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1: COVID-19 in India: State-wise Analysis and Prediction
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Posted 29 Apr 2020

COVID-19 in India: State-wise Analysis and Prediction
140,698 downloads medRxiv public and global health

Palash Ghosh, Rik Ghosh, Bibhas Chakraborty

Coronavirus disease 2019 (COVID-19), a highly infectious disease, was first detected in Wuhan, China, in December 2019. The disease has spread to 212 countries and territories around the world and infected (confirmed) more than three million people. In India, the disease was first detected on 30 January 2020 in Kerala in a student who returned from Wuhan. The total (cumulative) number of confirmed infected people is more than 37000 till now across India (3 May 2020). Most of the research and newspaper articles focus on the number of infected people in the entire country. However, given the size and diversity of India, it may be a good idea to look at the spread of the disease in each state separately, along with the entire country. For example, currently, Maharashtra has more than 10000 confirmed cumulative infected cases, whereas West Bengal has less than 800 confirmed infected cases (1 May 2020). The approaches to address the pandemic in the two states must be different due to limited resources. In this article, we will focus the infected people in each state (restricting to only those states with enough data for prediction) and build three growth models to predict infected people for that state in the next 30 days. The impact of preventive measures on daily infected-rate is discussed for each state.

2: First 12 patients with coronavirus disease 2019 (COVID-19) in the United States
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Posted 12 Mar 2020

First 12 patients with coronavirus disease 2019 (COVID-19) in the United States
105,514 downloads medRxiv public and global health

The COVID-19 Investigation Team, Stephanie A. Kujawski, Karen K Wong, Jennifer P. Collins, Lauren Epstein, Marie E. Killerby, Claire M. Midgley, Glen R. Abedi, N. Seema Ahmed, Olivia Almendares, Francisco N. Alvarez, Kayla N. Anderson, Sharon Balter, Vaughn Barry, Karri Bartlett, Karlyn Beer, Michael A. Ben-Aderet, Isaac Benowitz, Holly Biggs, Alison M. Binder, Stephanie R. Black, Brandon Bonin, Catherine M. Brown, Hollianne Bruce, Jonathan Bryant-Genevier, Alicia Budd, Diane Buell, Rachel Bystritsky, Jordan Cates, E. Matt Charles, Kevin Chatham-Stephens, Nora Chea, Howard Chiou, Demian Christiansen, Victoria Chu, Sara Cody, Max Cohen, Erin Conners, Aaron Curns, Vishal Dasari, Patrick Dawson, Traci DeSalvo, George Diaz, Matthew Donahue, Suzanne Donovan, Lindsey M. Duca, Keith Erickson, Mathew D. Esona, Suzanne Evans, Jeremy Falk, Leora R. Feldstein, Martin Fenstersheib, Marc Fischer, Rebecca Fisher, Chelsea Foo, Marielle J. Fricchione, Oren Friedman, Alicia M. Fry, Romeo R. Galang, Melissa M. Garcia, Susa I. Gerber, Graham Gerrard, Isaac Ghinai, Prabhu Gounder, Jonathan Grein, Cheri Grigg, Jeffrey D. Gunzenhauser, Gary I. Gutkin, Meredith Haddix, Aron J Hall, George Han, Jennifer Harcourt, Kathleen Harriman, Thomas Haupt, Amber Haynes, Michelle Holshue, Cora Hoover, Jennifer C. Hunter, Max W. Jacobs, Claire Jarashow, Michael A. Jhung, Kiran Joshi, Talar Kamali, Shifaq Kamili, Lindsay Kim, Moon Kim, Jan King, Hannah L. Kirking, Amanda Kita-Yarbro, Rachel Klos, Miwako Kobayashi, Anna Kocharian, Kenneth K. Komatsu, Ram Koppaka, Jennifer E. Layden, Yan Li, Scott Lindquist, Stephen Lindstrom, Ruth Link-Gelles, Joana Lively, Michelle Livingston, Kelly Lo, Jennifer Lo, Xiaoyan Lu, Brian Lynch, Larry Madoff, Lakshmi Malapati, Gregory Marks, Mariel Marlow, Glenn E. Mathisen, Nancy McClung, Olivia McGovern, Tristan D. McPherson, Mitali Mehta, Audrey Meier, Lynn Mello, Sung-sil Moon, Margie Morgan, Ruth N. Moro, Janna' Murray, Rekha Murthy, Shannon Novosad, Sara E. Oliver, Jennifer O'Shea, Massimo Pacilli, Clinton R Paden, Mark A. Pallansch, Manisha Patel, Sajan Patel, Isabel Pedraza, Satish K Pillai, Talia Pindyck, Ian Pray, Krista Queen, Nichole Quick, Heather Reese, Brian Rha, Heather Rhodes, Susan Robinson, Philip Robinson, Melissa Rolfes, Janell Routh, Rachel Rubin, Sarah L. Rudman, Senthilkumar K. Sakthivel, Sarah Scott, Christopher Shepherd, Varun Shetty, Ethan A. Smith, Shanon Smith, Bryan Stierman, William Stoecker, Rebecca Sunenshine, Regina Sy-Santos, Azaibi Tamin, Ying Tao, Dawn Terashita, Natalie J. Thornburg, Suxiang Tong, Elizabeth Traub, Ahmet Tural, Anna Uehara, Timothy M. Uyeki, Grace Vahey, Jennifer R. Verani, Elsa Villarino, Megan Wallace, Lijuan Wang, John T. Watson, Matthew Westercamp, Brett Whitaker, Sarah Wilkerson, Rebecca C. Woodruff, Jonathan M. Wortham, Tiffany Wu, Amy Xie, Anna Yousaf, Matthew Zahn, Jing Zhang

