-19 stress and crisis of meaning: High scores of COVID-19 stress were associated more strongly with crisis of meaning in the second survey group (after the lockdown). Self-control moderated the second path, i.e., the relationship between crisis of meaning and PHQ-4: When a crisis of meaning was present, self-control could buffer its effect on general mental distress. CONCLUSIONS: Also in the present study among German-speaking participants, general mental distress was high. Scores were higher after than during the lockdown, indicating an ongoing destabilization for a significant part of the population. People who saw a meaning in their lives and who were capable of self-control reported substantially less mental distress. Meaningfulness and self-control also served as buffers between COVID-19 stress and general mental distress: When COVID-19 stress was high, the presence of meaningfulness and self-control accounted for lower general mental distress. Moreover, people who suffered strongly from COVID-19 stress were more likely to develop a crisis of meaning which, in turn, was associated with higher general mental distress. This suggests that ongoing anxiety and depression might (also) be based on existential struggles. Again here, self-control buffered the impact of crisis of meaning on general mental health. We conclude from these findings that public health policies can support citizens in coping with large-scale crises by enabling experiences of meaningfulness, e.g., through transparent and reliable modes of communicating goals and necessary intermediate steps. Moreover, health professionals are well advised to invite individuals to confront existential questions and struggles, and to encourage them to exercise self-control. The latter can be boosted by keeping higher-order goals salient—which again is inherently linked to an understanding of their meaning.

Front Psychiatry2020       LitCov and CORD-19
476Effect of COVID-19 pandemic on provision of sexual and reproductive health services in primary health facilities in Nigeria: a cross-sectional study  

BACKGROUND: Nigeria, like many other countries, has been severely affected by the COVID-19 pandemic. While efforts have been devoted to curtailing the disease, a major concern has been its potential effects on the delivery and utilization of reproductive health care services in the country. The objective of the study was to investigate the extent to which the COVID-19 pandemic and related lockdowns had affected the provision of essential reproductive, maternal, child, and adolescent health (RMCAH) services in primary health care facilities across the Nigerian States. METHODS: This was a cross-sectional study of 307 primary health centres (PHCs) in 30 Local Government Areas in 10 States, representing the six geopolitical regions of the country. A semi-structured interviewer-administered questionnaire was used to obtain data on issues relating to access and provision of RMCAH services before, during and after COVID-19 lockdowns from the head nurses/midwives in the facilities. The questionnaire was entered into Open Data Kit mounted on smartphones. Data were analysed using frequency and percentage, summary statistics, and Kruskal–Wallis test. RESULTS: Between 76 and 97% of the PHCS offered RMCAH services before the lockdown. Except in antenatal, delivery and adolescent care, there was a decline of between 2 and 6% in all the services during the lockdown and up to 10% decline after the lockdown with variation across and within States. During the lockdown. Full-service delivery was reported by 75.2% whereas 24.8% delivered partial services. There was a significant reduction in clients’ utilization of the services during the lockdown, and the difference between States before the pandemic, during, and after the lockdown. Reported difficulties during the lockdown included stock-out of drugs (25.7%), stock-out of contraceptives (25.1%), harassment by the law enforcement agents (76.9%), and transportation difficulties (55.8%). Only 2% of the PHCs reported the availability of gowns, 18% had gloves, 90.1% had hand sanitizers, and a temperature checker was available in 94.1%. Slightly above 10% identified clients with symptoms of COVID-19. CONCLUSIONS: The large proportion of PHCs who provided RMCAH services despite the lockdown demonstrates resilience. Considering the several difficulties reported, and the limited provision of primary protective equipment more effort by the government and non-governmental agencies is recommended to strengthen delivery of sexual and reproductive health in primary health centres in Nigeria during the pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12978-021-01217-5.

