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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 145,258 papers from 615,271 authors.

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1: Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag
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Posted 31 Jan 2020

Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag
1,597,053 downloads bioRxiv evolutionary biology

Prashant Pradhan, Ashutosh Kumar Pandey, Akhilesh Mishra, Parul Gupta, Praveen Kumar Tripathi, Manoj Balakrishnan Menon, James Gomes, Perumal Vivekanandan, Bishwajit Kundu

This paper has been withdrawn by its authors. They intend to revise it in response to comments received from the research community on their technical approach and their interpretation of the results. If you have any questions, please contact the corresponding author.

2: Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1
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Posted 10 Mar 2020

Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1
895,044 downloads medRxiv infectious diseases

Neeltje van Doremalen, Trenton Bushmaker, Dylan H. Morris, Myndi G Holbrook, Amandine Gamble, Brandi N. Williamson, Azaibi Tamin, Jennifer L. Harcourt, Natalie J. Thornburg, Susan I. Gerber, James O. Lloyd-Smith, Emmie de Wit, Vincent Munster

To the EditorA novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic1. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model (see Supplementary Appendix). All experimental measurements are reported as mean across 3 replicates.

3: Estimating the effective reproduction number of the 2019-nCoV in China
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Posted 29 Jan 2020

Estimating the effective reproduction number of the 2019-nCoV in China
543,528 downloads medRxiv infectious diseases

Zhidong Cao, Qingpeng Zhang, Xin Lu, Dirk Pfeiffer, Zhongwei Jia, Hongbing Song, Dajun Zeng

We estimate the effective reproduction number for 2019-nCoV based on the daily reported cases from China CDC. The results indicate that 2019-nCoV has a higher effective reproduction number than SARS with a comparable fatality rate. Article Summary LineThis modeling study indicates that 2019-nCoV has a higher effective reproduction number than SARS with a comparable fatality rate.

4: Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
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Posted 21 Apr 2020

Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
449,667 downloads medRxiv infectious diseases

Joseph Magagnoli, Siddharth Narendran, Felipe Pereira, Tammy Cummings, James W Hardin, S Scott Sutton, Jayakrishna Ambati

BACKGROUND: Despite limited and conflicting data on the use of hydroxychloroquine in patients with Covid-19, the U.S. Food and Drug Administration has authorized the emergency use of this drug when clinical trials are unavailable or infeasible. Hydroxychloroquine, alone or in combination with azithromycin, is being widely used in Covid-19 therapy based on anecdotal and limited observational evidence. METHODS: We performed a retrospective analysis of data from patients hospitalized with confirmed SARS-CoV-2 infection in all United States Veterans Health Administration medical centers until April 11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for Covid-19. The two primary outcomes were death and the need for mechanical ventilation. We determined the association between treatment and the primary outcomes using competing risk hazard regression adjusting for clinical characteristics via propensity scores. Discharge and death were taken into account as competing risks and subdistribution hazard ratios are presented. RESULTS: A total of 368 patients were evaluated (HC, n=97; HC+AZ, n=113; no HC, n=158). Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively. Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively. Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72). The risk of ventilation was similar in the HC group (adjusted hazard ratio, 1.43; 95% CI, 0.53 to 3.79; P=0.48) and in the HC+AZ group (adjusted hazard ratio, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group. CONCLUSIONS: In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.

5: Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions
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Posted 24 Jan 2020

Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions
387,135 downloads medRxiv infectious diseases

Jonathan M Read, Jessica R.E. Bridgen, Derek A. T. Cummings, Antonia Ho, Chris P. Jewell

Since first identified, the epidemic scale of the recently emerged novel coronavirus (2019-nCoV) in Wuhan, China, has increased rapidly, with cases arising across China and other countries and regions. using a transmission model, we estimate a basic reproductive number of 3.11 (95%CI, 2.39-4.13); 58-76% of transmissions must be prevented to stop increasing; Wuhan case ascertainment of 5.0% (3.6-7.4); 21022 (11090-33490) total infections in Wuhan 1 to 22 January. Changes to previous versionO_LIcase data updated to include 22 Jan 2020; we did not use cases reported after this period as cases were reported at the province level hereafter, and large-scale control interventions were initiated on 23 Jan 2020; C_LIO_LIimproved likelihood function, better accounting for first 41 confirmed cases, and now using all infections (rather than just cases detected) in Wuhan for prediction of infection in international travellers; C_LIO_LIimproved characterization of uncertainty in parameters, and calculation of epidemic trajectory confidence intervals using a more statistically rigorous method; C_LIO_LIextended range of latent period in sensitivity analysis to reflect reports of up to 6 day incubation period in household clusters; C_LIO_LIremoved travel restriction analysis, as different modelling approaches (e.g. stochastic transmission, rather than deterministic transmission) are more appropriate to such analyses. C_LI

