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)
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.
Exceptional score (in top 0.01%).
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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)
| Title | Venue | Year | Impact | Source | |
|---|---|---|---|---|---|
| 651 | Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong N/A | Ann Intern Med | 2003 | CORD-19 | |
| 652 | Experience with more than 500 minimally invasive hepatic procedures N/A | Ann Surg | 2008 | CORD-19 | |
| 653 | An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study BACKGROUND: The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population. In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic. METHODS: All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic. Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications. Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria. Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively. FINDINGS: Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020. Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both. The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01). INTERPRETATION: In the past month we found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS. The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease. A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic. FUNDING: None. | Lancet | 2020 | LitCov and CORD-19 | |
| 654 | SARS-CoV-2 Surveillance in the Middle East and North Africa: Longitudinal Trend Analysis BACKGROUND: The COVID-19 pandemic has disrupted the lives of millions and forced countries to devise public health policies to reduce the pace of transmission. In the Middle East and North Africa (MENA), falling oil prices, disparities in wealth and public health infrastructure, and large refugee populations have significantly increased the disease burden of COVID-19. In light of these exacerbating factors, public health surveillance is particularly necessary to help leaders understand and implement effective disease control policies to reduce SARS-CoV-2 persistence and transmission. OBJECTIVE: The goal of this study is to provide advanced surveillance metrics, in combination with traditional surveillance, for COVID-19 transmission that account for weekly shifts in the pandemic speed, acceleration, jerk, and persistence to better understand a country’s risk for explosive growth and to better inform those who are managing the pandemic. Existing surveillance coupled with our dynamic metrics of transmission will inform health policy to control the COVID-19 pandemic until an effective vaccine is developed. METHODS: Using a longitudinal trend analysis study design, we extracted 30 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in MENA as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel data model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: The regression Wald statistic was significant (χ(2)(5)=859.5, P<.001). The Sargan test was not significant, failing to reject the validity of overidentifying restrictions (χ(2)(294)=16, P=.99). Countries with the highest cumulative caseload of the novel coronavirus include Iran, Iraq, Saudi Arabia, and Israel with 530,380, 426,634, 342,202, and 303,109 cases, respectively. Many of the smaller countries in MENA have higher infection rates than those countries with the highest caseloads. Oman has 33.3 new infections per 100,000 population while Bahrain has 12.1, Libya has 14, and Lebanon has 14.6 per 100,000 people. In order of largest to smallest number of cumulative deaths since January 2020, Iran, Iraq, Egypt, and Saudi Arabia have 30,375, 10,254, 6120, and 5185, respectively. Israel, Bahrain, Lebanon, and Oman had the highest rates of COVID-19 persistence, which is the number of new infections statistically related to new infections in the prior week. Bahrain had positive speed, acceleration, and jerk, signaling the potential for explosive growth. CONCLUSIONS: Static and dynamic public health surveillance metrics provide a more complete picture of pandemic progression across countries in MENA. Static measures capture data at a given point in time such as infection rates and death rates. By including speed, acceleration, jerk, and 7-day persistence, public health officials may design policies with an eye to the future. Iran, Iraq, Saudi Arabia, and Israel all demonstrated the highest rate of infections, acceleration, jerk, and 7-day persistence, prompting public health leaders to increase prevention efforts. | J Med Internet Res | 2021 | LitCov and CORD-19 | |
| 655 | Prevalence of Depression Symptoms in US Adults Before and During the COVID-19 Pandemic IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic and the policies to contain it have been a near ubiquitous exposure in the US with unknown effects on depression symptoms. OBJECTIVE: To estimate the prevalence of and risk factors associated with depression symptoms among US adults during vs before the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This nationally representative survey study used 2 population-based surveys of US adults aged 18 or older. During COVID-19, estimates were derived from the COVID-19 and Life Stressors Impact on Mental Health and Well-being study, conducted from March 31, 2020, to April 13, 2020. Before COVID-19 estimates were derived from the National Health and Nutrition Examination Survey, conducted from 2017 to 2018. Data were analyzed from April 15 to 20, 2020. EXPOSURES: The COVID-19 pandemic and outcomes associated with the measures to mitigate it. MAIN OUTCOMES AND MEASURES: Depression symptoms, defined using the Patient Health Questionnaire-9 cutoff of 10 or higher. Categories of depression symptoms were defined as none (score, 0-4), mild (score, 5-9), moderate (score, 10-14), moderately severe (score, 15-19), and severe (score, ≥20). RESULTS: A total of 1470 participants completed the COVID-19 and Life Stressors Impact on Mental Health and Well-being survey (completion rate, 64.3%), and after removing those with missing data, the final during–COVID-19 sample included 1441 participants (619 participants [43.0%] aged 18-39 years; 723 [50.2%] men; 933 [64.7%] non-Hispanic White). The pre–COVID-19 sample included 5065 participants (1704 participants [37.8%] aged 18-39 years; 2588 [51.4%] women; 1790 [62.9%] non-Hispanic White). Depression symptom prevalence was higher in every category during COVID-19 compared with before (mild: 24.6% [95% CI, 21.8%-27.7%] vs 16.2% [95% CI, 15.1%-17.4%]; moderate: 14.8% [95% CI, 12.6%-17.4%] vs 5.7% [95% CI, 4.8%-6.9%]; moderately severe: 7.9% [95% CI, 6.3%-9.8%] vs 2.1% [95% CI, 1.6%-2.8%]; severe: 5.1% [95% CI, 3.8%-6.9%] vs 0.7% [95% CI, 0.5%-0.9%]). Higher risk of depression symptoms during COVID-19 was associated with having lower income (odds ratio, 2.37 [95% CI, 1.26-4.43]), having less than $5000 in savings (odds ratio, 1.52 [95% CI, 1.02-2.26]), and exposure to more stressors (odds ratio, 3.05 [95% CI, 1.95-4.77]). CONCLUSIONS AND RELEVANCE: These findings suggest that prevalence of depression symptoms in the US was more than 3-fold higher during COVID-19 compared with before the COVID-19 pandemic. Individuals with lower social resources, lower economic resources, and greater exposure to stressors (eg, job loss) reported a greater burden of depression symptoms. Post–COVID-19 plans should account for the probable increase in mental illness to come, particularly among at-risk populations. | JAMA Netw Open | 2020 | LitCov and CORD-19 | |