Reprod Health2021       LitCov and CORD-19
477Identification and management of asymptomatic carriers of COVID-19 in China  

Influenza Other Respir Viruses2020       LitCov and CORD-19
478Impact of COVID-19 and other pandemics and epidemics on people with pre-existing mental disorders: a systematic review protocol and suggestions for clinical care  

INTRODUCTION: The current COVID-19 pandemic has resulted in high rates of infection and death, as well as widespread social disruption and a reduction in access to healthcare services and support. There is growing concern over how the pandemic, as well as measures put in place to curb the pandemic, will impact people with mental disorders. We aim to study the effect of pandemics and epidemics on mental health outcomes for people with premorbid mental disorders. METHODS AND ANALYSIS: With our predefined search strategy, we will search five databases for studies reporting on mental health outcomes in people with pre-existing mental disorders during pandemic and epidemic settings. Search dates are planned as follows: 5 May 2020 and 23 July 2020. The following databases will be searched: MEDLINE/PubMed, CINAHL, PsycINFO, MedRxiv and EMBASE. Data will be screened and extracted in duplicate by two independent reviewers. Studies involving non-clinical populations or patients diagnosed with a mental disorder during a pandemic/epidemic will be excluded. We will include data collected from all pandemics and epidemics throughout history, including the present COVID-19 pandemic. If possible, study findings will be combined in meta-analyses, and subgroup analyses will be performed. We hope that this review will shed light on the impact of pandemics and epidemics on those with pre-existing mental disorders. Knowledge generated may inform future intervention studies as well as healthcare policies. Given the potential implications of the current pandemic measures (ie, disruption of healthcare services) on mental health, we will also compile a list of existing mental health resources. ETHICS AND DISSEMINATION: No ethical approval is required for this protocol and proposed systematic review as we will only use data from previously published papers that have themselves received ethics clearance and used proper informed consent procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020179611.

BMJ Open2020       LitCov and CORD-19
479Dynamic changes in anti-SARS-CoV-2 antibodies during SARS-CoV-2 infection and recovery from COVID-19  

Deciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development.

Nat Commun2020       LitCov and CORD-19
480A prospective, randomised, double blind placebo-controlled trial to evaluate the efficacy and safety of tocilizumab in patients with severe COVID-19 pneumonia (TOC-COVID): A structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: SARS-CoV2 infection leads to a concomitant pulmonary inflammation. This inflammation is supposed to be the main driver in the pathogenesis of lung failure (Acute Respiratory Distress Syndrome) in COVID-19. Objective of this study is to evaluate the efficacy and safety of a single dose treatment with Tocilizumab in patients with severe COVID-19. We hypothesize that Tocilizumab slows down the progression of SARS-CoV-2 induced pneumonia and inflammation. We expect an improvement in pulmonary function compared to placebo-treated patients. Desirable outcomes would be that tocilizumab reduces the number of days that patients are dependent on mechanical ventilation and reduces the invasiveness of breathing assistance. Furthermore, this treatment might result in fewer admissions to intensive care units. Next to these efficacy parameters, safety of a therapy with Tocilizumab in COVID-19 patients has to be monitored closely, since immunosuppression could lead to an increased rate of bacterial infections, which could negatively influence the patient’s outcome. TRIAL DESIGN: Multicentre, prospective, 2-arm randomised (ratio 1:1), double blind, placebo-controlled trial with parallel group design. PARTICIPANTS: : 1. Proof of SARS-CoV2 (Symptoms and positive polymerase chain reaction (PCR)). 2. a. Ambient air SpO(2) ≤ 92% or b. Need of ≥ 6l O2/min or c. NIV (non-invasive ventilation) or d. IMV (invasive mechanical ventilation). 3. Age ≥ 18 years. : 1. Non-invasive or invasive mechanical ventilation ≥ 48 hours. 2. Pregnancy or breast feeding. 3. Liver injury or failure (AST/ALT ≥ 5x ULN). 4. Leukocytes < 2 × 10(3)/μl. 5. Thrombocytes < 50 × 10(3)/μl. 6. Severe bacterial infection (PCT > 3ng/ml). 7. Acute or chronic diverticulitis. 8. Immunosuppressive therapy (e.g. mycophenolate, azathioprine, methotrexate, biologicals, prednisolone >10mg/d; exceptions are: prednisolone ≤ 10mg/d, sulfasalazine or hydroxychloroquine). 9. Known active or chronic tuberculosis. 10. Known active or chronic viral hepatitis. 11. Known allergic reactions to tocilizumab or its ingredients. 12. Life expectation of less than 1 year (independent of COVID-19). 13. Participation in any other interventional clinical trial within the last 30 days before the start of this trial. 14. Simultaneous participation in other interventional trials (except for participation in COVID-19 trials) which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed. 15. Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception. The data collection of the primary follow up (28 days after randomisation) takes place during the hospital stay. Subsequently, a telephone interview on the quality of life is conducted after 6 and 12 months. Participants will be recruited from inpatients at ten medical centres in Germany. INTERVENTION AND COMPARATOR: Intervention arm: Application of 8mg/kg body weight (BW) Tocilizumab i.v. once immediately after randomisation (12 mg/kg for patients with <30kg BW; total dose should not exceed 800 mg) AND conventional treatment. Control arm: Placebo (NaCl) i.v. once immediately after randomisation AND conventional treatment. MAIN OUTCOMES: Primary endpoint is the number of ventilator free days (d) (VFD) in the first 28 days after randomisation. Non-invasive ventilation (NIV), Invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO) are defined as ventilator days. VFD’s are counted as zero if the patient dies within the first 28 days. RANDOMISATION: The randomisation code will be generated by the CTU (Clinical Trials Unit, ZKS Freiburg) using the following procedure to ensure that treatment assignment is unbiased and concealed from patients and investigator staff. Randomisation will be stratified by centre and will be performed in blocks of variable length in a ratio of 1:1 within each centre. The block lengths will be documented separately and will not be disclosed to the investigators. The randomisation code will be produced by validated programs based on the Statistical Analysis System (SAS). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 100 participants will be randomised to each group (thus 200 participants in total). TRIAL STATUS: Protocol Version: V 1.2, 16.04.2020. Recruitment began 27th April 2020 and is anticipated to be completed by December 2020. TRIAL REGISTRATION: The trial was registered before trial start in trial registries (EudraCT: No. 2020-001408-41, registered 21st April 2020, and DRKS: No. DRKS00021238, registered 22nd April 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
481COVID-19 and its implications for thrombosis and anticoagulation  

