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

BIP! Finder for COVID-19

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

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

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

Use:  Impact  Relevance & Impact
TitleVenueYearImpactSource
1351A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2  

The coronavirus spike (S) protein mediates infection of receptor-expressing host cells and is a critical target for antiviral neutralizing antibodies. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the coronavirus (severe acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate that a 193-amino acid fragment of the S protein (residues 318–510) bound ACE2 more efficiently than did the full S1 domain (residues 12–672). Smaller S protein fragments, expressing residues 327–510 or 318–490, did not detectably bind ACE2. A point mutation at aspartic acid 454 abolished association of the full S1 domain and of the 193-residue fragment with ACE2. The 193-residue fragment blocked S protein-mediated infection with an IC(50) of less than 10 nm, whereas the IC(50) of the S1 domain was ∼50 nm. These data identify an independently folded receptor-binding domain of the SARS-CoV S protein.

J Biol Chem2004       CORD-19
1352Neutrophil extracellular traps in COVID-19  

N/A

JCI Insight2020       LitCov and CORD-19
1353In silico validation of coumarin derivatives as potential inhibitors against Main Protease, NSP10/NSP16-Methyltransferase, Phosphatase and Endoribonuclease of SARS CoV-2  

Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus was named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), (Coronavirus Disease 2019). Currently, there is no specific drug for the therapy of COVID-19. So, there is a need to develop or find out the new drug from the existing to cure the COVID-19. Identification of a potent inhibitor of Methyltransferase, Endoribonuclease, Phosphatase and Main Protease enzymes of SARS CoV-2 by coumarin derivatives using insilico approach. The in silico studies were performed on maestro 12.0 software (Schrodinger LLC 2019, USA). Two thousand seven hundred fifty-five biologically active coumarin derivative was docked with above receptor proteins of SARS CoV-2. The molecular dynamic simulation of the top one ligand of respected proteins was performed. Top five ligands of each protein were taken for study. Coumarin derivatives actively interact with taken receptors and showed good docking results for Methyltransferase, Endoribonuclease, Phosphatase and Main Protease and top five compounds of each have docking score from –9.00 to –7.97, –8.42 to –6.80, –8.63 to –7.48 and –7.30 to –6.01 kcal/mol, respectively. The docked compounds were showed RMSD and binding stability of simulated ligands are show the potency of ligands against the SARS CoV-2. Our study provides information on drugs that may be a potent inhibitor of COVID-19 infection. Drug repurposing of the available drugs would be great help in the treatment of COVID-19 infection. The combination therapy of the finding may improve inhibitory activity. Communicated by Ramaswamy H. Sarma HIGHLIGHTS: Coronavirus Disease (COVID-19) is recently declared pandemic (WHO) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In silico virtual screening, docking, ADME, MM-GBSA and MD simulation analysis of coumarin derivatives against Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and Main Protease enzyme of SARS CoV-2. All the analysis was performed on Maestro 12.0 Schrodinger software against respective receptors. Top five compounds of coumarin derivatives s docked at the active site of Methyltransferase (MTase), Endoribonuclease(endoU), ADP ribose Phosphatase and protease and top five compounds of each have docking score from –9.00 to –7.97, –8.42 to –6.80, –8.63 to –7.48 and –7.30 to –6.01 kcal/mol, respectively, of SARS CoV-2. These compounds were used to analysis of binding free energy by using the Prime MM-GBSA module. All the compounds showed drug-likeness properties. MD simulation of Proteins and ligands showed binding stability and good RMSD, radius of gyration of protein, coulomb-SR and LJ-SR energy.

J Biomol Struct Dyn2020       LitCov and CORD-19
1354Effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study  

BACKGROUND: The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures—including novel digital tracing approaches and less intensive physical distancing—might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. METHODS: For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40 162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. RESULTS: We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15 000–41 000 contacts would be newly quarantined each day. INTERPRETATION: Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. FUNDING: Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council.

Lancet Infect Dis2020       LitCov and CORD-19
1355The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase  

Abstract The 5′-most gene, gene 1, of the genome of murine coronavirus, mouse hepatitis virus (MHV), is presumed to encode the viral RNA-dependent RNA polymerase. We have determined the complete sequence of this gene of the JHM strain by cDNA cloning and sequencing. The total length of this gene is 21,798 nucleotides long, which includes two overlapping, large open reading frames. The first open reading frame, ORF 1 a, is 4488 amino acids long. The second open reading frame, ORF 1 b, overlaps ORF 1 a for 75 nucleotides, and is 2731 amino acids long. The overlapping region may fold into a pseudoknot RNA structure, similar to the corresponding region of the RNA of avian coronavirus, infectious bronchitis virus (IBV). The in vitro transcription and translation studies of this region indicated that these two ORFs were most likely translated into one polyprotein by a ribosomal frameshifting mechanism. Thus, the predicted molecular weight of the gene 1 product is more than 800,000 Da. The sequence of ORF 1 b is very similar to the corresponding ORF of IBV. In contrast, the ORF 1 a of these two viruses differ in size and have a high degree of divergence. The amino acid sequence analysis suggested that ORF 1 a contains several functional domains, including two hydrophobic, membrane-anchoring domains, and three cysteine-rich domains. It also contains a picornaviral 3C-like protease domain and two papain-like protease domains. The presence of these protease domains suggests that the polyprotein is most likely processed into multiple protein products. In contrast, the ORF 1b contains polymerase, helicase, and zinc-finger motifs. These sequence studies suggested that the MHV gene 1 product is involved in RNA synthesis, and that this product is processed autoproteolytically after translation. This study completes the sequence of the MHV genome, which is 31 kb long, and constitutes the largest viral RNA known.