IntroductionMore than 93,000 cases of coronavirus disease (COVID-19) have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. MethodsWe collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. ResultsAmong the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. ConclusionsIn 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset.

3: Adherence to the test, trace and isolate system: results from a time series of 21 nationally representative surveys in the UK (the COVID-19 Rapid Survey of Adherence to Interventions and Responses study)
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Posted 18 Sep 2020

Adherence to the test, trace and isolate system: results from a time series of 21 nationally representative surveys in the UK (the COVID-19 Rapid Survey of Adherence to Interventions and Responses study)
41,130 downloads medRxiv public and global health

Louise E. Smith, Henry W W Potts, Richard Amlot, Nicola T. Fear, Susan Michie, G James Rubin

Objectives: To investigate rates of adherence to the UKs test, trace and isolate system over time. Design: Time series of cross-sectional online surveys. Setting: Data were collected between 2 March and 5 August 2020. Participants: 42,127 responses from 31,787 people living in the UK, aged 16 years or over, are presented (21 survey waves, n{approx}2,000 per wave). Main outcome measures: Identification of the key symptoms of COVID-19 (cough, high temperature / fever, and loss of sense of smell or taste), self-reported adherence to self-isolation if symptomatic, requesting an antigen test if symptomatic, intention to share details of close contacts, self-reported adherence to quarantine if alerted that you had been in contact with a confirmed COVID-19 case. Results: Only 48.9% of participants (95% CI 48.2% to 49.7%) identified key symptoms of COVID-19. Self-reported adherence to test, trace and isolate behaviours was low (self-isolation 18.2%, 95% CI 16.4% to 19.9%; requesting an antigen test 11.9%, 95% CI 10.1% to 13.8%; intention to share details of close contacts 76.1%, 95% CI 75.4% to 76.8%; quarantining 10.9%, 95% CI 7.8% to 13.9%) and largely stable over time. By contrast, intention to adhere to protective measures was much higher. Non-adherence was associated with: men, younger age groups, having a dependent child in the household, lower socio-economic grade, greater hardship during the pandemic, and working in a key sector. Conclusions: Practical support and financial reimbursement is likely to improve adherence. Targeting messaging and policies to men, younger age groups, and key workers may also be necessary.