| 656 | Global Impact of COVID-19 Infection Requiring Admission to the ICU: A Systematic Review and Meta-analysis Background The COVID-19 pandemic has placed unprecedented burden on the delivery of intensive care services worldwide. Research question What is the global point estimate of mortality and risk factors for patients admitted to intensive care units (ICUs) with severe COVID-19? Methods In this systematic review and meta-analysis Medline, Embase and the Cochrane library were searched up to 1 August 2020. Pooled prevalence of participant characteristics, clinical features and outcome data were calculated using random effects models. Subgroup analyses were based on geographical distribution, study type, quality assessment, sample size, end date and patient disposition Results Forty-five studies with 16561 patients from 17 countries across four continents were included. Patients with COVID-19 admitted to ICU had a mean age of 62·6 years (95%CI 60.4-64·7). Common comorbidities included hypertension (49·5% (44·9-54·0)) and diabetes (26·6% (22·7-30·8)). Over three-quarters developed Acute Respiratory Distress Syndrome (76·1% (65·7-85·2)). Invasive mechanical ventilation was required in 67.7% (59.1-75.7), vasopressor support in 65·9% (52.4-78.4), renal replacement therapy in 16·9% (12.1-22·2) and extracorporeal membrane oxygenation in 6·4% (4·1-9.1). The duration of ICU and hospital admission was 10·8 days (9·3-18·4) and 19·1 days (16·3-21·9) respectively with in-hospital mortality of 28·1% (23·4-33·0, I2 96%). No significant subgroup effect was observed. Interpretation Critically ill patients with COVID-19 who are admitted to ICU require substantial organ support and prolonged ICU and hospital level care. The pooled estimate of global mortality for severe COVID-19 is <1/3. | Chest | 2020 | LitCov and CORD-19 | |
| 657 | The Fear of COVID-19 Scale: Development and Initial Validation BACKGROUND: The emergence of the COVID-19 and its consequences has led to fears, worries, and anxiety among individuals worldwide. The present study developed the Fear of COVID-19 Scale (FCV-19S) to complement the clinical efforts in preventing the spread and treating of COVID-19 cases. METHODS: The sample comprised 717 Iranian participants. The items of the FCV-19S were constructed based on extensive review of existing scales on fears, expert evaluations, and participant interviews. Several psychometric tests were conducted to ascertain its reliability and validity properties. RESULTS: After panel review and corrected item-total correlation testing, seven items with acceptable corrected item-total correlation (0.47 to 0.56) were retained and further confirmed by significant and strong factor loadings (0.66 to 0.74). Also, other properties evaluated using both classical test theory and Rasch model were satisfactory on the seven-item scale. More specifically, reliability values such as internal consistency (α = .82) and test–retest reliability (ICC = .72) were acceptable. Concurrent validity was supported by the Hospital Anxiety and Depression Scale (with depression, r = 0.425 and anxiety, r = 0.511) and the Perceived Vulnerability to Disease Scale (with perceived infectability, r = 0.483 and germ aversion, r = 0.459). CONCLUSION: The Fear of COVID-19 Scale, a seven-item scale, has robust psychometric properties. It is reliable and valid in assessing fear of COVID-19 among the general population and will also be useful in allaying COVID-19 fears among individuals. | Int J Ment Health Addict | 2020 | LitCov and CORD-19 | |
| 658 | Development of a standard treatment protocol for severe acute respiratory syndrome A series of 31 patients with probable SARS, diagnosed from WHO criteria, were treated according to a treatment protocol consisting of antibacterials and a combination of ribavirin and methylprednisolone. Through experience with the first 11 patients, we were able to finalise standard dose regimens, including pulsed methylprednisolone. One patient recovered on antibacterial treatment alone, 17 showed rapid and sustained responses, and 13 achieved improvement with step-up or pulsed methylprednisolone. Four patients required short periods of non-invasive ventilation. No patient required intubation or mechanical ventilation. There was no mortality or treatment morbidity in this series. | Lancet | 2003 | CORD-19 | |
| 659 | Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19–positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf. | Ann Intern Med | 2020 | LitCov and CORD-19 | |
| 660 | The implications of preliminary screening and diagnosis: Clinical characteristics of 33 mild patients with SARS-CoV-2 infection in Hunan, China BACKGROUND: In December 2019, coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other regions. OBJECTIVES: To describe the clinical manifestations and epidemiological characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Hunan Province in 2020. STUDY DESIGN: From January 19 to February 7, 2020, 33 patients with positive in nucleic acid test of pharyngeal swab were retrospectively collected and analyzed. RESULTS: There are 33 COVID-19 patients (16 male, 17 female), and the median age was 46 years. Nineteen patients (48 %) were associated with a family cluster outbreak. Seventeen patients (52 %) had traveled or lived in Hubei Province. These patients are early mild cases, most common symptoms are fever [23 (70 %)] and cough [13 (39 %)]. Most patients' white blood cell counts are normal, while they manifest as significant reduction in lymphocytes [17/28 (61 %)]. The levels of c-reactive protein and erythrocyte sedimentation rate suggest a typical viral infection. Procalcitonin did not increase and D-dimer increased slightly. Lactate dehydrogenase (LDH) levels have elevated in most patients. CT images of these patients showed bilateral multiple plaques or nodular ground-glass opacities (68.4 %). Fecal nucleic acid results were positive in eight COVID-19 patients accompanied with diarrhea. Tear nucleic acid results were negative in six COVID-19 patients. And four asymptomatic patients were infected with SARS-CoV-2. CONCLUSIONS: The clinical symptoms, laboratory results and imaging reports of patients with COVID-19 in Hunan area are significantly different from those in Wuhan area. For non-Wuhan epidemic areas, more attention should be paid to nucleic acid test results of throat swabs and stools, and it is not easily to diagnose based on clinical symptoms and CT results. Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. Attention should be paid to asymptomatic carriers, which is of great significance for the control of the global epidemic. | J Clin Virol | 2020 | LitCov and CORD-19 | |
| 661 | Children hospitalized with severe acute respiratory syndrome-related illness in Toronto N/A | Pediatrics | 2003 | CORD-19 | |
| 662 | Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis BACKGROUND: The COVID-19 pandemic has had a significant impact on public mental health. Therefore, monitoring and oversight of the population mental health during crises such as a panedmic is an immediate priority. The aim of this study is to analyze the existing research works and findings in relation to the prevalence of stress, anxiety and depression in the general population during the COVID-19 pandemic. METHOD: In this systematic review and meta-analysis, articles that have focused on stress and anxiety prevalence among the general population during the COVID-19 pandemic were searched in the Science Direct, Embase, Scopus, PubMed, Web of Science (ISI) and Google Scholar databases, without a lower time limit and until May 2020. In order to perform a meta-analysis of the collected studies, the random effects model was used, and the heterogeneity of studies was investigated using the I(2) index. Moreover. data analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. RESULTS: The prevalence of stress in 5 studies with a total sample size of 9074 is obtained as 29.6% (95% confidence limit: 24.3–35.4), the prevalence of anxiety in 17 studies with a sample size of 63,439 as 31.9% (95% confidence interval: 27.5–36.7), and the prevalence of depression in 14 studies with a sample size of 44,531 people as 33.7% (95% confidence interval: 27.5–40.6). CONCLUSION: COVID-19 not only causes physical health concerns but also results in a number of psychological disorders. The spread of the new coronavirus can impact the mental health of people in different communities. Thus, it is essential to preserve the mental health of individuals and to develop psychological interventions that can improve the mental health of vulnerable groups during the COVID-19 pandemic. | Global Health | 2020 | LitCov and CORD-19 | |