Virology1991       CORD-19
1356Air, Surface Environmental and Personal Protective Equipment Contamination by SARS-CoV-2 From a Symptomatic Patient  

N/A

JAMA2020       LitCov and CORD-19
1357Social Media and Research Publication Activity During Early Stages of the COVID-19 Pandemic: Longitudinal Trend Analysis  

BACKGROUND: The COVID-19 pandemic has highlighted the importance of rapid dissemination of scientific and medical discoveries. Current platforms available for the distribution of scientific and clinical research data and information include preprint repositories and traditional peer-reviewed journals. In recent times, social media has emerged as a helpful platform to share scientific and medical discoveries. OBJECTIVE: This study aimed to comparatively analyze activity on social media (specifically, Twitter) and that related to publications in the form of preprint and peer-reviewed journal articles in the context of COVID-19 and gastroenterology during the early stages of the COVID-19 pandemic. METHODS: COVID-19–related data from Twitter (tweets and user data) and articles published in preprint servers (bioRxiv and medRxiv) as well as in the PubMed database were collected and analyzed during the first 6 months of the pandemic, from December 2019 through May 2020. Global and regional geographic and gastrointestinal organ–specific social media trends were compared to preprint and publication activity. Any relationship between Twitter activity and preprint articles published and that between Twitter activity and PubMed articles published overall, by organ system, and by geographic location were identified using Spearman’s rank-order correlation. RESULTS: Over the 6-month period, 73,079 tweets from 44,609 users, 7164 journal publications, and 4702 preprint publications were retrieved. Twitter activity (ie, number of tweets) peaked in March 2020, whereas preprint and publication activity (ie, number of articles published) peaked in April 2020. Overall, strong correlations were identified between trends in Twitter activity and preprint and publication activity (P<.001 for both). COVID-19 data across the three platforms mainly concentrated on pulmonology or critical care, but when analyzing the field of gastroenterology specifically, most tweets pertained to pancreatology, most publications focused on hepatology, and most preprints covered hepatology and luminal gastroenterology. Furthermore, there were significant positive associations between trends in Twitter and publication activity for all gastroenterology topics (luminal gastroenterology: P=.009; hepatology and inflammatory bowel disease: P=.006; gastrointestinal endoscopy: P=.007), except pancreatology (P=.20), suggesting that Twitter activity did not correlate with publication activity for this topic. Finally, Twitter activity was the highest in the United States (7331 tweets), whereas PubMed activity was the highest in China (1768 publications). CONCLUSIONS: The COVID-19 pandemic has highlighted the potential of social media as a vehicle for disseminating scientific information during a public health crisis. Sharing and spreading information on COVID-19 in a timely manner during the pandemic has been paramount; this was achieved at a much faster pace on social media, particularly on Twitter. Future investigation could demonstrate how social media can be used to augment and promote scholarly activity, especially as the world begins to increasingly rely on digital or virtual platforms. Scientists and clinicians should consider the use of social media in augmenting public awareness regarding their scholarly pursuits.

J Med Internet Res2021       LitCov and CORD-19
1358Impact of extracranial contamination on regional cerebral oxygen saturation: a comparison of three cerebral oximetry technologies  

N/A

Anesthesiology2012       CORD-19
1359COVID-19: A Systematic Review of Imaging Findings in 919 Patients  

N/A

AJR Am J Roentgenol2020       LitCov and CORD-19
1360Putative papain-related thiol proteases of positive-strand RNA viruses Identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, alpha- and coronaviruses  

Abstract A computer-assisted comparative analysis of the amino acid sequences of (putative) thiol proteases encoded by the genomes of several diverse groups or positive-stranded RNA viruses and distantly related to the family of cellular papain-like proteases is presented. A high level of similarity was detected between the leader protease of foot-and-mouth-disease virus and the protease of murine hepatitis coronavirus which cleaves the N-terminal p28 protein from the polyprotein. Statistically significant alignment of a portion of the rubella virus polyprotein with cellular papain-like proteases was obtained, leading to tentative identification of the papain-like protease as the enzyme mediating processing of the non-structural proteins of this virus. Specific grouping between the sequences of the proteases of α-viruses, and poty- and bymoviruses was revealed. It was noted that papain-like proteases of positive-stranded RNA viruses are much more variable both in their sequences and in genomic locations than chymotrypsin-related proteases found in the same virus class. A novel conserved domain of unknown function has also been identified which flanks the papain-like proteases of α-, rubi- and coronaviruses.

FEBS Lett1991       CORD-19
1361Reply to "Coronavirus Disease 19: Implications for Clinical Dental Care"  

J Endod2020       LitCov and CORD-19
1362SARS-CoV-2: a storm is raging  

N/A

J Clin Invest2020       LitCov and CORD-19
1363Genomic characterisation of the severe acute respiratory syndrome coronavirus of Amoy Gardens outbreak in Hong Kong  

Severe acute respiratory syndrome (SARS) is a global health concern. In Hong Kong, two major outbreaks, one hospital based and the other in the Amoy Gardens apartments, were identified. The frequency of diarrhoea, admission to intensive care, and mortality differed significantly between the two outbreaks. We did genomic sequencing for viral isolates from five Amoy Gardens patients. The virus sequence was identical in four of these five patients. The sequence data from one hospital case and the four identical community cases had only three nucleotide differences. Alterations in the SARS coronavirus genome are unlikely to have caused the distinctive clinical features of the Amoy Gardens patients, and these results highlight the importance of non-viral genomic factors in this outbreak.

Lancet2003       CORD-19
1364Rapid and sensitive method using multiplex real-time PCR for diagnosis of infections by influenza a and influenza B viruses, respiratory syncytial virus and parainfluenza viruses 1, 2, 3 and 4  

N/A

J Clin Microbiol2004       CORD-19
1365Transmission risk of SARS-CoV-2 to healthcare workers -observational results of a primary care hospital contact tracing  

N/A

Swiss Med Wkly2020       LitCov and CORD-19
1366Medical Student Education During the COVID-19 Pandemic: Initial Experiences Implementing a Virtual Interventional Radiology Elective Course  

RATIONALE AND OBJECTIVES: In response to the COVID-19 pandemic reducing medical student presence on clinical services and in classrooms, academic institutions are utilizing a virtual format to continue medical student education. We describe a successful initial experience implementing a virtual elective in interventional radiology (IR) and provide the course framework, student feedback, and potential improvements. MATERIAL AND METHODS: A two-week virtual IR elective curriculum was created utilizing a combination of synchronous and asynchronous learning and the “flipped” classroom educational model. Students virtually participated in daily IR resident education conferences, resident-led case review sessions, and dedicated lectures. Asynchronous pre-learning material consisted of text and video correlating to lecture topics. Anonymous pre-course and post-course surveys were sent to all participating students (n=10). RESULTS: Ten students (100%) completed pre-course and seven (70%) completed post-course surveys. Enrolled students were considering residencies in surgery (50%), internal medicine (40%), interventional radiology (30%), and/or diagnostic radiology (30%). Students’ understanding of what IRs do and the procedures they perform (p<0.001), when to consult IR for assistance in patient management (p=0.005), and the number of IR procedures students could recall (p=0.015) improved after the course. Case-review sessions and virtual lectures ranked as having the highest education value. Students recommended additional small-group case workshops. CONCLUSION: This successful virtual IR elective provides a framework for others to continue IR medical student education during the pandemic and grow the specialty's presence within an increasingly virtual medical school curriculum. The described model may be modified to improve IR education beyond the COVID-19 era.