6: Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study
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Posted 28 Mar 2020

Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study
354,202 downloads medRxiv epidemiology

Aaron Miller, Mac Josh Reandelar, Kimberly Fasciglione, Violeta Roumenova, Yan Li, Gonzalo H Otazu

COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID- 19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guerin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.

7: Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin
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Posted 23 Jan 2020

Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin
286,462 downloads bioRxiv microbiology

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang, Ben Hu, Lei Zhang, Wei Zhang, Hao-Rui Si, Yan Zhu, Bei Li, Chao-Lin Huang, Hui-Dong Chen, Jing Chen, Yun Luo, Hua Guo, Ren-Di Jiang, Mei-Qin Liu, Ying Chen, Xu-Rui Shen, Xi Wang, Xiao-Shuang Zheng, Kai Zhao, Quan-Jiao Chen, Fei Deng, Lin-Lin Liu, Bing Yan, Fa-Xian Zhan, Yan-Yi Wang, Gengfu Xiao, Zheng-Li Shi

Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.

8: Report of Partial findings from the National Toxicology Program Carcinogenesis Studies of Cell Phone Radiofrequency Radiation in Hsd: Sprague Dawley® SD rats (Whole Body Exposure)
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Posted 26 May 2016

Report of Partial findings from the National Toxicology Program Carcinogenesis Studies of Cell Phone Radiofrequency Radiation in Hsd: Sprague Dawley® SD rats (Whole Body Exposure)
277,346 downloads bioRxiv cancer biology

Michael Wyde, Mark Cesta, Chad Blystone, Susan Elmore, Paul Foster, Michelle Hooth, Grace Kissling, David Malarkey, Robert Sills, Matthew Stout, Nigel Walker, Kristine Witt, Mary Wolfe, John Bucher

The U.S. National Toxicology Program (NTP) has carried out extensive rodent toxicology and carcinogenesis studies of radiofrequency radiation (RFR) at frequencies and modulations used in the U.S. telecommunications industry. This report presents partial findings from these studies. The occurrences of two tumor types in male Harlan Sprague Dawley rats exposed to RFR, malignant gliomas in the brain and schwannomas of the heart, were considered of particular interest and are the subject of this report. The findings in this report were reviewed by expert peer reviewers selected by the NTP and National Institutes of Health (NIH). These reviews and responses to comments are included as appendices to this report, and revisions to the current document have incorporated and addressed these comments. When the studies are completed, they will undergo additional peer review before publication in full as part of the NTP's Toxicology and Carcinogenesis Technical Reports Series. No portion of this work has been submitted for publication in a scientific journal. Supplemental information in the form of four additional manuscripts has or will soon be submitted for publication. These manuscripts describe in detail the designs and performance of the RFR exposure system, the dosimetry of RFR exposures in rats and mice, the results to a series of pilot studies establishing the ability of the animals to thermoregulate during RFR exposures, and studies of DNA damage. (1) Capstick M, Kuster N, Kuhn S, Berdinas-Torres V, Wilson P, Ladbury J, Koepke G, McCormick D, Gauger J, and Melnick R. A radio frequency radiation reverberation chamber exposure system for rodents; (2) Yijian G, Capstick M, McCormick D, Gauger J, Horn T, Wilson P, Melnick RL, and Kuster N. Life time dosimetric assessment for mice and rats exposed to cell phone radiation; (3) Wyde ME, Horn TL, Capstick M, Ladbury J, Koepke G, Wilson P, Stout MD, Kuster N, Melnick R, Bucher JR, and McCormick D. Pilot studies of the National Toxicology Program's cell phone radiofrequency radiation reverberation chamber exposure system; (4) Smith-Roe SL, Wyde ME, Stout MD, Winters J, Hobbs CA, Shepard KG, Green A, Kissling GE, Tice RR, Bucher JR, and Witt KL. Evaluation of the genotoxicity of cell phone radiofrequency radiation in male and female rats and mice following subchronic exposure.