4: Covid-19 Risk Among Airline Passengers: Should the Middle Seat Stay Empty?
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Posted 05 Jul 2020

Covid-19 Risk Among Airline Passengers: Should the Middle Seat Stay Empty?
40,932 downloads medRxiv public and global health

Arnold Barnett, Keith Fleming

We use recent data and research results and a probabilistic model to estimate the chance that an air traveler in coach will contract Covid-19 on a US domestic jet flight two hours long, both when all coach seats are full and when all but middle seats are full. The point estimates we reach based on data from late September 2020 are about 1 in 3,900 for full flights and 1 in 6,400 when middle seats are kept empty. These estimates are subject to substantial uncertainty, with factor-of-three or greater margins of error. However, because uncertainties in key parameters affect both risk estimates the same way, they leave the relative risk ratio for "fill all seats" compared to "middle seat open" close to 1.64 (i.e., close to (1/3,900)/(1/6,400). We compare the infection risks over a two-hour flight to those of two hours on the ground, and find that the flight presents greater hazard. We also approximate the mortality risks caused by Covid-19 infections contracted on airplanes, taking into account that infected passengers can in turn infect others not on the plane. The point estimates for death risk are low--averaging about one death per 800,000 passengers--but they are somewhat higher than those associated with plane crashes and aviation terrorism.

5: ICON (Ivermectin in COvid Nineteen) study: Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19
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Posted 09 Jun 2020

ICON (Ivermectin in COvid Nineteen) study: Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID19
37,911 downloads medRxiv public and global health

Juliana Cepelowicz Rajter, Michael Sherman, Naaz Fatteh, Fabio Vogel, Jamie Sacks, Jean-Jacques Rajter

Abstract Importance: No therapy to date has been shown to improve survival for patients infected with SARS-CoV-2. Ivermectin has been shown to inhibit the replication of SARS-CoV-2 in vitro but clinical response has not been previously evaluated. Objective: To determine whether Ivermectin is associated with lower mortality rate in patients hospitalized with COVID-19. Design and Setting: Retrospective cohort study of consecutive patients hospitalized at four Broward Health hospitals in South Florida with confirmed SARS-CoV-2. Enrollment dates were March 15, 2020 through May 11, 2020. Follow up data for all outcomes was May 19, 2020. Participants: 280 patients with confirmed SARS-CoV-2 infection (mean age 59.6 years [standard deviation 17.9], 45.4% female), of whom 173 were treated with ivermectin and 107 were usual care were reviewed. 27 identified patients were not reviewed due to multiple admissions, lack of confirmed COVID results during hospitalization, age less than 18, pregnancy, or incarceration. Exposure: Patients were categorized into two treatment groups based on whether they received at least one dose of ivermectin at any time during the hospitalization. Treatment decisions were at the discretion of the treating physicians. Severe pulmonary involvement at study entry was characterized as need for either FiO2 [≥]50%, or noninvasive or invasive mechanical ventilation. Main Outcomes and Measures: The primary outcome was all-cause in-hospital mortality. Secondary outcomes included subgroup mortality in patients with severe pulmonary involvement and extubation rates for patients requiring invasive ventilation. Results: Univariate analysis showed lower mortality in the ivermectin group (25.2% versus 15.0%, OR 0.52, 95% CI 0.29-0.96, P=.03). Mortality was also lower among 75 patients with severe pulmonary disease treated with ivermectin (38.8% vs 80.7%, OR 0.15, CI 0.05-0.47, P=.001), but there was no significant difference in successful extubation rates (36.1% vs 15.4%, OR 3.11 (0.88-11.00), p=.07). After adjustment for between-group differences and mortality risks, the mortality difference remained significant for the entire cohort (OR 0.27, CI 0.09-0.85, p=.03; HR 0.37, CI 0.19-0.71, p=.03). Conclusions and Relevance: Ivermectin was associated with lower mortality during treatment of COVID-19, especially in patients who required higher inspired oxygen or ventilatory support. These findings should be further evaluated with randomized controlled trials.