Acad Radiol2020       LitCov and CORD-19
1367Subcutaneous Sarilumab in hospitalised patients with moderate-severe COVID-19 infection compared to the standard of care (SARCOVID): a structured summary of a study protocol for a randomised controlled trial  

OBJECTIVES: The main aim of the study is to evaluate the efficacy of a single dose of sarilumab, in subcutaneous administration, in hospitalised patients with moderate to early severe COVID-19 infection compared to the current standard of care, to prevent progression to systemic hyperinflammatory status. Our hypothesis is that use of subcutaneous sarilumab in early stages (window of opportunity) of COVID-19 moderate-severe pneumonia can prevent higher oxygenation requirements through non-invasive and invasive mechanical ventilation and decrease in-hospital stays, as well as death rate. The secondary objectives of the study are to evaluate the safety of sarilumab through hospitalisation and up to day 14 after discharge, compared to the control arm as assessed by incidence of serious and non serious adverse events (SAEs). In addition, as an exploratory objective, to compare the baseline clinical and biological parameters, including serum IL-6 levels, of the intervention population against controls of the same pandemic outbreak (using a propensity score) to search for markers that identify the best candidates for the treatment with subcutaneous IL-6R inhibitors and to attempt an approximation in the temporal frame of the “window of opportunity” TRIAL DESIGN: SARCOVID is an investigator-initiated single center randomised proof of concept study. PARTICIPANTS: Patients treated at the Hospital Universitario La Princesa, Madrid, Spain requiring hospitalisation will be consecutively recruited, meeting all inclusion criteria and none of the exclusion criteria Inclusion criteria a. Age >18, <80 years old b. COVID-19 infection documented by a positive RT-PCR test or, in absence of a RT-PCR positive test, case definition of COVID 19 infection/pneumonia as per local protocol and the presence of a positive serologic test (IgM/IgA by ELISA) c. Documented interstitial pneumonia requiring admission and at least two of the following parameters: 1) Fever ≥ 37.8°C (tympanic) 2) IL-6 in serum ≥ 25 pg/mL (in the absence of a previous dose of prednisone or equivalent> 1 mg / kg) or PCR> 5mg/dL 3) Lymphocytes <600 cells/mm(3) 4) Ferritin> 300 μg/L that doubles in 24 hours 5) Ferritin> 600 μg/L in the first determination and LDH> 250 U/L 6) D-dimer (> 1 mg/L) d. Informed verbal consent or requested under urgent conditions, documented in the electronic medical record. Exclusion criteria a. Patients who require mechanical ventilation at the time of inclusion. b. AST / ALT values > 5 folds the ULN. c. Absolute neutrophil count below 500 cells/mm(3) d. Absolute platelet count below 50,000 cells/mm(3) e. Documented sepsis or high suspicion of superimposed infection by pathogens other than COVID-19. f. Presence of comorbidities that can likely lead to an unfavourable result according to clinical judgment. g. Complicated diverticulitis or intestinal perforation. h. Current skin infection (eg, uncontrolled dermopiodermitis). i. Immunosuppressive anti-rejection therapy. j. Pregnancy or lactation. k. Previous treatment with tocilizumab or sarilumab. l. Patients participating in another clinical trial for SARS-CoV-2 infection. m. Patients with known hypersensitivity or contraindication to sarilumab or excipients. INTERVENTION AND COMPARATOR: The intervention group, sarilumab plus standard of care, will receive 400 mg single dose treatment with Sarilumab (Kevzara), 2 subcutaneous injections 200mg each in a pre-filled syringe. Treatment with drugs or procedures in routine clinical practice that the clinician responsible for the patient deems necessary is allowed. The control group will receive drugs or procedures in routine clinical practice according to the best standard of care as per local protocol. MAIN OUTCOMES: Primary Outcome Measures 1. Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation compared to baseline (Score ranges 1-7) 1. Death; 2. Hospitalised, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalised, requiring non-invasive ventilation or high flow oxygen devices; 4. Hospitalised, requiring supplemental oxygen; 5. Hospitalised, not requiring supplemental oxygen - but in need of ongoing medical care (COVID-19 related or otherwise) 6. Hospitalised, not requiring supplemental oxygen - no longer requires ongoing medical care (independent) 7. Not hospitalised 2. Duration of hospitalisation: Days from the date of enrolment to the date of discharge 3. Number of deaths at the end of study RANDOMISATION: Randomisation to treatment arms sarilumab plus standard of care or standard of care in a 2:1 ratio will be performed by the Clinical Research and Clinical Trials Unit (CRCTU) at the Hospital using a table of random numbers, an internet-based randomisation tool. After checking that all inclusion criteria are met and none of the exclusion criteria, CRCTU will communicate the recruiting investigator the assigned treatment. BLINDING (MASKING): This study is unblinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 30 patients treated by COVID-19 infection who require hospitalisation: 20 will receive sarilumab plus Standard of Care and 10 will receive Standard of Care. TRIAL STATUS: The Protocol version number is 2, as of 6(th) April 2020, with amendment 1, as of 7(th) May 2020. The recruitment is ongoing. Recruitment started on April 13(th) 2020 and is anticipated to be completed by November 2020. TRIAL REGISTRATION: This trial was first registered in the European Union Clinical Trials Register on 4 April 2020, EudraCT Number 2020-001634-36. Then, posted on ClinicalTrials.gov on 22 April 2020, Identifier: NCT04357808. 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. The study protocol has been reported in accordance with the International Council Harmonization guidelines: https://www.ich.org/page/efficacy-guidelines.