9: COVID-19 Antibody Seroprevalence in Santa Clara County, California
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Posted 17 Apr 2020

COVID-19 Antibody Seroprevalence in Santa Clara County, California
275,316 downloads medRxiv epidemiology

Eran Bendavid, Bianca Mulaney, Neeraj Sood, Soleil Shah, Emilia Ling, Rebecca Bromley-Dulfano, Cara Lai, Zoe Weissberg, Rodrigo Saavedra-Walker, James Tedrow, Dona Tversky, Andrew Bogan, Thomas Kupiec, Daniel Eichner, Ribhav Gupta, John Ioannidis, Jay Bhattacharya

Background Addressing COVID-19 is a pressing health and social concern. To date, many epidemic projections and policies addressing COVID-19 have been designed without seroprevalence data to inform epidemic parameters. We measured the seroprevalence of antibodies to SARS-CoV-2 in a community sample drawn from Santa Clara County. Methods On April 3-4, 2020, we tested county residents for antibodies to SARS-CoV-2 using a lateral flow immunoassay. Participants were recruited using Facebook ads targeting a sample of individuals living within the county by demographic and geographic characteristics. We estimate weights to adjust our sample to match the zip code, sex, and race/ethnicity distribution within the county. We report both the weighted and unweighted prevalence of antibodies to SARS-CoV-2. We also adjust for test performance characteristics by combining data from 16 independent samples obtained from manufacturer's data, regulatory submissions, and independent evaluations: 13 samples for specificity (3,324 specimens) and 3 samples for sensitivity (157 specimens). Results The raw prevalence of antibodies to SARS-CoV-2 in our sample was 1.5% (exact binomial 95CI 1.1-2.0%). Test performance specificity in our data was 99.5% (95CI 99.2-99.7%) and sensitivity was 82.8% (95CI 76.0-88.4%). The unweighted prevalence adjusted for test performance characteristics was 1.2% (95CI 0.7-1.8%). After weighting for population demographics of Santa Clara County, the prevalence was 2.8% (95CI 1.3-4.7%), using bootstrap to estimate confidence bounds. These prevalence point estimates imply that 54,000 (95CI 25,000 to 91,000 using weighted prevalence; 23,000 with 95CI 14,000-35,000 using unweighted prevalence) people were infected in Santa Clara County by early April, many more than the approximately 1,000 confirmed cases at the time of the survey. Conclusions The estimated population prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that the infection may be much more widespread than indicated by the number of confirmed cases. More studies are needed to improve precision of prevalence estimates. Locally-derived population prevalence estimates should be used to calibrate epidemic and mortality projections.

10: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2
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Posted 30 Apr 2020

Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2
248,782 downloads bioRxiv evolutionary biology

Bette Korber, WM Fischer, S. Gnanakaran, H Yoon, J Theiler, W Abfalterer, Brian T. Foley, EE Giorgi, T Bhattacharya, MD Parker, DG Partridge, CM Evans, TM Freeman, Thushan de Silva, on behalf of the Sheffield COVID-19 Genomics Group, CC LaBranche, DC Montefiori

We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; after beginning to spread in Europe in early February, when introduced to new regions it repeatedly and rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions. ### Competing Interest Statement The authors have declared no competing interest.

11: Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
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Posted 30 Mar 2020

Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
245,153 downloads medRxiv epidemiology

Zhaowei Chen, Jijia Hu, Zongwei Zhang, Shan Jiang, Shoumeng Han, Dandan Yan, Ruhong Zhuang, Ben Hu, Zhan Zhang

AimsStudies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methodsFrom February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findingsFor the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. SignificanceAmong patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia. Trial registrationURL: https://www.clinicaltrials.gov/. The unique identifier: ChiCTR2000029559.