6: Validity of Wrist and Forehead Temperature in Temperature Screening in the General Population During the Outbreak of 2019 Novel Coronavirus: a prospective real-world study
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Posted 06 Mar 2020

Validity of Wrist and Forehead Temperature in Temperature Screening in the General Population During the Outbreak of 2019 Novel Coronavirus: a prospective real-world study
33,658 downloads medRxiv public and global health

Ge Chen, Jiarong Xie, Guangli Dai, Peijun Zheng, Xiaqing Hu, Hongpeng Lu, Lei Xu, Xueqin Chen, Xiaomin Chen

AimsTemperature screening is important in the population during the outbreak of 2019 Novel Coronavirus (COVID-19). This study aimed to compare the accuracy and precision of wrist and forehead temperature with tympanic temperature under different circumstances. MethodsWe performed a prospective observational study in a real-life population. We consecutively collected wrist and forehead temperatures in Celsius ({degrees}C) using a non-contact infrared thermometer (NCIT). We also measured the tympanic temperature using a tympanic thermometers (IRTT) and defined fever as a tympanic temperature [&ge;]37.3{degrees}C. ResultsWe enrolled a total of 528 participants including 261 indoor and 267 outdoor participants. We divided outdoor participants into four types according to their means of transportation to the hospital as walk, bicycle, electric vehicle, car, and inside the car. Under different circumstance, the mean difference ranged from -1.72 to -0.56{degrees}C in different groups for the forehead measurements, and -0.96 to -0.61{degrees}C for the wrist measurements. Both measurements had high fever screening abilities in inpatients (wrist: AUC 0.790; 95% CI: 0.725-0.854, P <0.001; forehead: AUC 0.816; 95% CI: 0.757-0.876, P <0.001). The cut-off value of wrist measurement for detecting tympanic temperature [&ge;]37.3{degrees}C was 36.2{degrees}C with a 86.4% sensitivity and a 67.0% specificity, and the best threshold of forehead measurement was also 36.2{degrees}C with a 93.2% sensitivity and a 60.0% specificity. ConclusionsWrist measurement is more stable than forehead measurement under different circumstance. Both measurements have great fever screening abilities for indoor patients. The cut-off value of both measurements was 36.2{degrees}C. (ClinicalTrials.gov number: NCT04274621)

7: Randomized Re-Opening of Training Facilities during the COVID-19 pandemic
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Posted 24 Jun 2020

Randomized Re-Opening of Training Facilities during the COVID-19 pandemic
32,998 downloads medRxiv public and global health

Lise M. Helsingen, Magnus Løberg, Erle Refsum, Dagrun Kyte Gjøstein, Paulina Wieszczy, Ørjan Olsvik, Frederik E. Juul, Ishita Barua, Henriette C. Jodal, Magnhild Herfindal, Yuichi Mori, Solveig Jore, Fridtjof Lund-Johansen, Atle Fretheim, Michael Bretthauer, Mette Kalager, for the TRAiN study group

BackgroundClosed training facilities during the Covid-19 pandemic may negatively impact peoples health and wellbeing. We investigated SARS-CoV-2 virus transmission, Covid-19 and SARS-CoV-2 antibodies attributable to training facilities. MethodsWe randomised members aged 18 to 64 without relevant comorbidities at five training facilities in Oslo, Norway, to access or no access to their facility. Facilities opened May 22, 2020 for the training arm, applying physical distancing (1 meter for floor exercise, 2 meters for high-intensity classes) and enhanced hand and surface hygiene. We compared SARS-CoV-2 RNA status by self-administered naso-, oropharyngeal and sputum sampling after 14 days; clinical disease through electronic patient records after 21 days; and SARS-CoV-2 antibody status by dried-blood self-sampling after one month. (ClinicalTrials.gov number NCT04406909) Findings3,764 individuals were randomised; 1,896 in the training and 1,868 in the no-training arm. In the training arm, 81.8% trained at least once, and 38.5% trained [&ge;]six times. Of 3,016 individuals who returned the SARS-CoV-2 RNA tests (80.5%), there was one positive test. The positive individual was randomised to training, but had not used the training facility, and the workplace was identified as transmission source. There were no outpatient visits or hospital admissions due to Covid-19 in either group. Eleven individuals in the training arm (0.8% of tested) and 27 in the no-training arm (2.4% of tested) tested positive for SARS-CoV-2 antibodies (p=0.001). InterpretationProvided good hygiene and physical distancing measures, there was no increased transmission of SARS-CoV-2 at training facilities. FundingNorwegian Research Council, grant no. 312757