Trials2020       LitCov and CORD-19
1368Severe acute respiratory syndrome in children: experience in a regional hospital in Hong Kong  

N/A

Pediatr Crit Care Med2003       CORD-19
1369A pilot study of therapeutic plasma exchange for serious SARS CoV-2 disease: A structured summary of a randomized controlled trial study protocol  

OBJECTIVES: To evaluate the safety of therapeutic plasma exchange (TPE) in adult patients with serious/life-threatening COVID-19 requiring intensive care unit (ICU) admission, and associated 28-day mortality. Serious and life threatening COVID-19 are defined as per published literature (please, refer to the full protocol, Additional file 1). The rationale is that TPE can remove interleukins-3, 6, 8, 10, interferon-gamma and tumor necrosis factor-alpha. Thus, it may reduce the cytokine release syndrome associated with fulminant COVID-19 disease. TRIAL DESIGN: Pilot, interventional, open-label, randomized controlled multicenter trial. PARTICIPANTS: Inclusion criteria are: 1) age ≥ 18 years old; 2) intubation and intensive care unit (ICU) admission; 3) serious and/or life-threatening COVID-19 (please, refer to the full protocol, Additional file 1). SARS-CoV-2 infection is confirmed by Real-Time-Polymerase-Chain-Reaction (RT-PCR) assays using QuantiNova Probe RT-PCR kit (Qiagen) in a Light-Cycler 480 real-time PCR system (Roche, Basel, Switzerland). Exclusion criteria are: 1) previous allergic reaction to plasma exchange or its ingredients (i.e., sodium citrate), 2) two consecutive negative RT-PCR tests for SARS-CoV-2 at least 24 hours apart, 3) mild COVID-19 not requiring ICU admission and 4) terminally ill patients receiving palliative care. The primary site will be King Saud Medical City (KSMC), Riyadh, Kingdom of Saudi Arabia (KSA). Also, the study will run in ICUs (Ministry of Health Cluster 1; Riyadh) and other centers in KSA pending their institutional review board (IRB) approval. INTERVENTIONS AND COMPARATOR: The intervention group will receive TPE, plus empiric treatment for COVID-19. TPE is administered using the Spectra Optia TM Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA). The first dose is 1.5 plasma volumes, followed by one plasma volume on alternate days or daily for five to seven total treatments. Spectra Optia TM Apheresis System operates with acid-citrate dextrose anticoagulant (ACDA) as per Kidney Disease Improving Global Outcomes (KDIGO) 2019 guidelines. Plasma is replaced with albumin 5% or fresh frozen plasma in patients with coagulopathy (prothrombin time >37 seconds; international normalized ratio >3; activated partial thromboplastin time >100 or fibrinogen level <100 mg/d). TPE sessions are performed daily over four hours and laboratory markers measured daily. The comparators are controls not receiving TPE but usual empiric treatment for COVID-19 as per institutional, national and international recommendations. Both groups will receive standard ICU supportive care. MAIN OUTCOMES: Primary study end-point is 28-day mortality and safety of TPE in serious and/or life-threatening COVID-19. Safety will be evaluated by the documentation of any pertinent adverse and/or serious adverse effects related to TPE as per institutional, national and international (Food and Drug Administration) guidelines. Secondary outcomes are: i) improvement in Sequential Organ Function Assessment (SOFA) score ; ii) changes in inflammatory markers: serum C-reactive protein, lactate dehydrogenase, ferritin, d-dimers and interleukin-6; iii) days on mechanical ventilation and ICU length of stay. RANDOMIZATION: Eligible consented patients are randomized (1:1 allocation) after stratification by ICU center and two PaO2/FIO2 ratio categories (> 150 and ≤ 150). Randomization occurs in variable block sizes of four to eight patients. A web-based randomization service, randomize.net, is used to allocate patients to their respective strata prior to the intervention or control therapy. BLINDING (MASKING): Given the visibility of TPE machinery, the intervention will be unblinded; hence, no enrollment concealment will be expedited. The lack of allocation concealment will be mitigated by several measures (please, refer to the full protocol, Additional file 1). NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This pilot randomized trial aims to recruit a convenience sample of patients with serious and/or life-threatening COVID-19. Therefore, at least 20 patients are to be randomized to each group per participating center. We are hoping to consent and randomize approximately 60 patients in each group over a 3 to 6 months period giving a total of 120 participants. TRIAL STATUS: The protocol version 1 was approved 29/04/2020. Recruitment is ongoing, and began on 01/05/2020. We estimate completion by 29/10/2020. TRIAL REGISTRATION: Registered at ISRCTN on 18/05/2020 (ISRCTN21363594; doi.10.1186/ ISRCTN21363594). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Trials2020       LitCov and CORD-19
1370From People to Panthera: Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo  

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.

mBio2020       LitCov and CORD-19
1371Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection: A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatient  

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Arm 1: Control arm. Arms 2 to 5: Experimental treatment arms. Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8(th), 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8(th), 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15(th), 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15(th), 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22(nd), 2020 (Identifier: NCT04356495): and on EudraCT on April 10(th), 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Trials2020       LitCov and CORD-19
1372Clinical characteristics and prognosis of 33 children with severe acute respiratory syndrome in Guangzhou area  

N/A

Zhonghua Er Ke Za Zhi2003       CORD-19
1373Neonatal outcome in 29 pregnant women with COVID-19: A retrospective study in Wuhan, China  

BACKGROUND: As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed pregnant women with COVID-19 had similar clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women. METHODS AND FINDINGS: In this retrospective study, we studied 29 pregnant women with COVID-19 infection delivered in 2 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates. Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free. Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery. Of 30 neonates, 18 were admitted to Wuhan Children’s Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiological features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups. CONCLUSIONS: In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031954 (Maternal and Perinatal Outcomes of Women with coronavirus disease 2019 (COVID-19): a multicenter retrospective cohort study).