Abstract Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.

Blood2020       LitCov and CORD-19
482How has COVID-19 affected mental health nurses and the delivery of mental health nursing care in the UK? Results of a mixed-methods study  

WHAT IS KNOWN ON THE SUBJECT? During the COVID‐19 pandemic, there has been research considering the impact on medical healthcare professionals and the mental health needs of the general population. However, limited focus has been placed on mental health services or mental health staff providing care in the community and in hospitals. While nurses make up the largest section of the mental health workforce in the UK, the impact that this pandemic has had on their work has been largely ignored. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE? This paper provides a unique insight into the experiences and impact that the COVID‐19 pandemic has had on mental health nurses across a range of community and inpatient settings to understand what has changed in their work and the care they can and do provide during this crisis. This includes exploring how services have changed, the move to remote working, the impact of the protective equipment crisis on nurses and the difficult working conditions facing those in inpatient settings where there is minimal guidance provided. WHAT ARE THE IMPLICATIONS FOR PRACTICE? By understanding the impact the pandemic has had on mental health nursing care, we can understand the gaps in guidance that exist, the challenges being faced and the impact the crisis has had on care for mental health service users. By doing so, we can plan for the ongoing nature of this pandemic and the aftermath that the crisis may leave for our service users and workforce alike. ABSTRACT: INTRODUCTION: While evidence has emerged concerning the impact of COVID‐19 on the general population and the challenges facing health services, much less is known regarding how the pandemic has directly affected the delivery of mental health nursing care. AIM: This paper aimed to explore how COVID‐19 has affected the ability of mental health nurses to deliver care in community and inpatient mental health services in the UK. METHOD: We investigated staff reports regarding the impact of the COVID‐19 pandemic on mental healthcare and mental health service users in the UK, using a mixed‐methods online survey. A total of 897 nurses across a range of inpatient and community settings participated. DISCUSSION: Key themes within the data explore the following: new ways of working; remote working; risks of infection/infection control challenges; and the impact on service users. Targeted guidelines are required to support mental health nurses providing care and support during a pandemic to people in severe mental distress, often in unsuitable environments. IMPLICATIONS FOR PRACTICE: Service developments need to occur alongside tailored guidance and support for staff welfare supported by clear leadership. These findings identify areas requiring attention and investment to prepare for future crises and the consequences of the pandemic.