8: Rapid Scoping Review of Evidence of Outdoor Transmission of COVID-19
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Posted 10 Sep 2020

Rapid Scoping Review of Evidence of Outdoor Transmission of COVID-19
31,657 downloads medRxiv public and global health

Mike Weed, Abby Foad

The COVID-19 pandemic is both a global health crisis, and a civic emergency for national governments, including the UK. As countries across the world loosen their lockdown restrictions, the assumption is generally made that the risk of COVID-19 transmission is lower outdoors, and this assumption has shaped decisions about what activities can re-commence, the circumstances in which they should re-commence, and the conditions under which they should re-commence. This is important for events and activities that generate outdoor gatherings of people, including both participatory and spectator sport events, protests, concerts, carnivals, festivals, and other celebrations. The review, which was designed to be undertaken rapidly in 15 days, returned 14 sources of evidence of outdoor transmission of COVID-19, and a further 21 sources that were used to set the context and understand the caveats that should be considered in interpreting the review findings. The review found very few examples of outdoor transmission of COVID-19 in everyday life among c. 25,000 cases considered, suggesting a very low risk. However risk of outdoor transmission increases when the natural social distancing of everyday life is breached, and gathering density, circulation and size increases, particularly for an extended duration. There was also evidence that weather had a behavioural effect on transmission, with temperatures that encourage outdoor activity associated with lower COVID-19 transmission. Due to lack of surveillance and tracing systems, and confounding factors and variables, there was no evidence that robustly tested transmission at outdoor mass gatherings (circa 10,000+ people), which are as likely to generate transmission from the activities they prompt (e.g. communal travel and congregation in bars) as from outdoor transmission at the gathering itself. The goal of hosts and organisers of events and activities that generate outdoor gatherings of people is to prevent the escalation of risk from sporadic transmission to the risk of transmission through a cluster outbreak. Considerations for such hosts and organisers include: (1) does the gathering prompt other behaviours that might increase transmission risk?; (2) for each part of the event or activity, how dense is the gathering, how much do people circulate, how large is the gathering, and how long are people there?; (3) is rapid contact tracing possible in the event of an outbreak? These considerations should take place relevant to the size of the underlying risk, which includes the rate of infection in the community and the likely attendance of vulnerable groups. Risk must be balanced and mitigated across the risk factors of density, circulation, size and duration. No one risk factor presents an inherently larger risk than any other, but neither is any one risk factor a magic bullet to eliminate risk. Finally, it is clear that the largest risks from gatherings come from spontaneous or informal unregulated and unmitigated events or activities which do not consider any of the issues, risks and risk factors outlined in this paper

9: Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 1 - Face masks, eye protection and person distancing: systematic review and meta-analysis
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Posted 30 Mar 2020

Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 1 - Face masks, eye protection and person distancing: systematic review and meta-analysis
29,670 downloads medRxiv public and global health

Tom Jefferson, MA Jones, L Al-Ansary, GA Bawazeer, EM Beller, J Clark, JM Conly, C Del Mar, E Dooley, E Ferroni, P Glasziou, T Hoffmann, S Thorning, ML van Driel