| 663 | Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. METHODS: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. FINDINGS: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 82·6% (219 of 265) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p<0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p<0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p<0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). INTERPRETATION: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. FUNDING: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research. | Lancet | 2020 | LitCov and CORD-19 | |
| 664 | Evidence for Gastrointestinal Infection of SARS-CoV-2 | Gastroenterology | 2020 | LitCov and CORD-19 | |
| 665 | Humanitarian health computing using artificial intelligence and social media: A narrative literature review N/A | Int J Med Inform | 2018 | CORD-19 | |
| 666 | Factors associated with prolonged viral RNA shedding in patients with COVID-19 BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) is becoming a public health emergency. Data are limited on the duration and host factors related to viral shedding. METHODS: In this retrospective study, risk factors associated with severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a cohort of 113 symptomatic patients from two hospitals outside Wuhan. RESULTS: The median duration of SARS-CoV-2 RNA detection was 17 days (Interquartile Range [IQR], 13–22 days) as measured from illness onset. When comparing patients with early (<15 days) and late viral RNA clearance (≥15 days after illness onset), prolonged SARS-CoV-2 RNA shedding was associated with male sex (p=0.009), old age (p=0.033), concomitated with hypertension (p=0.009), delayed admission to hospital after illness onset (p=0.001), severe illness at admission (p=0.049), invasive mechanical ventilation (p=0.006), and corticosteroid treatment (p=0.025). Patients with longer SARS-CoV-2 RNA shedding duration had slower recovery of body temperature (p<0.001) and focal absorption on radiograph images (p<0.001) than patients with early SARS-CoV-2 RNA clearance. Male sex (odds ratio [OR], 3.24 [95% CI, 1.31–8.02]), delayed hospital admission (OR, 1.30 [95% CI, 1.10–1.54]), and invasive mechanical ventilation (OR, 9.88 [95% CI, 1.11–88.02]) were independent risk factors for prolonged SARS-CoV-2 RNA shedding. CONCLUSIONS: Male sex, delayed admission to hospital after illness onset, and invasive mechanical ventilation were associated with prolonged SARS-CoV-2 RNA shedding. Hospital admission and general treatments should be started as soon as possible in symptomatic COVID-19 patients, especially male patients. | Clin Infect Dis | 2020 | LitCov and CORD-19 | |
| 667 | Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China N/A | Science | 2004 | CORD-19 | |
| 668 | The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex N/A | J Virol | 2003 | CORD-19 | |
| 669 | PTSD symptoms among health workers and public service providers during the COVID-19 outbreak In the frontline of the pandemic stand healthcare workers and public service providers, occupations which have proven to be associated with increased mental health problems during pandemic crises. This cross-sectional, survey-based study collected data from 1773 healthcare workers and public service providers throughout Norway between March 31, 2020 and April 7, 2020, which encompasses a timeframe where all non-pharmacological interventions (NPIs) were held constant. Post-traumatic stress disorder (PTSD), anxiety and depression were assessed by the Norwegian version of the PTSD checklist (PCL-5), General Anxiety Disorder –7, and Patient Health Questionnaire-9 (PHQ-9), respectively. Health anxiety and specific predictors were assessed with specific items. Multiple regression analysis was used for predictor analysis. A total of 28.9% of the sample had clinical or subclinical symptoms of PTSD, and 21.2% and 20.5% were above the established cut-offs for anxiety and depression. Those working directly in contrast to indirectly with COVID-19 patients had significantly higher PTSD symptoms. Worries about job and economy, negative metacognitions, burnout, health anxiety and emotional support were significantly associated with PTSD symptoms, after controlling for demographic variables and psychological symptoms. Health workers and public service providers are experiencing high levels of PTSD symptoms, anxiety and depression during the COVID-19 pandemic. Health workers working directly with COVID-19 patients have significantly higher levels of PTSD symptoms and depression compared to those working indirectly. Appropriate action to monitor and reduce PTSD, anxiety, and depression among these groups of individuals working in the frontline of pandemic with crucial societal roles should be taken immediately. | PLoS One | 2020 | LitCov and CORD-19 | |
| 670 | Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of COVID-19 Angiotensin‐converting enzyme‐2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID‐19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter‐regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin‐angiotensin‐aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID‐19 severity and progression, including age, sex, ethnicity, medication and several co‐morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2‐expressing organs do not equally participate in COVID‐19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID‐19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS‐CoV‐2 infection is crucially important as it has major implications for understanding COVID‐19 pathophysiology and the development of evidence‐based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers and RAAS inhibitors. Ultimately, prevention is key to combat COVID‐19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID‐19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID‐19 severity. In addition, we discuss the relevant pathological changes resulting from SARS‐CoV‐2 infection. Finally, we highlight a selection of potential treatment modalities for COVID‐19. This article is protected by copyright. All rights reserved. | J Pathol | 2020 | LitCov and CORD-19 | |
| 671 | Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season This report updates the 2020–21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021–22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4). The 2021–22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html. Recommendations for the use of COVID-19 vaccines are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html, and additional clinical guidance is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html. Updates described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021–22 season are expected to be quadrivalent. Second, the composition of 2021–22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture–based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture–based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4. This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021–22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration–licensed indications. Updates and other information are available from CDC’s influenza website (https://www.cdc.gov/flu); vaccination and health care providers should check this site periodically for additional information. | MMWR Recomm Rep | 2021 | LitCov and CORD-19 | |
| 672 | Mouse hepatitis virus A59: mRNA structure and genetic localization of the sequence divergence from hepatotropic strain MHV-3 N/A | J Virol | 1981 | CORD-19 | |