J Psychiatr Ment Health Nurs2021       LitCov and CORD-19
483COVID-19 Digital Health Innovation Policy: A Portal to Alternative Futures in the Making  

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OMICS2020       LitCov and CORD-19
484Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak-New York City, March 11-May 2, 2020  

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MMWR Morb Mortal Wkly Rep2020       LitCov and CORD-19
485Characteristics of peripheral blood leukocyte differential counts in patients with COVID-19  

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Zhonghua Nei Ke Za Zhi2020       LitCov and CORD-19
486Adapting Neurosurgery Practice During the COVID-19 Pandemic in the Indian Subcontinent  

ABSTRACT Background The COVID-19 pandemic has changed the practice of neurosurgery. Significant resources have been dedicated to it. The pandemic in the Indian subcontinent, when compared to the rest of the world, is relatively delayed. The neurosurgical practice cannot remain unaffected by hugely disruptive measures such as a lockdown. The inevitable rise in covid infections with its gradual relaxation continues to pose a risk for health care providers. Therefore, it is imperative to evaluate whether the pandemic has had a discernible effect on the same especially in terms of practice modifications in private establishments and publicly funded hospitals, the emotional impact on the surgeon, and the influence of social media on the psyche of the surgeon. Material and Methods An online questionnaire-based survey was prepared, with questions related to the COVID specific themes of precautions taken in outpatient services and operation theaters, the influence of social media, the economic loss incurred, and the perceptible impact of telemedicine and webinars. The links to the survey were mailed to neurosurgeons in private and public practice all over the country. The responses were anonymized to ensure free and unbiased answers to the survey questions. Results A total of 176 responses were received from all over the Indian Sub-Continent. The median age of respondents was 39years (range 32-70 yrs) and the post-residency experience was 7years (range 0-34 yrs). Respondents were an equitable mix of public and private practitioners. 46% of the respondents were practicing restricted outpatient services, more in public institutions (p=0.22) which also had a higher incidence of tele-outpatient services(26% vs 17%). Wearing surgical masks, N-95 masks, and gloves were the most commonly practised precautionary measures in outpatient services(>60%). While private practitioners were continuing elective cases(40%), public institutes were more cautious with only emergencies being operated(29%). The greatest fear among all practitioners was passing the infection to the family (75%). Social media was helpful for brainstorming queries and updating practice modifications, but some surgeons admitted to receiving threats upon social media platforms(37.5%). Depression and economic losses were palpable for approximately 30% neurosurgeons. Conclusion The survey highlights the perception of the neurosurgeons towards the pandemic and the difference in public-private practice. Suspension of elective procedures, severe curtailment of the regular outpatient appointments, drastic modifications of the normal OPD/OR practices and apprehensions related to inadequacy of safety provided by PPE usage and financial losses of private establishments were some of the visible themes in our survey results. Though telemedicine has not been as widely adopted as expected, yet online education has been favourably received.

World Neurosurg2020       LitCov and CORD-19
487Hospital outbreak of Middle East respiratory syndrome coronavirus  

N/A

N Engl J Med2013       CORD-19
488Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial  