PLoS Med2020       LitCov and CORD-19
1374Function of HAb18G/CD147 in Invasion of Host Cells by Severe Acute Respiratory Syndrome Coronavirus  

To identify the function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome (SARS) coronavirus (CoV), we analyzed the protein-protein interaction among HAb18G/CD147, cyclophilin A (CyPA), and SARS-CoV structural proteins by coimmunoprecipitation and surface plasmon resonance analysis. Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147. Further research showed that HAb18G/CD147, a transmembrane molecule, was highly expressed on 293 cells and that CyPA was integrated with SARS-CoV. HAb18G/CD147–antagonistic peptide (AP)–9, an AP of HAb18G/CD147, had a high rate of binding to 293 cells and an inhibitory effect on SARS-CoV. These results show that HAb18G/CD147, mediated by CyPA bound to SARS-CoV N protein, plays a functional role in facilitating invasion of host cells by SARS-CoV. Our findings provide some evidence for the cytologic mechanism of invasion by SARS-CoV and provide a molecular basis for screening anti-SARS drugs

J Infect Dis2005       CORD-19
1375The psychological impact of COVID-19 pandemic on Healthcare workers in a MERS-CoV endemic country  

BACKGROUND: The global pandemic of coronavirus disease of 2019 (COVID-19) has led to unprecedented psychological stress on health workers (HCWs). We aimed to assess the psychological impact of COVID-19 on HCWs in comparison to the stress brought on by the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic in Saudi Arabia. METHOD: Between February 5th and 16th, 2020, 811 health-care workers (HCWs) of a tertiary care teaching hospital were invited to fill a questionnaire regarding concerns and worries about the novel coronavirus pandemic, along with Generalized Anxiety Disorder (GAD-7) Anxiety Severity screening tool. RESULTS: Out of 582 HCWs who completed the survey questionnaire (response rate of 71.8%), about 40% were exposed previously to MERS-CoV infected or suspected patients during a previous hospital outbreak. While there were no COVID-19 cases reported yet in Saudi Arabia at the time of data collection, still, the anxiety level from COVID-19 was significantly higher than that from MERS-CoV or seasonal influenza: 41.1% were more worried about COVID-19, 41.4% were similarly worried about both MERS-CoV and COVID-19, and 17.5% were more stressed by the previous MERS-CoV hospital outbreak. The most frequent concern was transmitting the infection to family and friends (2.71/5) than to themselves only (2.57/5). CONCLUSION: Pandemic and epidemic infectious diseases such as COVID-19 or MERS-CoV impose a significant level of anxiety and stress on healthcare workers who are caring of infected patients, with their main concern being the risk of transmitting the infection to their families or to acquire it themselves. Therefore, optimizing the compliance of healthcare workers with the proper infection prevention and control measures is paramount during the infectious disease outbreak, to ensure their safety, to decrease the likelihood of getting infected or transmitting the infection to others, and consequently to alleviate their psychological stress and anxiety.

J Infect Public Health2020       LitCov and CORD-19
1376Mental wellbeing in the German old age population largely unaltered during COVID-19 lockdown: results of a representative survey  

BACKGROUND: Older individuals are at increased risk of a severe and lethal course of COVID-19. They have typically been advised to practice particularly restrictive social distancing (‘cocooning’), which has sparked much debate on the consequences for their mental wellbeing. We aimed to provide evidence by conducting a representative survey among the German old population during COVID-19 lockdown. METHODS: A computer-assisted standardized telephone interview was conducted in a randomly selected and representative sample of the German old age population (n = 1005; age ≥ 65 years) during the first lockdown in April 2020. Assessments included sociodemographic factors, aspects of the personal life situation during lockdown, attitudes towards COVID-19, and standardized screening measures on depression, anxiety, somatization, overall psychological distress (Brief Symptom Inventory/BSI-18) and loneliness (UCLA 3-item loneliness scale). Sampling-weighted descriptive statistics and multiple multivariable regression analyses were conducted. RESULTS: Participants were M = 75.5 (SD = 7.1) years old; 56.3% were women. At data collection, COVID-19 lockdown had been in force for M = 28.0 (SD = 4.8) days. Overall, older individuals were worried about COVID-19, but supportive of the lockdown. Mean BSI-18 scores were 1.4 for depression, 1.6 for anxiety and 2.2 for somatization as well as 5.1 for global psychological distress. These figures did not indicate worse mental wellbeing, given normative values established by studies before the pandemic (2.0, 1.6, 2.4, 6.0, respectively). The prevalence of loneliness was 13.1%, which also fell within a range of estimates reported by studies before the pandemic. There were only few significant associations of aspects of the personal life situation during lockdown and attitudes towards COVID-19 with mental wellbeing. Resilience explained a large amount of variance. CONCLUSIONS: In the short-term, the mental wellbeing of the German old age population was largely unaltered during COVID-19 lockdown, suggesting resilience against the challenging pandemic situation. Our results refute common ageist stereotypes of “the weak and vulnerable older adults” that were present during the pandemic. Long-term observations are needed to provide robust evidence. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-020-01889-x.

BMC Geriatr2020       LitCov and CORD-19
1377The pivotal link between ACE2 deficiency and SARS-CoV-2 infection  

Abstract Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7. In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.

Eur J Intern Med2020       LitCov and CORD-19
1378Preparedness among Ophthalmologists: During and Beyond the COVID-19 Pandemic  

Ophthalmology2020       LitCov and CORD-19
1379Agile Requirements Engineering and Software Planning for a Digital Health Platform to Engage the Effects of Isolation Caused by Social Distancing: Case Study  

BACKGROUND: Social distancing and shielding measures have been put in place to reduce social interaction and slow the transmission of the coronavirus disease (COVID-19). For older people, self-isolation presents particular challenges for mental health and social relationships. As time progresses, continued social distancing could have a compounding impact on these concerns. OBJECTIVE: This project aims to provide a tool for older people and their families and peers to improve their well-being and health during and after regulated social distancing. First, we will evaluate the tool’s feasibility, acceptability, and usability to encourage positive nutrition, enhance physical activity, and enable virtual interaction while social distancing. Second, we will be implementing the app to provide an online community to assist families and peer groups in maintaining contact with older people using goal setting. Anonymized data from the app will be aggregated with other real-world data sources to develop a machine learning algorithm to improve the identification of patients with COVID-19 and track for real time use by health systems. METHODS: Development of this project is occurring at the time of publication, and therefore, a case study design was selected to provide a systematic means of capturing software engineering in progress. The app development framework for software design was based on agile methods. The evaluation of the app’s feasibility, acceptability and usability shall be conducted using Public Health England's guidance on evaluating digital health products, Bandura’s model of health promotion, the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework and the Nonadoption, Abandonment and Challenges to the Scale-up, Spread and Suitability (NASSS) framework. RESULTS: Making use of a pre-existing software framework for health behavior change, a proof of concept was developed, and a multistage app development and deployment for the solution was created. Grant submissions to fund the project and study execution have been sought at the time of publication, and prediscovery iteration of the solution has begun. Ethical approval for a feasibility study design is being sought. CONCLUSIONS: This case study lays the foundations for future app development to combat mental and societal issues arising from social distancing measures. The app will be tested and evaluated in future studies to allow continuous improvement of the app. This novel contribution will provide an evidence-based exemplar for future app development in the space of social isolation and loneliness.