| 673 | COVID-19 Pneumonia Diagnosis Using a Simple 2D Deep Learning Framework With a Single Chest CT Image: Model Development and Validation BACKGROUND: Coronavirus disease (COVID-19) has spread explosively worldwide since the beginning of 2020. According to a multinational consensus statement from the Fleischner Society, computed tomography (CT) is a relevant screening tool due to its higher sensitivity for detecting early pneumonic changes. However, physicians are extremely occupied fighting COVID-19 in this era of worldwide crisis. Thus, it is crucial to accelerate the development of an artificial intelligence (AI) diagnostic tool to support physicians. OBJECTIVE: We aimed to rapidly develop an AI technique to diagnose COVID-19 pneumonia in CT images and differentiate it from non–COVID-19 pneumonia and nonpneumonia diseases. METHODS: A simple 2D deep learning framework, named the fast-track COVID-19 classification network (FCONet), was developed to diagnose COVID-19 pneumonia based on a single chest CT image. FCONet was developed by transfer learning using one of four state-of-the-art pretrained deep learning models (VGG16, ResNet-50, Inception-v3, or Xception) as a backbone. For training and testing of FCONet, we collected 3993 chest CT images of patients with COVID-19 pneumonia, other pneumonia, and nonpneumonia diseases from Wonkwang University Hospital, Chonnam National University Hospital, and the Italian Society of Medical and Interventional Radiology public database. These CT images were split into a training set and a testing set at a ratio of 8:2. For the testing data set, the diagnostic performance of the four pretrained FCONet models to diagnose COVID-19 pneumonia was compared. In addition, we tested the FCONet models on an external testing data set extracted from embedded low-quality chest CT images of COVID-19 pneumonia in recently published papers. RESULTS: Among the four pretrained models of FCONet, ResNet-50 showed excellent diagnostic performance (sensitivity 99.58%, specificity 100.00%, and accuracy 99.87%) and outperformed the other three pretrained models in the testing data set. In the additional external testing data set using low-quality CT images, the detection accuracy of the ResNet-50 model was the highest (96.97%), followed by Xception, Inception-v3, and VGG16 (90.71%, 89.38%, and 87.12%, respectively). CONCLUSIONS: FCONet, a simple 2D deep learning framework based on a single chest CT image, provides excellent diagnostic performance in detecting COVID-19 pneumonia. Based on our testing data set, the FCONet model based on ResNet-50 appears to be the best model, as it outperformed other FCONet models based on VGG16, Xception, and Inception-v3. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 674 | Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history(1). An ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV)(2) suggests that this group of viruses remains a major threat and that their distribution is wider than previously recognized. Although bats have been suggested as the natural reservoirs of both viruses(3–5), attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa(5–8), but none are considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins (S) to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2)(9,10). Here, we report whole genome sequences of two novel bat CoVs from Chinese horseshoe bats (Family: Rhinolophidae) in Yunnan, China; RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat CoVs, particularly in the receptor binding domain (RDB) of the S protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat fecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses the ACE2s from human, civet and Chinese horseshoe bat for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness. | Nature | 2013 | CORD-19 | |
| 675 | COVID-19: science must not be the boy who cried wolf | J Epidemiol Community Health | 2020 | LitCov and CORD-19 | |
| 676 | Excessive Media Consumption About COVID-19 is Associated With Increased State Anxiety: Outcomes of a Large Online Survey in Russia BACKGROUND: The COVID-19 pandemic has potentially had a negative impact on the mental health and well-being of individuals and families. Anxiety levels and risk factors within particular populations are poorly described. OBJECTIVE: This study aims to evaluate confidence, understanding, trust, concerns, and levels of anxiety during the COVID-19 pandemic in the general population and assess risk factors for increased anxiety. METHODS: We launched a cross-sectional online survey of a large Russian population between April 6 and 15, 2020, using multiple social media platforms. A set of questions targeted confidence, understanding, trust, and concerns in respondents. The State-Trait Anxiety Inventory was used to measure anxiety. Multiple linear regressions were used to model predictors of COVID-19–related anxiety. RESULTS: The survey was completed by 23,756 out of 53,966 (44.0% response rate) unique visitors; of which, 21,364 were residing in 62 areas of Russia. State Anxiety Scale (S-Anxiety) scores were higher than Trait Anxiety Scale scores across all regions of Russia (median S-Anxiety score 52, IQR 44-60), exceeding published norms. Time spent following news on COVID-19 was strongly associated with an increased S-Anxiety adjusted for baseline anxiety level. One to two hours spent reading COVID-19 news was associated with a 5.46 (95% CI 5.03-5.90) point difference, 2-3 hours with a 7.06 (95% CI 6.37-7.74) point difference, and more than three hours with an 8.65 (95% CI 7.82-9.47) point difference, all compared to less than 30 minutes per day. Job loss during the pandemic was another important factor associated with higher S-Anxiety scores (3.95, 95% CI 3.31-4.58). Despite survey respondents reporting high confidence in information regarding COVID-19 as well as an understanding of health care guidance, they reported low overall trust in state and local authorities, and perception of country readiness. CONCLUSIONS: Among Russian respondents from multiple social media platforms, there was evidence of higher levels of state anxiety associated with recent job loss and increased news consumption, as well as lower than expected trust in government agencies. These findings can help inform the development of key public health messages to help reduce anxiety and raise perceived trust in governmental response to this current national emergency. Using a similar methodology, comparative surveys are ongoing in other national populations. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 677 | The SARS-CoV-2 Ivermectin Navarra-ISGlobal Trial (SAINT) to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission in low risk, nonsevere COVID-19 patients in the first 48 hours after symptoms onset: A structured summary of a study protocol for a randomized control pilot trial OBJECTIVES: The primary objective is to determine the efficacy of a single dose of ivermectin, administered to low risk, non-severe COVID-19 patients in the first 48 hours after symptom onset to reduce the proportion of patients with detectable SARS-CoV-2 RNA by Polymerase Chain Reaction (PCR) test from nasopharyngeal swab at day 7 post-treatment. 1. To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab at day 7 post treatment. 2. To assess the efficacy of ivermectin to improve symptom progression in treated patients. 3. To assess the proportion of seroconversions in treated patients at day 21. 4. To assess the safety of ivermectin at the proposed dose. 5. To determine the magnitude of immune response against SARS-CoV-2. 6. To assess the early kinetics of immunity against SARS-CoV-2. TRIAL DESIGN: SAINT is a single centre, double-blind, randomized, placebo-controlled, superiority trial with two parallel arms. Participants will be randomized to receive a single dose of 400 μg/kg ivermectin or placebo, and the number of patients in the treatment and placebo groups will be the same (1:1 ratio). PARTICIPANTS: The population for the study will be patients with a positive nasopharyngeal swab PCR test for SARS-CoV-2, with non-severe COVID-19 disease, and no risk factors for progression to severity. Vulnerable populations such as pregnant women, minors (i.e.; under 18 years old), and seniors (i.e.; over 60 years old) will be excluded. Inclusion criteria: 1. Patients diagnosed with COVID-19 in the emergency room of the Clínica Universidad de Navarra (CUN) with a positive SARS-CoV-2 PCR. 2. Residents of the Pamplona basin (“Cuenca de Pamplona”). 