OBJECTIVES: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below. TRIAL DESIGN: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial. PARTICIPANTS: The study will be conducted in Intensive Care Units in hospitals across the United Kingdom. Patients with moderate to severe ARDS as defined by the Berlin definition, receiving invasive mechanical ventilation and with a diagnosis of COVID-19 based on clinical diagnosis or PCR test will be eligible. Patients will be excluded for the following reasons: more than 72 hours from the onset of ARDS; age < 16 years; patient known to be pregnant; major trauma in previous 5 days; presence of any active malignancy (other than non-melanoma skin cancer); WHO Class III or IV pulmonary hypertension; venous thromboembolism currently receiving anti-coagulation or within the past 3 months; patient receiving extracorporeal life support; severe chronic liver disease (Child-Pugh > 12); Do Not Attempt Resuscitation order in place; treatment withdrawal imminent within 24 hours; prisoners; declined consent; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; previously enrolled in the REALIST trial. INTERVENTION AND COMPARATOR: Intervention: Allogeneic donor CD362 enriched human umbilical cord derived mesenchymal stromal cells (REALIST ORBCEL-C) supplied as sterile, single-use cryopreserved cell suspension of a fixed dose of 400 x10(6) cells in 40ml volume, to be diluted in Plasma-Lyte 148 to a total volume of 200mls for administration. Comparator (placebo): Plasma-Lyte 148 Solution for Infusion (200mls). The cellular product (REALIST ORBCEL-C) was developed and patented by Orbsen Therapeutics. MAIN OUTCOMES: The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is Oxygenation Index (OI) at day 7. Secondary outcomes include: OI at days 4 and 14; respiratory compliance, driving pressure and PaO(2)/FiO(2) ratio (PF ratio) at days 4, 7 and 14; Sequential Organ Failure Assessment (SOFA) score at days 4, 7 and 14; extubation and reintubation; ventilation free days at day 28; duration of mechanical ventilation; length of ICU and hospital stay; 28-day and 90-day mortality. RANDOMISATION: After obtaining informed consent, patients will be randomised via a centralised automated 24-hour telephone or web-based randomisation system (CHaRT, Centre for Healthcare Randomised Trials, University of Aberdeen). Randomisation will be stratified by recruitment centre and by vasopressor use and patients will be allocated to REALIST ORBCEL-C or placebo control in a 1:1 ratio. BLINDING (MASKING): The investigator, treating physician, other members of the site research team and participants will be blinded. The cell therapy facility and clinical trials pharmacist will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A sample size of 60 patients with 30 patients randomised to the intervention and 30 to the control group. If possible, recruitment will continue beyond 60 patients to provide more accurate and definitive trial results. The total number of patients recruited will depend on the pandemic and be guided by the data monitoring and ethics committee (DMEC). TRIAL STATUS: REALIST Phase 1 completed in January 2020 prior to the COVID-19 pandemic. This was an open label dose escalation study of REALIST ORBCEL-C in patients with ARDS. The COVID-19 pandemic emerged as REALIST Phase 2 was planned to commence and the investigator team decided to repurpose the Phase 2 trial as a COVID-19 specific trial. This decision was discussed and approved by the Trial Steering Committee (TSC) and DMEC. Submissions were made to the Research Ethics Committee (REC) and MHRA to amend the protocol to a COVID-19 specific patient population and the protocol amendment was accepted by the REC on 27(th) March 2020 and MHRA on 30(th) March 2020 respectively. Other protocol changes in this amendment included an increase in the time of onset of ARDS from 48 to 72 hours, inclusion of clinical outcomes as secondary outcomes, the provision of an option for telephone consent, an indicative sample size and provision to continue recruitment beyond this indicative sample size. The current protocol in use is version 4.0 23.03.2020 (Additional file 1). Urgent Public Health status was awarded by the NIHR on 2 April 2020 and the trial opened to recruitment and recruited the first participant the same day. At the time of publication the trial was open to recruitment at 5 sites across the UK (Belfast Health and Social Care Trust, King’s College London, Guys and St Thomas’ Hospital London, Birmingham Heartlands Hospital and the Queen Elizabeth Hospital Birmingham) and 12 patients have been recruited across these sites. Additional sites are planned to open and appropriate approvals for these are being obtained. It is estimated recruitment will continue for 6 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT 03042143 (Registered 3 Feb 2017). EudraCT 2017-000585-33 (Registered 28 Nov 2017). FULL PROTOCOL: The full protocol (version 4.0 23.03.2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Trials2020       LitCov and CORD-19
489Remotely delivered information, training and support for informal caregivers of people with dementia  

N/A

Cochrane Database Syst Rev2021       LitCov and CORD-19
490Covid-19 Outbreak Progression in Italian Regions: Approaching the Peak by the End of March in Northern Italy and First Week of April in Southern Italy  