JMIR Public Health Surveill2020       LitCov and CORD-19
1380Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients  

PURPOSE: The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. METHODS: From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. RESULTS: Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5–28) days since symptoms’ onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06–3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11–0.89, p = 0.029). CONCLUSION: Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.

Endocrine2020       LitCov and CORD-19
1381Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor  

N/A

J Virol2004       CORD-19
1382Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission  

Summary Background Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital. Methods Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV. Findings Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9–12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure. Interpretation Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor. Funding French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.

Lancet2013       CORD-19
1383COVID-19 symptoms predictive of healthcare workers' SARS-CoV-2 PCR results  

BACKGROUND: Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. METHODS AND FINDINGS: We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9—April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARS-CoV-2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fifty-nine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10–3.64), which increased to 2.61 (95% CI: 1.50–4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature ≥ 37.5°C (3.49 (95% CI: 1.95–6.21)), and those with myalgias (1.83 (95% CI: 1.04–3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95–17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8–99.0%) for the exclusion of clinically relevant COVID-19. CONCLUSIONS: Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays.

PLoS One2020       LitCov and CORD-19
1384Maxillofacial services in the COVID-19 pandemic-early lessons from the Italian experience  

Br J Oral Maxillofac Surg2020       LitCov and CORD-19
1385Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients  

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

Science2020       LitCov and CORD-19
1386Routine laboratory testing to determine if a patient has COVID-19  

BACKGROUND: Specific diagnostic tests to detect severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and resulting COVID‐19 disease are not always available and take time to obtain results. Routine laboratory markers such as white blood cell count, measures of anticoagulation, C‐reactive protein (CRP) and procalcitonin, are used to assess the clinical status of a patient. These laboratory tests may be useful for the triage of people with potential COVID‐19 to prioritize them for different levels of treatment, especially in situations where time and resources are limited. OBJECTIVES: To assess the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID‐19. SEARCH METHODS: On 4 May 2020 we undertook electronic searches in the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions. SELECTION CRITERIA: We included both case‐control designs and consecutive series of patients that assessed the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID‐19. The reference standard could be reverse transcriptase polymerase chain reaction (RT‐PCR) alone; RT‐PCR plus clinical expertise or and imaging; repeated RT‐PCR several days apart or from different samples; WHO and other case definitions; and any other reference standard used by the study authors. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each included study. They also assessed the methodological quality of the studies, using QUADAS‐2. We used the 'NLMIXED' procedure in SAS 9.4 for the hierarchical summary receiver operating characteristic (HSROC) meta‐analyses of tests for which we included four or more studies. To facilitate interpretation of results, for each meta‐analysis we estimated summary sensitivity at the points on the SROC curve that corresponded to the median and interquartile range boundaries of specificities in the included studies. MAIN RESULTS: We included 21 studies in this review, including 14,126 COVID‐19 patients and 56,585 non‐COVID‐19 patients in total. Studies evaluated a total of 67 different laboratory tests. Although we were interested in the diagnotic accuracy of routine tests for COVID‐19, the included studies used detection of SARS‐CoV‐2 infection through RT‐PCR as reference standard. There was considerable heterogeneity between tests, threshold values and the settings in which they were applied. For some tests a positive result was defined as a decrease compared to normal vaues, for other tests a positive result was defined as an increase, and for some tests both increase and decrease may have indicated test positivity. None of the studies had either low risk of bias on all domains or low concerns for applicability for all domains. Only three of the tests evaluated had a summary sensitivity and specificity over 50%. These were: increase in interleukin‐6, increase in C‐reactive protein and lymphocyte count decrease. Blood count Eleven studies evaluated a decrease in white blood cell count, with a median specificity of 93% and a summary sensitivity of 25% (95% CI 8.0% to 27%; very low‐certainty evidence). The 15 studies that evaluated an increase in white blood cell count had a lower median specificity and a lower corresponding sensitivity. Four studies evaluated a decrease in neutrophil count. Their median specificity was 93%, corresponding to a summary sensitivity of 10% (95% CI 1.0% to 56%; low‐certainty evidence). The 11 studies that evaluated an increase in neutrophil count had a lower median specificity and a lower corresponding sensitivity. The summary sensitivity of an increase in neutrophil percentage (4 studies) was 59% (95% CI 1.0% to 100%) at median specificity (38%; very low‐certainty evidence). The summary sensitivity of an increase in monocyte count (4 studies) was 13% (95% CI 6.0% to 26%) at median specificity (73%; very low‐certainty evidence). The summary sensitivity of a decrease in lymphocyte count (13 studies) was 64% (95% CI 28% to 89%) at median specificity (53%; low‐certainty evidence). Four studies that evaluated a decrease in lymphocyte percentage showed a lower median specificity and lower corresponding sensitivity. The summary sensitivity of a decrease in platelets (4 studies) was 19% (95% CI 10% to 32%) at median specificity (88%; low‐certainty evidence). Liver function tests The summary sensitivity of an increase in alanine aminotransferase (9 studies) was 12% (95% CI 3% to 34%) at median specificity (92%; low‐certainty evidence). The summary sensitivity of an increase in aspartate aminotransferase (7 studies) was 29% (95% CI 17% to 45%) at median specificity (81%) (low‐certainty evidence). The summary sensitivity of a decrease in albumin (4 studies) was 21% (95% CI 3% to 67%) at median specificity (66%; low‐certainty evidence). The summary sensitivity of an increase in total bilirubin (4 studies) was 12% (95% CI 3.0% to 34%) at median specificity (92%; very low‐certainty evidence). Markers of inflammation The summary sensitivity of an increase in CRP (14 studies) was 66% (95% CI 55% to 75%) at median specificity (44%; very low‐certainty evidence). The summary sensitivity of an increase in procalcitonin (6 studies) was 3% (95% CI 1% to 19%) at median specificity (86%; very low‐certainty evidence). The summary sensitivity of an increase in IL‐6 (four studies) was 73% (95% CI 36% to 93%) at median specificity (58%) (very low‐certainty evidence). Other biomarkers The summary sensitivity of an increase in creatine kinase (5 studies) was 11% (95% CI 6% to 19%) at median specificity (94%) (low‐certainty evidence). The summary sensitivity of an increase in serum creatinine (four studies) was 7% (95% CI 1% to 37%) at median specificity (91%; low‐certainty evidence). The summary sensitivity of an increase in lactate dehydrogenase (4 studies) was 25% (95% CI 15% to 38%) at median specificity (72%; very low‐certainty evidence). AUTHORS' CONCLUSIONS: Although these tests give an indication about the general health status of patients and some tests may be specific indicators for inflammatory processes, none of the tests we investigated are useful for accurately ruling in or ruling out COVID‐19 on their own. Studies were done in specific hospitalized populations, and future studies should consider non‐hospital settings to evaluate how these tests would perform in people with milder symptoms.