3. The patient must be between the ages of 18 and 60 years of age. 4. Negative pregnancy test for women of child bearing age*. 5. The patient or his/her representative, has given informed consent to participate in the study. 6. The patient should, in the PI's opinion, be able to comply with all the requirements of the clinical trial (including home follow up during isolation). Exclusion criteria: 1. Known history of ivermectin allergy. 2. Hypersensitivity to any component of ivermectin. 3. Diagnosed by the attending physician. Identified in a chest X-ray. 4. Fever or cough present for more than 48 hours. 5. Positive IgG against SARS-CoV-2 by rapid diagnostic test. 6. Age under 18 or over 60 years. 7. Immunosuppression. Chronic Obstructive Pulmonary Disease. Diabetes. Hypertension. Obesity. Acute or chronic renal failure. History of coronary disease. History of cerebrovascular disease. Current neoplasm. 8. Recent travel history to countries that are endemic for Loa loa (Angola, Cameroon, Central African Republic, Chad, Democratic Republic of Congo, Ethiopia, Equatorial, Guinea, Gabon, Republic of Congo, Nigeria and Sudan). 9. Current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir or cobicistat. Use of critical CYP3A4 substrate drugs such as warfarin. *Women of child bearing age may participate if they use a safe contraceptive method for the entire period of the study and at least one month afterwards. A woman is considered to not have childbearing capacity if she is post-menopausal (minimum of 2 years without menstruation) or has undergone surgical sterilization (at least one month before the study). The trial is currently planned at a single center, Clínica Universidad de Navarra, in Navarra (Spain), and the immunology samples will be analyzed at the Barcelona Institute for Global Health (ISGlobal), in Barcelona (Spain). Participants will be recruited by the investigators at the emergency room and/or COVID-19 area of the CUN. They will remain in the trial for a period of 28 days at their homes since they will be patients with mild disease. In the interest of public health and to contain transmission of infection, follow-up visits will be conducted in the participant's home by a clinical trial team comprising nursing and medical members. Home visits will assess clinical and laboratory parameters of the patients. INTERVENTION AND COMPARATOR: Ivermectin will be administered to the treatment group at a 400μg/Kg dose (included in the EU approved label of Stromectol and Scabioral). The control group will receive placebo. There is no current data on the efficacy of ivermectin against the virus in vivo, therefore the use of placebo in the control group is ethically justified. MAIN OUTCOMES: Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. : 1. Mean viral load as determined by PCR cycle threshold (Ct) at baseline and on days 4, 7, 14, and 21. 2. Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial. 3. Proportion of patients with seroconversion at day 21. 4. Proportion of drug-related adverse events during the trial. 5. Median levels of IgG, IgM, IgA measured by Luminex, frequencies of innate and SARS-CoV-2-specific T cells assessed by flow cytometry, median levels of inflammatory and activation markers measured by Luminex and transcriptomics. 6. Median kinetics of IgG, IgM, IgA levels during the trial, until day 28. RANDOMISATION: Eligible patients will be allocated in a 1:1 ratio using a randomization list generated by the trial statistician using blocks of four to ensure balance between the groups. A study identification code with the format “SAINT-##” (##: from 01 to 24) will be generated using a sequence of random numbers so that the randomization number does not match the subject identifier. The sequence and code used will be kept in an encrypted file accessible only to the trial statistician. A physical copy will be kept in a locked cabinet at the CUN, accessible only to the person administering the drug who will not enrol or attend to patient care. A separate set of 24 envelopes for emergency unblinding will be kept in the study file. BLINDING (MASKING): The clinical trial team and the patients will be blinded. The placebo will not be visibly identical, but it will be administered by staff not involved in the clinical care or participant follow up. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is 24 patients: 12 participants will be randomised to the treatment group and 12 participants to the control group. TRIAL STATUS: Current protocol version: 1.0 dated 16 of April 2020. Recruitment is envisioned to begin by May 14th and end by June 14th. TRIAL REGISTRATION: EudraCT number: 2020-001474-29, registered April 1(st). Clinicaltrials.gov: submitted, pending number 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. | Trials | 2020 | LitCov and CORD-19 | |
| 678 | The pathogenesis and treatment of the `Cytokine Storm' in COVID-19 Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment. | J Infect | 2020 | LitCov and CORD-19 | |
| 679 | Neurological manifestations of SARS-CoV-2 infection | Semergen | 2020 | LitCov and CORD-19 | |
| 680 | Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We monitored shedding of viral RNA and infectious virus and characterized the immune response kinetics of the first five patients quarantined in Geneva, Switzerland. High viral loads and infectious virus shedding were observed from the respiratory tract despite mild symptoms, with isolation of infectious virus and prolonged positivity by reverse transcriptase PCR (RT-PCR) until days 7 and 19 after symptom onset, respectively. Robust innate responses characterized by increases in activated CD14(+) CD16(+) monocytes and cytokine responses were observed as early as 2 days after symptom onset. Cellular and humoral severe acute respiratory syndrome (SARS)-CoV-2-specific adaptive responses were detectable in all patients. Infectious virus shedding was limited to the first week after symptom onset. A strong innate response, characterized by mobilization of activated monocytes during the first days of infection and SARS-CoV-2-specific antibodies, was detectable even in patients with mild disease. IMPORTANCE This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms. | mSphere | 2020 | LitCov and CORD-19 | |
| 681 | Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project) BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. METHODS AND FINDINGS: This is the first edition of a living systematic review of randomized clinical trials comparing the effects of all treatment interventions for participants in all age groups with COVID-19. We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane guidelines, and our 8-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and nonserious adverse events. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until August 7, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 33 randomized clinical trials enrolling a total of 13,312 participants. All trials were at overall high risk of bias. We identified one trial randomizing 6,425 participants to dexamethasone versus standard care. This trial showed evidence of a beneficial effect of dexamethasone on all-cause mortality (rate ratio 0.83; 95% confidence interval [CI] 0.75–0.93; p < 0.001; low certainty) and on mechanical ventilation (risk ratio [RR] 0.77; 95% CI 0.62–0.95; p = 0.021; low certainty). It was possible to perform meta-analysis of 10 comparisons. Meta-analysis showed no evidence of a difference between remdesivir versus placebo on all-cause mortality (RR 0.74; 95% CI 0.40–1.37; p = 0.34, I(2) = 58%; 2 trials; very low certainty) or nonserious adverse events (RR 0.94; 95% CI 0.80–1.11; p = 0.48, I(2) = 29%; 2 trials; low certainty). Meta-analysis showed evidence of a beneficial effect of remdesivir versus placebo on serious adverse events (RR 0.77; 95% CI 0.63–0.94; p = 0.009, I(2) = 0%; 2 trials; very low certainty) mainly driven by respiratory failure in one trial. Meta-analyses and trial sequential analyses showed that we could exclude the possibility that hydroxychloroquine versus standard care reduced the risk of all-cause mortality (RR 1.07; 95% CI 0.97–1.19; p = 0.17; I(2) = 0%; 7 trials; low certainty) and serious adverse events (RR 1.07; 95% CI 0.96–1.18; p = 0.21; I(2) = 0%; 7 trials; low certainty) by 20% or more, and meta-analysis showed evidence of a harmful effect on nonserious adverse events (RR 2.40; 95% CI 2.01–2.87; p < 0.00001; I(2) = 90%; 6 trials; very low certainty). Meta-analysis showed no evidence of a difference between lopinavir–ritonavir versus standard care on serious adverse events (RR 0.64; 95% CI 0.39–1.04; p = 0.07, I(2) = 0%; 2 trials; very low certainty) or nonserious adverse events (RR 1.14; 95% CI 0.85–1.53; p = 0.38, I(2) = 75%; 2 trials; very low certainty). Meta-analysis showed no evidence of a difference between convalescent plasma versus standard care on all-cause mortality (RR 0.60; 95% CI 0.33–1.10; p = 0.10, I(2) = 0%; 2 trials; very low certainty). Five single trials showed statistically significant results but were underpowered to confirm or reject realistic intervention effects. None of the remaining trials showed evidence of a difference on our predefined outcomes. Because of the lack of relevant data, it was not possible to perform other meta-analyses, network meta-analysis, or individual patient data meta-analyses. The main limitation of this living review is the paucity of data currently available. Furthermore, the included trials were all at risks of systematic errors and random errors. CONCLUSIONS: Our results show that dexamethasone and remdesivir might be beneficial for COVID-19 patients, but the certainty of the evidence was low to very low, so more trials are needed. We can exclude the possibility of hydroxychloroquine versus standard care reducing the risk of death and serious adverse events by 20% or more. Otherwise, no evidence-based treatment for COVID-19 currently exists. This review will continuously inform best practice in treatment and clinical research of COVID-19. | PLoS Med | 2020 | LitCov and CORD-19 | |
| 682 | Epidemiological, demographic and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study Summary Background Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities. Methods We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR. Findings 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]). Interpretation Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition. Funding None. | Lancet Infect Dis | 2013 | CORD-19 | |
| 683 | Interventions to mitigate early spread of SARS-CoV-2 in Singapore: a modelling study BACKGROUND: Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful. METHODS: We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [R(0)] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R(0) value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures. FINDINGS: For the baseline scenario, when R(0) was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000–320 000), corresponding to 7·4% (IQR 6·5–8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000–776 000) when R(0) was 2·0, corresponding to 19·3% (17·8–20·6) of the Singaporean population, and 1 207 000 cases (1 164 000–1 249 000) when R(0) was 2·5, corresponding to 32% (30·9–33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6–99·9) when R(0) was 1·5, by 93·0% (81·5–99·7) when R(0) was 2·0, and by 78·2% (59·0 −94·4) when R(0) was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R(0) of 1·5. INTERPRETATION: Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines. FUNDING: Singapore Ministry of Health, Singapore Population Health Improvement Centre. | Lancet Infect Dis | 2020 | LitCov and CORD-19 | |
| 684 | How do you feel during the COVID-19 pandemic? A survey using psychological and linguistic self-report measures and machine learning to investigate mental health, subjective experience, personality and behaviour during the COVID-19 pandemic among university students BACKGROUND: The WHO has raised concerns about the psychological consequences of the current COVID-19 pandemic, negatively affecting health across societies, cultures and age-groups. METHODS: This online survey study investigated mental health, subjective experience, and behaviour (health, learning/teaching) among university students studying in Egypt or Germany shortly after the first pandemic lockdown in May 2020. Psychological assessment included stable personality traits, self-concept and state-like psychological variables related to (a) mental health (depression, anxiety), (b) pandemic threat perception (feelings during the pandemic, perceived difficulties in describing, identifying, expressing emotions), (c) health (e.g., worries about health, bodily symptoms) and behaviour including perceived difficulties in learning. Assessment methods comprised self-report questions, standardized psychological scales, psychological questionnaires, and linguistic self-report measures. Data analysis comprised descriptive analysis of mental health, linguistic analysis of self-concept, personality and feelings, as well as correlational analysis and machine learning. N = 220 (107 women, 112 men, 1 = other) studying in Egypt or Germany provided answers to all psychological questionnaires and survey items. RESULTS: Mean state and trait anxiety scores were significantly above the cut off scores that distinguish between high versus low anxious subjects. Depressive symptoms were reported by 51.82% of the student sample, the mean score was significantly above the screening cut off score for risk of depression. Worries about health (mental and physical health) and perceived difficulties in identifying feelings, and difficulties in learning behaviour relative to before the pandemic were also significant. No negative self-concept was found in the linguistic descriptions of the participants, whereas linguistic descriptions of feelings during the pandemic revealed a negativity bias in emotion perception. Machine learning (exploratory) predicted personality from the self-report data suggesting relations between personality and subjective experience that were not captured by descriptive or correlative data analytics alone. CONCLUSION: Despite small sample sizes, this multimethod survey provides important insight into mental health of university students studying in Egypt or Germany and how they perceived the first COVID-19 pandemic lockdown in May 2020. The results should be continued with larger samples to help develop psychological interventions that support university students across countries and cultures to stay psychologically resilient during the pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40359-021-00574-x. | BMC Psychol | 2021 | LitCov and CORD-19 | |
| 685 | The polypeptide structure of transmissible gastroenteritis virus N/A | J Gen Virol | 1975 | CORD-19 | |
| 686 | RNA of mouse hepatitis virus N/A | J Virol | 1978 | CORD-19 | |