Epidemiological figures of the SARS-CoV-2 epidemic in Italy are higher than those observed in China. Our objective was to model the SARS-CoV-2 outbreak progression in Italian regions vs. Lombardy to assess the epidemic’s progression. Our setting was Italy, and especially Lombardy, which is experiencing a heavy burden of SARS-CoV-2 infections. The peak of new daily cases of the epidemic has been reached on the 29th, while was delayed in Central and Southern Italian regions compared to Northern ones. In our models, we estimated the basic reproduction number (R(0)), which represents the average number of people that can be infected by a person who has already acquired the infection, both by fitting the exponential growth rate of the infection across a 1-month period and also by using day-by-day assessments based on single observations. We used the susceptible–exposed–infected–removed (SEIR) compartment model to predict the spreading of the pandemic in Italy. The two methods provide an agreement of values, although the first method based on exponential fit should provide a better estimation, being computed on the entire time series. Taking into account the growth rate of the infection across a 1-month period, each infected person in Lombardy has involved 4 other people (3.6 based on data of April 23rd) compared to a value of [Formula: see text] , as reported in the Chinese city of Wuhan. According to our model, Piedmont, Veneto, Emilia Romagna, Tuscany and Marche will reach an R(0) value of up to 3.5. The R(0) was 3.11 for Lazio and 3.14 for the Campania region, where the latter showed the highest value among the Southern Italian regions, followed by Apulia (3.11), Sicily (2.99), Abruzzo (3.0), Calabria (2.84), Basilicata (2.66), and Molise (2.6). The R(0) value is decreased in Lombardy and the Northern regions, while it is increased in Central and Southern regions. The expected peak of the SEIR model is set at the end of March, at a national level, with Southern Italian regions reaching the peak in the first days of April. Regarding the strengths and limitations of this study, our model is based on assumptions that might not exactly correspond to the evolution of the epidemic. What we know about the SARS-CoV-2 epidemic is based on Chinese data that seems to be different than those from Italy; Lombardy is experiencing an evolution of the epidemic that seems unique inside Italy and Europe, probably due to demographic and environmental factors.

Int J Environ Res Public Healt2020       LitCov and CORD-19
491Pro- and Anti-Inflammatory Responses in Severe COVID-19 induced Acute Respiratory Distress Syndrome-An Observational Pilot Study  

OBJECTIVES: The severity of Coronavirus Disease 2019 (COVID-19) is largely determined by the immune response. First studies indicate altered lymphocyte counts and function. However, interactions of pro- and anti-inflammatory mechanisms remain elusive. In the current study we characterized the immune responses in patients suffering from severe COVID-19-induced acute respiratory distress syndrome (ARDS). METHODS: This was a single-center retrospective study in patients admitted to the intensive care unit (ICU) with confirmed COVID-19 between March 14(th) and May 28(th) 2020 (n = 39). Longitudinal data were collected within routine clinical care, including flow-cytometry of lymphocyte subsets, cytokine analysis and growth differentiation factor 15 (GDF-15). Antibody responses against the receptor binding domain (RBD) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein were analyzed. RESULTS: All patients suffered from severe ARDS, 30.8% died. Interleukin (IL)-6 was massively elevated at every time-point. The anti-inflammatory cytokine IL-10 was concomitantly upregulated with IL-6. The cellular response was characterized by lymphocytopenia with low counts of CD8+ T cells, natural killer (NK) and naïve T helper cells. CD8+ T and NK cells recovered after 8 to 14 days. The B cell system was largely unimpeded. This coincided with a slight increase in anti-SARS-CoV-2-Spike-RBD immunoglobulin (Ig) G and a decrease in anti-SARS-CoV-2-Spike-RBD IgM. GDF-15 levels were elevated throughout ICU treatment. CONCLUSIONS: Massively elevated levels of IL-6 and a delayed cytotoxic immune defense characterized severe COVID-19-induced ARDS. The B cell response and antibody production were largely unimpeded. No obvious imbalance of pro- and anti-inflammatory mechanisms was observed, with elevated GDF-15 levels suggesting increased tissue resilience.

Front Immunol2020       LitCov and CORD-19
492Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19  

N/A

J Biol Regul Homeost Agents2020       LitCov and CORD-19
493Epidemiological characteristics of severe acute respiratory syndrome in Tianjin and the assessment of effectiveness on measures of control  

N/A

Zhonghua Liu Xing Bing Xue Za 2003       CORD-19
494Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study  

OBJECTIVE: To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults. DESIGN: Self-controlled case series study using national data on covid-19 vaccination and hospital admissions. SETTING: Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom’s health service (NHS). PARTICIPANTS: 29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study. MAIN OUTCOME MEASURES: The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events. RESULTS: The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test. CONCLUSION: Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.