Cochrane Database Syst Rev2020       LitCov and CORD-19
1387Pressure-controlled vs volume-controlled ventilation for acute respiratory failure due to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)  

N/A

Cochrane Database Syst Rev2015       CORD-19
1388Does the COVID-19 pandemic impact parents' and adolescents' well-being? An EMA-study on daily affect and parenting  

Due to the COVID- 19 outbreak in the Netherlands (March 2020) and the associated social distancing measures, families were enforced to stay at home as much as possible. Adolescents and their families may be particularly affected by this enforced proximity, as adolescents strive to become more independent. Yet, whether these measures impact emotional well-being in families with adolescents has not been examined. In this ecological momentary assessment study, we investigated if the COVID-19 pandemic affected positive and negative affect of parents and adolescents and parenting behaviors (warmth and criticism). Additionally, we examined possible explanations for the hypothesized changes in affect and parenting. To do so, we compared daily reports on affect and parenting that were gathered during two periods of 14 consecutive days, once before the COVID-19 pandemic (2018–2019) and once during the COVID-19 pandemic. Multilevel analyses showed that only parents’ negative affect increased as compared to the period before the pandemic, whereas this was not the case for adolescents’ negative affect, positive affect and parenting behaviors (from both the adolescent and parent perspective). In general, intolerance of uncertainty was linked to adolescents’ and parents’ negative affect and adolescents’ positive affect. However, Intolerance of uncertainty, nor any pandemic related characteristics (i.e. living surface, income, relatives with COVID-19, hours of working at home, helping children with school and contact with COVID-19 patients at work) were linked to the increase of parents’ negative affect during COVID-19. It can be concluded that on average, our sample (consisting of relatively healthy parents and adolescents) seems to deal fairly well with the circumstances. The substantial heterogeneity in the data however, also suggest that whether or not parents and adolescents experience (emotional) problems can vary from household to household. Implications for researchers, mental health care professionals and policy makers are discussed.

PLoS One2020       LitCov and CORD-19
1389COVID-19: A Perspective from China  

In December 2019, an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurred in Wuhan, Hubei Province, China and spread across China and beyond. On February 12, 2020, WHO officially named the disease caused by the novel coronavirus as Coronavirus Disease 2019 (COVID-19). Since most COVID-19 infected patients were diagnosed with pneumonia and characteristic CT imaging patterns, radiological examinations have become vital in early diagnosis and assessment of disease course. To date, CT findings have been recommended as major evidence for clinical diagnosis of COVID-19 in Hubei, China. This review focuses on the etiology, epidemiology, and clinical symptoms of COVID-19, while highlighting the role of chest CT in prevention and disease control. A full translation of this article in Chinese is available in the supplement. - 请见䃼充资料阅读文章中文版∘

Radiology2020       LitCov and CORD-19
1390The effect of human mobility and control measures on the COVID-19 epidemic in China  

The ongoing COVID-19 outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions have been undertaken to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19.

Science2020       LitCov and CORD-19
1391Severe acute respiratory syndrome and influenza: virus incursions from southern China  

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Am J Respir Crit Care Med2003       CORD-19
1392Infectious diseases. Hungry for details, scientists zoom in on SARS genomes  

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Science2003       CORD-19
1393Alcohol use and mental health status during the first months of COVID-19 pandemic in Australia  

BACKGROUND: We aimed to estimate the population prevalence of people with changes in their usual patterns of alcohol use during the early stages of the novel coronavirus pandemic of 2020 (COVID-19) pandemic in Australia; assess the association between mental health status and changes in alcohol use during the pandemic; and examine if the associations were modified by gender and age. METHODS: This study was an anonymously-completed online self-report survey. Changes in alcohol use were assessed using a single fixed-choice study-specific question. Mental health was assessed using the Patient Health Questionnaire 9 and the Generalised Anxiety Disorder Scale. RESULTS: A total of 13,829 people contributed complete data and were included in the analysis. Overall, about one in five adults reported that they had been drinking more alcohol since the COVID-19 pandemic began than they used to. People were more likely to be drinking alcohol more than they used to if they had more severe symptoms of depression or anxiety. The associations between depressive and anxiety symptoms and increased alcohol use since the COVID-19 pandemic began were consistent between females and males. LIMITATIONS: Online surveys are less accessible to some groups of people. The data are self-report and not diagnostic. Cross-sectional data can identify associations, not causal relationships. The study was limited to participants from Australia. CONCLUSIONS: These data indicate that there is a need for public policies focused on alcohol use during the COVID-19 pandemic and the strategies should include specific consideration of the needs of people with mental health problems.

J Affect Disord2020       LitCov and CORD-19
1394Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury  

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.