| 687 | V367F Mutation in SARS-CoV-2 Spike RBD Emerging during the Early Transmission Phase Enhances Viral Infectivity through Increased Human ACE2 Receptor Binding Affinity The current pandemic of COVID-19 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the critical determinant of viral tropism and infectivity. To investigate whether naturally occurring RBD mutations during the early transmission phase have altered the receptor binding affinity and infectivity, we first analyzed in silico the binding dynamics between SARS-CoV-2 RBD mutants and the human angiotensin-converting enzyme 2 (ACE2) receptor. Among 32,123 genomes of SARS-CoV-2 isolates (December 2019 through March 2020), 302 nonsynonymous RBD mutants were identified and clustered into 96 mutant types. The six dominant mutations were analyzed applying molecular dynamics simulations (MDS). The mutant type V367F continuously circulating worldwide displayed higher binding affinity to human ACE2 due to the enhanced structural stabilization of the RBD beta-sheet scaffold. The MDS also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The increased infectivity of V367 mutants was further validated by performing receptor-ligand binding enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance, and pseudotyped virus assays. Phylogenetic analysis of the genomes of V367F mutants showed that during the early transmission phase, most V367F mutants clustered more closely with the SARS-CoV-2 prototype strain than the dual-mutation variants (V367F+D614G), which may derivate from recombination. The analysis of critical RBD mutations provides further insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin under negative selection pressure and supports the continuing surveillance of spike mutations to aid in the development of new COVID-19 drugs and vaccines. IMPORTANCE A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether mutations in the RBD of the circulating SARS-CoV-2 isolates have altered the receptor binding affinity and made them more infectious has been the research hot spot. Given that SARS-CoV-2 is a novel coronavirus, the significance of our research is in identifying and validating the RBD mutant types emerging during the early transmission phase and increasing human angiotensin-converting enzyme 2 (ACE2) receptor binding affinity and infectivity. Our study provides insights into the evolutionary trajectory of early SARS-CoV-2 variants of zoonotic origin. The continuing surveillance of RBD mutations with increased human ACE2 affinity in human or other animals is critical to the development of new COVID-19 drugs and vaccines against these variants during the sustained COVID-19 pandemic. | J Virol | 2021 | LitCov and CORD-19 | |
| 688 | High Prevalence of Obesity in SARS-CoV-2 Requiring Invasive Mechanical Ventilation OBJECTIVE: The Covid‐19 pandemic is rapidly spreading worldwide, notably in Europe and North America, where obesity is highly prevalent. The relation between obesity and severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has not been fully documented. METHODS: In this retrospective cohort study we analyzed the relationship between clinical characteristics, including body mass index (BMI), and the requirement for invasive mechanical ventilation (IMV) in 124 consecutive patients admitted in intensive care for SARS‐CoV‐2, in a single French center. RESULTS: Obesity (BMI >30 kg/m2) and severe obesity (BMI >35 kg/m2) were present in 47.6% and 28.2% of cases, respectively. Overall, 85 patients (68.6%) required IMV. The proportion of patients who required IMV increased with BMI categories (p<0.01, Chi square test for trend), and it was greatest in patients with BMI >35 kg/m2 (85.7%). In multivariate logistic regression, the need for IMV was significantly associated with male sex (p<0.05) and BMI (p<0.05), independent of age, diabetes, and hypertension. The odds ratio for IMV in patients with BMI >35 kg/m2 vs patients with BMI <25 kg/m2 was 7.36 (1.63‐33.14; p=0.02) CONCLUSION: The present study showed a high frequency of obesity among patients admitted in intensive care for SARS‐CoV‐2. Disease severity increased with BMI. Obesity is a risk factor for SARS‐CoV‐2 severity requiring increased attention to preventive measures in susceptible individuals. | Obesity (Silver Spring) | 2020 | LitCov and CORD-19 | |
| 689 | Virology, Epidemiology, Pathogenesis and Control of COVID-19 The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements since the pandemic of severe acute respiratory syndrome (SARS) in 2002~2003 and Middle East respiratory syndrome (MERS) in 2012 have accelerated our understanding of the epidemiology and pathogenesis of SARS-CoV-2 and the development of therapeutics to treat viral infection. As no specific therapeutics and vaccines are available for disease control, the epidemic of COVID-19 is posing a great threat for global public health. To provide a comprehensive summary to public health authorities and potential readers worldwide, we detail the present understanding of COVID-19 and introduce the current state of development of measures in this review. | Viruses | 2020 | LitCov and CORD-19 | |
| 690 | Surveillance of Vaccination Coverage Among Adult Populations -United States, 2018 PROBLEM/CONDITION: Adults are at risk for illness, hospitalization, disability and, in some cases, death from vaccine-preventable diseases, particularly influenza and pneumococcal disease. CDC recommends vaccinations for adults on the basis of age, health conditions, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults remains low. REPORTING PERIOD: August 2017–June 2018 (for influenza vaccination) and January–December 2018 (for pneumococcal, herpes zoster, tetanus and diphtheria [Td]/tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis [Tdap], hepatitis A, hepatitis B, and human papillomavirus [HPV] vaccination). DESCRIPTION OF SYSTEM: The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. NHIS’s objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. Adult receipt of influenza, pneumococcal, herpes zoster, Td/Tdap, hepatitis A, hepatitis B, and at least 1 dose of HPV vaccines was assessed. Estimates were derived for a new composite adult vaccination quality measure and by selected demographic and access-to-care characteristics (e.g., age, race/ethnicity, indication for vaccination, travel history [travel to countries where hepatitis infections are endemic], health insurance status, contacts with physicians, nativity, and citizenship). Trends in adult vaccination were assessed during 2010−2018. RESULTS: Coverage for the adult age-appropriate composite measure was low in all age groups. Racial and ethnic differences in coverage persisted for all vaccinations, with lower coverage for most vaccinations among non-White compared with non-Hispanic White adults. Linear trend tests indicated coverage increased from 2010 to 2018 for most vaccines in this report. Few adults aged ≥19 years had received all age-appropriate vaccines, including influenza vaccination, regardless of whether inclusion of Tdap (13.5%) or inclusion of any tetanus toxoid–containing vaccine (20.2%) receipt was measured. Coverage among adults for influenza vaccination during the 2017−18 season (46.1%) was similar to the estimate for the 2016−17 season (45.4%), and coverage for pneumococcal (adults aged ≥65 years [69.0%]), herpes zoster (adults aged ≥50 years and aged ≥60 years [24.1% and 34.5%, respectively]), tetanus (adults aged ≥19 years [62.9%]), Tdap (adults aged ≥19 years [31.2%]), hepatitis A (adults aged ≥19 years [11.9%]), and HPV (females aged 19–26 years [52.8%]) vaccination in 2018 were similar to the estimates for 2017. Hepatitis B vaccination coverage among adults aged ≥19 years and health care personnel (HCP) aged ≥19 years increased 4.2 and 6.7 percentage points to 30.0% and 67.2%, respectively, from 2017. HPV vaccination coverage among males aged 19–26 years increased 5.2 percentage points to 26.3% from the 2017 estimate. Overall, HPV vaccination coverage among females aged 19–26 years did not increase, but coverage among Hispanic females aged 19–26 years increased 10.8 percentage points to 49.6% from the 2017 estimate. Coverage for the following vaccines was lower among adults without health insurance compared with those with health insurance: influenza vaccine (among adults aged ≥19 years, 19–49 years, and 50–64 years), pneumococcal vaccine (among adults aged 19–64 years at increased risk), Td vaccine (among all age groups), Tdap vaccine (among adults aged ≥19 years and 19–64 years), hepatitis A vaccine (among adults aged ≥19 years overall and among travelers aged ≥19 years), hepatitis B vaccine (among adults aged ≥19 years and 19–49 years and among travelers aged ≥19 years), herpes zoster vaccine (among adults aged ≥60 years), and HPV vaccine (among males and females aged 19–26 years). Adults who reported having a usual place for health care generally reported receipt of recommended vaccinations more often than those who did not have such a place, regardless of whether they had health insurance. Vaccination coverage was higher among adults reporting ≥1 physician contact during the preceding year compared with those who had not visited a physician during the preceding year, regardless of whether they had health insurance. Even among adults who had health insurance and ≥10 physician contacts during the preceding year, depending on the vaccine, 20.1%–87.5% reported not having received vaccinations that were recommended either for all persons or for those with specific indications. Overall, vaccination coverage among U.S.