BMJ2021       LitCov and CORD-19
495Update of the current knowledge on genetics, evolution, immunopathogenesis and transmission for COVID-19  

In December 2019, an acute respiratory disease caused by novel species of coronavirus (SARS-CoV-2), emerged in China and has spread throughout the world. On 11(th) March 2020, the World Health Organization (WHO) officially declared coronavirus disease 19 (COVID-19) a pandemic, severe coronavirus-mediated human disease. Based on genomic and phylogenetic studies, SARS-CoV-2 might originate from bat coronaviruses and infects humans directly or through intermediate zoonotic hosts. However, the exact origin or the host intermediate remains unknown. Genetically, SARS-CoV-2 is similar to several existing coronaviruses, particularly SARS-CoV, but differs by silent and non-silent mutations. The virus uses different transmission routes and targets cells and tissues with angiotensin-converting enzyme 2 (ACE2) protein, which makes it contagious. COVID-19 shares both the main clinical features and excessive/dysregulated cell responses with the two previous Middle East respiratory syndrome coronavirus (MERS) and severe acute respiratory syndrome coronavirus (SARS) epidemics. In this review, we provide an update of the current knowledge on the COVID-19 pandemic. Gaining a deeper understanding of SARS-CoV-2 structure, transmission routes, and molecular responses, will assist in the prevention and control of COVID-19 outbreaks in the future.

Int J Biol Sci2020       LitCov and CORD-19
496Analysis of Public Perception of the Israeli Government's Early Emergency Instructions Regarding COVID-19: Online Survey Study  

BACKGROUND: On March 11, 2020, the World Health Organization (WHO) officially declared coronavirus disease (COVID-19) to be a pandemic. This posed challenges to many countries, prominent among which is communication with the public to gain their cooperation. Israel faces different challenges from other countries in its management of the COVID-19 crisis because it is in the midst of a deep constitutional crisis. OBJECTIVE: The objective of this paper was to examine the response of the Israeli public to the government’s emergency instructions regarding the pandemic in terms of correlations between overall risk perception and crisis management; overall risk perception and economic threat perception; crisis management and compliance with behavioral guidelines; and crisis management and economic threat perception. We also made comparisons between crisis management and spokesperson credibility and between crisis management and the credibility of information sources. METHODS: The sample was established using an online survey that enabled rapid and effective distribution of an online questionnaire during the COVID-19 crisis. The self-selection online survey method of nonprobability sampling was used to recruit participants (N=1056) through social network posts asking the general public (aged ≥18 years) to answer the survey. RESULTS: Participants aged ≥65 years perceived higher personal risk compared to those aged 18-30 years (mean difference 0.33, 95% CI 0.04-0.61) and those aged 46-64 years (mean difference 0.38, 95% CI 0.12-0.64). Significant correlations were found between overall risk perception and attitudes toward crisis management (r=0.19, P<.001), overall risk perception and economic threat perception (r=0.22, P<.001), attitudes toward crisis management and compliance with behavioral guidelines (r=0.15, P<.001), and attitudes toward crisis management and economic threat perception (r=–0.15, P<.001). Participants who perceived that the prime minister was the most credible spokesperson evaluated the crisis management significantly higher than all other groups. The crisis management was evaluated significantly lower by participants who stated that infectious disease specialists were the most credible spokespersons. Participants for whom the Ministry of Health website was the most credible source of information evaluated the crisis management higher than all other groups. Participants for whom scientific articles were the most credible source of information evaluated the crisis management lower than those who perceived that the WHO/Centers for Disease Control and Prevention websites or Ministry of Health/hospital websites and health care workers were the most credible. CONCLUSIONS: The higher the public trust and evaluation of crisis management, the greater the compliance of the public with guidelines. It was also found that crisis management and information cannot be approached in the same way for the overall public. Furthermore, unlike other epidemics, the COVID-19 crisis has widespread economic and social consequences; therefore, it is impossible to focus only on health risks without communicating economic and social risks as well.