12: The infection fatality rate of COVID-19 inferred from seroprevalence data
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Posted 19 May 2020

The infection fatality rate of COVID-19 inferred from seroprevalence data
243,993 downloads medRxiv infectious diseases

John Ioannidis

Objective To estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies. Methods Population studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of July 11, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Secondarily, results from national studies were also examined from preliminary press releases and reports whenever a country had no other data presented in full papers of preprints. Results 36 studies (43 estimates) were identified with usable data to enter into calculations and another 7 preliminary national estimates were also considered for a total of 50 estimates. Seroprevalence estimates ranged from 0.222% to 47%. Infection fatality rates ranged from 0.00% to 1.63% and corrected values ranged from 0.00% to 1.31%. Across 32 different locations, the median infection fatality rate was 0.27% (corrected 0.24%). Most studies were done in pandemic epicenters with high death tolls. Median corrected IFR was 0.10% in locations with COVID-19 population mortality rate less than the global average (<73 deaths per million as of July 12, 2020), 0.27% in locations with 73-500 COVID-19 deaths per million, and 0.90% in locations exceeding 500 COVID-19 deaths per million. Among people <70 years old, infection fatality rates ranged from 0.00% to 0.57% with median of 0.05% across the different locations (corrected median of 0.04%). Conclusions The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.

13: Transmission Potential of SARS-CoV-2 in Viral Shedding Observed at the University of Nebraska Medical Center
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Posted 26 Mar 2020

Transmission Potential of SARS-CoV-2 in Viral Shedding Observed at the University of Nebraska Medical Center
231,121 downloads medRxiv infectious diseases

Joshua L Santarpia, Danielle N Rivera, Vicki Herrera, M. Jane Morwitzer, Hannah Creager, George W. Santarpia, Kevin K Crown, David Brett-Major, Elizabeth Schnaubelt, M. Jana Broadhurst, James V. Lawler, St Patrick Reid, John J. Lowe

Lack of evidence on SARS-CoV-2 transmission dynamics has led to shifting isolation guidelines between airborne and droplet isolation precautions. During the initial isolation of 13 individuals confirmed positive with COVID-19 infection, air and surface samples were collected in eleven isolation rooms to examine viral shedding from isolated individuals. While all individuals were confirmed positive for SARS-CoV-2, symptoms and viral shedding to the environment varied considerably. Many commonly used items, toilet facilities, and air samples had evidence of viral contamination, indicating that SARS-CoV-2 is shed to the environment as expired particles, during toileting, and through contact with fomites. Disease spread through both direct (droplet and person-to-person) as well as indirect contact (contaminated objects and airborne transmission) are indicated, supporting the use of airborne isolation precautions. One Sentence SummarySARS-CoV-2 is shed during respiration, toileting, and fomite contact, indicating that infection may occur in both direct and indirect contact.

14: Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster
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Posted 08 Mar 2020

Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster
207,972 downloads medRxiv infectious diseases

Roman Wölfel, Victor M Corman, Wolfgang Guggemos, Michael Seilmaier, Sabine Zange, Marcel A Müller, Daniela Niemeyer, Terence C. Jones Kelly, Patrick Vollmar, Camilla Rothe, Michael Hoelscher, Tobias Bleicker, Sebastian Brünink, Julia Schneider, Rosina Ehmann, Katrin Zwirglmaier, Christian Drosten, Clemens Wendtner

Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 20191,2. Initial outbreaks in China involved 13.8% cases with severe-, and 6.1% with critical courses3. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung2,4. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity but also aided the control of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting a potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on body site - specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 x 108 RNA copies per throat swab, day 4). Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat- and lung samples of one same patient. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 6-12 days, but was not followed by a rapid decline of viral loads. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts prospects of COVID-19 containment in perspective.