Sci China Life Sci2020       LitCov and CORD-19
1395Association Between What People Learned About COVID-19 Using Web Searches and Their Behavior Towards Public Health Guidelines: Empirical Infodemiology Study  

BACKGROUND: The use of the internet and web-based platforms to obtain public health information and manage health-related issues has become widespread in this digital age. The practice is so pervasive that the first reaction to obtaining health information is to “Google it.” As SARS-CoV-2 broke out in Wuhan, China, in December 2019 and quickly spread worldwide, people flocked to the internet to learn about the novel coronavirus and the disease, COVID-19. Lagging responses by governments and public health agencies to prioritize the dissemination of information about the coronavirus outbreak through the internet and the World Wide Web and to build trust gave room for others to quickly populate social media, online blogs, news outlets, and websites with misinformation and conspiracy theories about the COVID-19 pandemic, resulting in people’s deviant behaviors toward public health safety measures. OBJECTIVE: The goals of this study were to determine what people learned about the COVID-19 pandemic through web searches, examine any association between what people learned about COVID-19 and behavior toward public health guidelines, and analyze the impact of misinformation and conspiracy theories about the COVID-19 pandemic on people’s behavior toward public health measures. METHODS: This infodemiology study used Google Trends’ worldwide search index, covering the first 6 months after the SARS-CoV-2 outbreak (January 1 to June 30, 2020) when the public scrambled for information about the pandemic. Data analysis employed statistical trends, correlation and regression, principal component analysis (PCA), and predictive models. RESULTS: The PCA identified two latent variables comprising past coronavirus epidemics (pastCoVepidemics: keywords that address previous epidemics) and the ongoing COVID-19 pandemic (presCoVpandemic: keywords that explain the ongoing pandemic). Both principal components were used significantly to learn about SARS-CoV-2 and COVID-19 and explained 88.78% of the variability. Three principal components fuelled misinformation about COVID-19: misinformation (keywords “biological weapon,” “virus hoax,” “common cold,” “COVID-19 hoax,” and “China virus”), conspiracy theory 1 (ConspTheory1; keyword “5G” or “@5G”), and conspiracy theory 2 (ConspTheory2; keyword “ingest bleach”). These principal components explained 84.85% of the variability. The principal components represent two measurements of public health safety guidelines—public health measures 1 (PubHealthMes1; keywords “social distancing,” “wash hands,” “isolation,” and “quarantine”) and public health measures 2 (PubHealthMes2; keyword “wear mask”)—which explained 84.7% of the variability. Based on the PCA results and the log-linear and predictive models, ConspTheory1 (keyword “@5G”) was identified as a predictor of people’s behavior toward public health measures (PubHealthMes2). Although correlations of misinformation (keywords “COVID-19,” “hoax,” “virus hoax,” “common cold,” and more) and ConspTheory2 (keyword “ingest bleach”) with PubHealthMes1 (keywords “social distancing,” “hand wash,” “isolation,” and more) were r=0.83 and r=–0.11, respectively, neither was statistically significant (P=.27 and P=.13, respectively). CONCLUSIONS: Several studies focused on the impacts of social media and related platforms on the spreading of misinformation and conspiracy theories. This study provides the first empirical evidence to the mainly anecdotal discourse on the use of web searches to learn about SARS-CoV-2 and COVID-19.

J Med Internet Res2021       LitCov and CORD-19
1396Nanobiosensors for the Detection of Novel Coronavirus 2019-nCoV and Other Pandemic/Epidemic Respiratory Viruses: A Review  

The coronavirus disease 2019 (COVID-19) pandemic is considered a public health emergency of international concern. The 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused this pandemic has spread rapidly to over 200 countries, and has drastically affected public health and the economies of states at unprecedented levels. In this context, efforts around the world are focusing on solving this problem in several directions of research, by: (i) exploring the origin and evolution of the phylogeny of the SARS-CoV-2 viral genome; (ii) developing nanobiosensors that could be highly effective in detecting the new coronavirus; (iii) finding effective treatments for COVID-19; and (iv) working on vaccine development. In this paper, an overview of the progress made in the development of nanobiosensors for the detection of human coronaviruses (SARS-CoV, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV) is presented, along with specific techniques for modifying the surface of nanobiosensors. The newest detection methods of the influenza virus responsible for acute respiratory syndrome were compared with conventional methods, highlighting the newest trends in diagnostics, applications, and challenges of SARS-CoV-2 (COVID-19 causative virus) nanobiosensors.

Sensors (Basel)2020       LitCov and CORD-19
1397Mathematical modeling of COVID-19 transmission: the roles of intervention strategies and lockdown  

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Math Biosci Eng2020       LitCov and CORD-19
1398Cell entry mechanisms of SARS-CoV-2  

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness.

Proc Natl Acad Sci U S A2020       LitCov and CORD-19
1399Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20-28 January 2020  

A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.

Euro Surveill2020       LitCov and CORD-19
1400Covid-19: automatic detection from X-ray images utilizing transfer learning with convolutional neural networks  

In this study, a dataset of X-ray images from patients with common bacterial pneumonia, confirmed Covid-19 disease, and normal incidents, was utilized for the automatic detection of the Coronavirus disease. The aim of the study is to evaluate the performance of state-of-the-art convolutional neural network architectures proposed over the recent years for medical image classification. Specifically, the procedure called Transfer Learning was adopted. With transfer learning, the detection of various abnormalities in small medical image datasets is an achievable target, often yielding remarkable results. The datasets utilized in this experiment are two. Firstly, a collection of 1427 X-ray images including 224 images with confirmed Covid-19 disease, 700 images with confirmed common bacterial pneumonia, and 504 images of normal conditions. Secondly, a dataset including 224 images with confirmed Covid-19 disease, 714 images with confirmed bacterial and viral pneumonia, and 504 images of normal conditions. The data was collected from the available X-ray images on public medical repositories. The results suggest that Deep Learning with X-ray imaging may extract significant biomarkers related to the Covid-19 disease, while the best accuracy, sensitivity, and specificity obtained is 96.78%, 98.66%, and 96.46% respectively. Since by now, all diagnostic tests show failure rates such as to raise concerns, the probability of incorporating X-rays into the diagnosis of the disease could be assessed by the medical community, based on the findings, while more research to evaluate the X-ray approach from different aspects may be conducted.

Phys Eng Sci Med2020       LitCov and CORD-19

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

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