-born adults was significantly higher than that of foreign-born adults, including influenza vaccination (aged ≥19 years), pneumococcal vaccination (all ages), tetanus vaccination (all ages), Tdap vaccination (all ages), hepatitis B vaccination (aged ≥19 years and 19–49 years and travelers aged ≥19 years), herpes zoster vaccination (all ages), and HPV vaccination among females aged 19–26 years. Vaccination coverage also varied by citizenship status and years living in the United States. INTERPRETATION: NHIS data indicate that many adults remain unprotected against vaccine-preventable diseases. Coverage for the adult age-appropriate composite measures was low in all age groups. Individual adult vaccination coverage remained low as well, but modest gains occurred in vaccination coverage for hepatitis B (among adults aged ≥19 years and HCP aged ≥19 years), and HPV (among males aged 19–26 years and Hispanic females aged 19–26 years). Coverage for other vaccines and groups with Advisory Committee on Immunization Practices vaccination indications did not improve from 2017. Although HPV vaccination coverage among males aged 19–26 years and Hispanic females aged 19–26 years increased, approximately 50% of females aged 19–26 years and 70% of males aged 19–26 years remained unvaccinated. Racial/ethnic vaccination differences persisted for routinely recommended adult vaccines. Having health insurance coverage, having a usual place for health care, and having ≥1 physician contacts during the preceding 12 months were associated with higher vaccination coverage; however, these factors alone were not associated with optimal adult vaccination coverage, and findings indicate missed opportunities to vaccinate remained. PUBLIC HEALTH ACTIONS: Substantial improvement in adult vaccination uptake is needed to reduce the burden of vaccine-preventable diseases. Following the Standards for Adult Immunization Practice (https://www.cdc.gov/vaccines/hcp/adults/for-practice/standards/index.html), all providers should routinely assess adults’ vaccination status at every clinical encounter, strongly recommend appropriate vaccines, either offer needed vaccines or refer their patients to another provider who can administer the needed vaccines, and document vaccinations received by their patients in an immunization information system. | MMWR Surveill Summ | 2021 | CORD-19 | |
| 691 | Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study Summary Background Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures. Methods From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk. Findings Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20–22). Cases were isolated on average 4·6 days (95% CI 4·1–5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1–2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49–26·33] for household contacts and 7·06 [1·43–34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1–13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3–0·5), with a mean serial interval of 6·3 days (95% CI 5·2–7·6). Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. Funding Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention. | Lancet Infect Dis | 2020 | LitCov and CORD-19 | |
| 692 | Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies N/A | Biosci Trends | 2020 | LitCov and CORD-19 | |
| 693 | SARS-CoV-2 Pandemic: Should Children Wear Masks? N/A | Acta Med Port | 2020 | LitCov and CORD-19 | |
| 694 | Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain relevant expertise spanning NIBS technology, clinical services, and basic and clinical research – with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk. | Brain Stimul | 2020 | LitCov and CORD-19 | |
| 695 | Predictive role of clinical features in patients with COVID-19 for severe disease N/A | Zhong Nan Da Xue Xue Bao Yi Xu | 2020 | LitCov and CORD-19 | |
| 696 | Broad and Differential Animal Angiotensin-Converting Enzyme 2 Receptor Usage by SARS-CoV-2 The COVID-19 pandemic has caused an unprecedented global public health and economic crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, unlike the SARS-CoV-2-like coronaviruses (CoVs) identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2s from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site-deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activities, respectively. Among the remaining species, ACE2s from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models. IMPORTANCE SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2. | J Virol | 2020 | LitCov and CORD-19 | |
| 697 | Machine Learning to Predict Mortality and Critical Events in a Cohort of Patients With COVID-19 in New York City: Model Development and Validation BACKGROUND: COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking. OBJECTIVE: The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points. METHODS: We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19–positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions. RESULTS: Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction. CONCLUSIONS: We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes. | J Med Internet Res | 2020 | LitCov and CORD-19 | |
| 698 | A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)(1,2,3,4,5), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature02463) contains supplementary material, which is available to authorized users. | Nature | 2004 | CORD-19 | |
| 699 | Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease: a multicenter European study OBJECTIVE: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. METHODS: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). CONCLUSION: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00405-020-05965-1) contains supplementary material, which is available to authorized users. | Eur Arch Otorhinolaryngol | 2020 | LitCov and CORD-19 | |
| 700 | Coronavirus Infection in Acute Lower Respiratory Tract Disease of Infants A serologic surveillance of lower respiratory tract disease in 417 hospitalized children under 18 months of age revealed infection with coronaviruses (strains OC43 and/or 229E) in 34 (8.2%). During the same interval, one of 13 control infants was infected. There were two distinct periods lasting six and 14 weeks, respectively, during which the incidence rose to as high as 18.9% of patients with lower respiratory tract disease. The incidence of coronavirus infection in patients with pneumonia and bronchiolitis was higher than the incidences of adenoviruses, influenza, parainfluenza viruses types 1 and 2, and rhinoviruses, and lower only than the incidences of parainfluenza virus type 3 and respiratory syncytial virus. Coronaviruses serologically similar or identical to strain 229E were recovered from frozen nasal washes obtained during the acute phase of pneumonia in two children. | J Infect Dis | 1974 | 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
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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.