15: Clinical characteristics of 2019 novel coronavirus infection in China
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Posted 09 Feb 2020

Clinical characteristics of 2019 novel coronavirus infection in China
204,363 downloads medRxiv respiratory medicine

Wei-jie Guan, Zheng-yi Ni, Yu Hu, Wen-hua Liang, Chun-quan Ou, Jian-xing He, Lei Liu, Hong Shan, Chun-liang Lei, David S.C. Hui, Bin Du, Lan-juan Li, Guang Zeng, Kwok-Yung Yuen, Ru-chong Chen, Chun-li Tang, Tao Wang, Ping-yan Chen, Jie Xiang, Shi-yue Li, Jin-lin Wang, Zi-jing Liang, Yi-xiang Peng, Li Wei, Yong Liu, Ya-hua Hu, Peng Peng, Jian-ming Wang, Ji-yang Liu, Zhong Chen, Gang Li, Zhi-jian Zheng, Shao-qin Qiu, Jie Luo, Chang-jiang Ye, Shao-yong Zhu, Nan-shan Zhong, on behalf of China Medical Treatment Expert Group for 2019-nCoV

BackgroundSince December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. MethodsWe extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29th, 2020. ResultsThe median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P<0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). ConclusionsThe 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.

16: Indoor transmission of SARS-CoV-2
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Posted 07 Apr 2020

Indoor transmission of SARS-CoV-2
198,358 downloads medRxiv infectious diseases

Hua Qian, Te Miao, Li Liu, Xiaohong Zheng, Danting Luo, Yuguo Li

BackgroundBy early April 2020, the COVID-19 pandemic had infected nearly one million people and had spread to nearly all countries worldwide. It is essential to understand where and how SARS-CoV-2 is transmitted. MethodsCase reports were extracted from the local Municipal Health Commissions of 320 prefectural cities (municipalities) in China, not including Hubei province, between 4 January and 11 February 2020. We identified all outbreaks involving three or more cases and reviewed the major characteristics of the enclosed spaces in which the outbreaks were reported and associated indoor environmental issues. ResultsThree hundred and eighteen outbreaks with three or more cases were identified, involving 1245 confirmed cases in 120 prefectural cities. We divided the venues in which the outbreaks occurred into six categories: homes, transport, food, entertainment, shopping, and miscellaneous. Among the identified outbreaks, 53{middle dot}8% involved three cases, 26{middle dot}4% involved four cases, and only 1{middle dot}6% involved ten or more cases. Home outbreaks were the dominant category (254 of 318 outbreaks; 79{middle dot}9%), followed by transport (108; 34{middle dot}0%; note that many outbreaks involved more than one venue category). Most home outbreaks involved three to five cases. We identified only a single outbreak in an outdoor environment, which involved two cases. ConclusionsAll identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk. FundingThe work was supported by the Research Grants Council of Hong (no 17202719, C7025-16G), and National Natural Science Foundation of China (no 41977370).

17: An integrated brain-machine interface platform with thousands of channels
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Posted 17 Jul 2019

An integrated brain-machine interface platform with thousands of channels
196,232 downloads bioRxiv neuroscience

Elon Musk, Neuralink

Brain-machine interfaces (BMIs) hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical BMIs have not yet been widely adopted, in part because modest channel counts have limited their potential. In this white paper, we describe Neuralink’s first steps toward a scalable high-bandwidth BMI system. We have built arrays of small and flexible electrode “threads”, with as many as 3,072 electrodes per array distributed across 96 threads. We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute. Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization: the package for 3,072 channels occupies less than (23 × 18.5 × 2) mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously. This system has achieved a spiking yield of up to 70% in chronically implanted electrodes. Neuralink’s approach to BMI has unprecedented packaging density and scalability in a clinically relevant package.

18: Relationship between the ABO Blood Group and the COVID-19 Susceptibility
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Posted 16 Mar 2020

Relationship between the ABO Blood Group and the COVID-19 Susceptibility
194,487 downloads medRxiv epidemiology

Jiao Zhao, Yan Yang, Hanping Huang, Dong Li, Dongfeng Gu, Xiangfeng Lu, Zheng Zhang, Lei Liu, Ting Liu, Yukun Liu, Yunjiao He, Bin Sun, Meilan Wei, Guangyu Yang, Xinghuan Wang, Li Zhang, Xiaoyang Zhou, Mingzhao Xing, Peng George Wang

The novel coronavirus disease-2019 (COVID-19) has been spreading around the world rapidly and declared as a pandemic by WHO. Here, we compared the ABO blood group distribution in 2,173 patients with COVID-19 confirmed by SARS-CoV-2 test from three hospitals in Wuhan and Shenzhen, China with that in normal people from the corresponding regions. The results showed that blood group A was associated with a higher risk for acquiring COVID-19 compared with non-A blood groups, whereas blood group O was associated with a lower risk for the infection compared with non-O blood groups. This is the first observation of an association between the ABO blood type and COVID-19. It should be emphasized, however, that this is an early study with limitations. It would be premature to use this study to guide clinical practice at this time, but it should encourage further investigation of the relationship between the ABO blood group and the COVID-19 susceptibility.