J Med Internet Res2020       LitCov and CORD-19
497Prediction models for diagnosis and prognosis of covid-19: systematic review and critical appraisal  

OBJECTIVE: To review and critically appraise published and preprint reports of prediction models for diagnosing coronavirus disease 2019 (covid-19) in patients with suspected infection, for prognosis of patients with covid-19, and for detecting people in the general population at risk of being admitted to hospital for covid-19 pneumonia. DESIGN: Rapid systematic review and critical appraisal. DATA SOURCES: PubMed and Embase through Ovid, Arxiv, medRxiv, and bioRxiv up to 24 March 2020. STUDY SELECTION: Studies that developed or validated a multivariable covid-19 related prediction model. DATA EXTRACTION: At least two authors independently extracted data using the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist; risk of bias was assessed using PROBAST (prediction model risk of bias assessment tool). RESULTS: 2696 titles were screened, and 27 studies describing 31 prediction models were included. Three models were identified for predicting hospital admission from pneumonia and other events (as proxy outcomes for covid-19 pneumonia) in the general population; 18 diagnostic models for detecting covid-19 infection (13 were machine learning based on computed tomography scans); and 10 prognostic models for predicting mortality risk, progression to severe disease, or length of hospital stay. Only one study used patient data from outside of China. The most reported predictors of presence of covid-19 in patients with suspected disease included age, body temperature, and signs and symptoms. The most reported predictors of severe prognosis in patients with covid-19 included age, sex, features derived from computed tomography scans, C reactive protein, lactic dehydrogenase, and lymphocyte count. C index estimates ranged from 0.73 to 0.81 in prediction models for the general population (reported for all three models), from 0.81 to more than 0.99 in diagnostic models (reported for 13 of the 18 models), and from 0.85 to 0.98 in prognostic models (reported for six of the 10 models). All studies were rated at high risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, and high risk of model overfitting. Reporting quality varied substantially between studies. Most reports did not include a description of the study population or intended use of the models, and calibration of predictions was rarely assessed. CONCLUSION: Prediction models for covid-19 are quickly entering the academic literature to support medical decision making at a time when they are urgently needed. This review indicates that proposed models are poorly reported, at high risk of bias, and their reported performance is probably optimistic. Immediate sharing of well documented individual participant data from covid-19 studies is needed for collaborative efforts to develop more rigorous prediction models and validate existing ones. The predictors identified in included studies could be considered as candidate predictors for new models. Methodological guidance should be followed because unreliable predictions could cause more harm than benefit in guiding clinical decisions. Finally, studies should adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guideline. SYSTEMATIC REVIEW REGISTRATION: Protocol https://osf.io/ehc47/, registration https://osf.io/wy245.

BMJ2020       LitCov and CORD-19
498Impact of COVID-19 and lockdown on mental health of children and adolescents: A narrative review with recommendations  

BACKGROUND: COVID-19 pandemic and lockdown has brought about a sense of fear and anxiety around the globe. This phenomenon has led to short term as well as long term psychosocial and mental health implications for children and adolescents. The quality and magnitude of impact on minors is determined by many vulnerability factors like developmental age, educational status, pre-existing mental health condition, being economically underprivileged or being quarantined due to infection or fear of infection. AIMS: This paper is aimed at narratively reviewing various articles related to mental-health aspects of children and adolescents impacted by COVID-19 pandemic and enforcement of nationwide or regional lockdowns to prevent further spread of infection. METHODOLOGY: We conducted a review and collected articles and advisories on mental health aspects of children and adolescents during the COVID-19 pandemic. We selected articles and thematically organized them. We put up their major findings under the thematic areas of impact on young children, school and college going students, children and adolescents with mental health challenges, economically underprivileged children, impact due to quarantine and separation from parents and the advisories of international organizations. We have also provided recommendations to the above. CONCLUSION: There is a pressing need for planning longitudinal and developmental studies, and implementing evidence based elaborative plan of action to cater to the psycho social and mental health needs of the vulnerable children and adolescents during pandemic as well as post pandemic. There is a need to ameliorate children and adolescents’ access to mental health support services geared towards providing measures for developing healthy coping mechanisms during the current crisis. For this innovative child and adolescent mental health policies policies with direct and digital collaborative networks of psychiatrists, psychologists, paediatricians, and community volunteers are deemed necessary.

Psychiatry Res2020       LitCov and CORD-19
499Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa and the UK  

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 10(10) viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p(interaction)=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Lancet2021       LitCov and CORD-19
500Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State  

N/A

JAMA2020       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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