19: Barriers to online learning in the time of COVID-19: A national survey of medical students in the Philippines
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Posted 18 Jul 2020

Barriers to online learning in the time of COVID-19: A national survey of medical students in the Philippines
189,288 downloads medRxiv medical education

Ronnie E Baticulon, Nicole Rose I Alberto, Maria Beatriz C Baron, Robert Earl C Mabulay, Lloyd Gabriel T Rizada, Jinno Jenkin Sy, Christl Jan S Tiu, Charlie A Clarion, John Carlo B Reyes

INTRODUCTION: In March 2020, the coronavirus disease 2019 (COVID-19) pandemic forced medical schools in the Philippines to stop face-to-face learning activities and abruptly shift to an online curriculum. This study aimed to identify barriers to online learning from the perspective of medical students in a developing country. METHOD: The authors sent out an electronic survey to medical students in the Philippines from 11 to 24 May 2020. Using a combination of multiple choice, Likert scale, and open-ended questions, the following data were obtained: demographics, medical school information, access to technological resources, study habits, living conditions, self-assessment of capacity for and perceived barriers to online learning, and proposed interventions. Descriptive statistics were calculated. Responses were compared between student subgroups using nonparametric tests. RESULTS: Among 3,670 medical students, 3,421 (93%) owned a smartphone and 3,043 (83%) had a laptop or desktop computer. To access online resources, 2,916 (79%) had a postpaid internet subscription while 696 (19%) used prepaid mobile data. Under prevailing conditions, only 1,505 students (41%) considered themselves physically and mentally capable of engaging in online learning. Barriers were classified under five categories: technological, individual, domestic, institutional, and community barriers. Most frequently encountered were difficulty adjusting learning styles, having to perform responsibilities at home, and poor communication between educators and learners. CONCLUSION: Medical students in the Philippines confronted several interrelated barriers as they tried to adapt to online learning. By implementing student-centered interventions, medical schools and educators play a significant role in addressing these challenges during the COVID-19 pandemic and beyond.

20: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
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Posted 22 Mar 2020

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
175,839 downloads bioRxiv systems biology

David E Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O'Meara, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J. McGregor, Qiongyu Li, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ilsa T Kirby, James E Melnyk, John S Chorba, Kevin Lou, Shizhong A. Dai, Wenqi Shen, Ying Shi, Ziyang Zhang, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Christopher J. P. Mathy, Tina Perica, Kala Bharath Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Rakesh Ramachandran, Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Jose Liboy-Lugo, Yizhu Lin, Stephanie A Wankowicz, Markus Bohn, Phillip P. Sharp, Raphael Trenker, Janet M. Young, Devin A. Cavero, Joseph Hiatt, Theodore Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Ferdinand Roesch, Thomas Vallet, Björn Meyer, Kris M White, Lisa Miorin, Oren S. Rosenberg, Kliment A Verba, David A. Agard, Melanie Ott, Michael Emerman, Davide Ruggero, Adolfo Garcia-Sastre, Natalia Jura, Mark von Zastrow, Jack Taunton, Alan Ashworth, Olivier Schwartz, Marco Vignuzzi, Christophe d’Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik, Danica Galonic Fujimori, Trey Ideker, Charles S. Craik, Stephen N. Floor, James S. Fraser, John D. Gross, Andrej Sali, Tanja Kortemme, Pedro Beltrao, Kevan Shokat, Brian K. Shoichet, Nevan J. Krogan

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption[1][1],[2][2]. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains. * HC-PPIs : High confidence protein-protein interactions PPIs : protein-protein interaction AP-MS : affinity purification-mass spectrometry COVID-19 : Coronavirus Disease-2019 ACE2 : angiotensin converting enzyme 2 Orf : open reading frame Nsp3 : papain-like protease Nsp5 : main protease Nsp : nonstructural protein TPM : transcripts per million [1]: #ref-1 [2]: #ref-2

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