OBJECTIVETo examine the effectiveness of eye protection, face masks, or person distancing on interrupting or reducing the spread of respiratory viruses. DESIGNUpdate of a Cochrane review that included a meta-analysis of observational studies during the SARS outbreak of 2003. DATA SOURCESEligible trials from the previous review; search of Cochrane Central Register of Controlled Trials, PubMed, Embase and CINAHL from October 2010 up to 1 April 2020; and forwardand backward citation analysis. DATA SELECTIONRandomised and cluster-randomised trials of people of any age, testing the use ofeye protection, face masks, or person distancing against standard practice, or a similar physical barrier. Outcomes included any acute respiratory illness and its related consequences. DATA EXTRACTION AND ANALYSISSix authors independently assessed risk of bias using the Cochrane tool and extracted data. We used a generalised inverse variance method for pooling using a random-effects model and reported results with risk ratios and 95% Confidence Intervals (CI). RESULTSWe included 15 randomised trials investigating the effect of masks (14 trials) in healthcare workers and the general population and of quarantine (1 trial). We found no trials testing eye protection. Compared to no masks there was no reduction of influenza-like illness (ILI) cases (Risk Ratio 0.93, 95%CI 0.83 to 1.05) or influenza (Risk Ratio 0.84, 95%CI 0.61-1.17) for masks in the general population, nor in healthcare workers (Risk Ratio 0.37, 95%CI 0.05 to 2.50). There was no difference between surgical masks and N95 respirators: for ILI (Risk Ratio 0.83, 95%CI 0.63 to 1.08), for influenza (Risk Ratio 1.02, 95%CI 0.73 to 1.43). Harms were poorly reported and limited to discomfort with lower compliance. The only trial testing quarantining workers with household ILI contacts found a reduction in ILI cases, but increased risk of quarantined workers contracting influenza. All trials were conducted during seasonal ILI activity. CONCLUSIONSMost included trials had poor design, reporting and sparse events. There was insufficient evidence to provide a recommendation on the use of facial barriers without other measures. We found insufficient evidence for a difference between surgical masks and N95 respirators and limited evidence to support effectiveness of quarantine. Based on observational evidence from the previous SARS epidemic included in the previous version of our Cochrane review we recommend the use of masks combined with other measures.

10: Rapid evidence summary on SARS-CoV-2 survivorship and disinfection, and a reusable PPE protocol using a double-hit process
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Posted 06 Apr 2020

Rapid evidence summary on SARS-CoV-2 survivorship and disinfection, and a reusable PPE protocol using a double-hit process
26,761 downloads medRxiv public and global health

José G B Derraik, William A Anderson, Elisabeth A Connelly, Yvonne C Anderson

In the COVID-19 pandemic caused by SARS-CoV-2, hospitals are stretched beyond capacity. There are widespread reports of dwindling supplies of personal protective equipment (PPE), which are paramount to protect frontline medical/nursing staff and to minimize further spread of the virus. We carried out a rapid review to summarize the existing evidence on SARS-CoV-2 survivorship and methods to disinfect PPE gear, particularly N95 filtering facepiece respirators (FFR). In the absence of data on SARS-CoV-2, we focused on the sister virus SARS-CoV-1. We propose a two-step disinfection process, which is conservative in the absence of robust evidence on SARS-CoV-2. This disinfection protocol is based on an initial storage of PPE for [&ge;]4 days, followed by ultraviolet light (UVC), dry heat treatment, or chemical disinfection. Importantly, each of the two steps is based on independent disinfection mechanisms, so that our proposed protocol is a multiplicative system, maximising the efficacy of our disinfection process. This method could be rapidly implemented in other healthcare settings, while testing of each method is undertaken, increasing the frontline supply of PPE, and avoiding many of the upstream issues of supply chain disruption currently being faced.

11: Estimated Average Probabilities of COVID-19 Infection, Hospitalization, and Death From Community Contact in the United States
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Posted 12 Jun 2020

Estimated Average Probabilities of COVID-19 Infection, Hospitalization, and Death From Community Contact in the United States
25,876 downloads medRxiv public and global health

Rajiv Bhatia, Jeffrey Klausner

We describe a method to estimate individual risks of hospitalization and death attributable to non-household and household transmission of SARS-CoV-2 using available public data on confirmed-case incidence data along with estimates of the clinical fraction, timing of transmission, isolation adherence, secondary infection risks, contact rates, and case-hospitalization and case-fatality ratios. Using the method, we estimate that risks for a 90-day period at the median daily summertime U.S. county confirmed COVID-19 case incidence of 10.8 per 100,000 and pre-pandemic contact rates range from 0.4 to 8.9 per 100,000 for the four deciles of age between 20 and 60 years. The corresponding 90-day period risk of hospitalization ranges from 13.7 to 69.2 per 100,000. Assuming a non-household secondary infection risk of 4% and pre-pandemic contact rates, the share of transmissions attributable to household settings ranges from 73% to 78%. These estimates are sensitive to the parameter assumptions; nevertheless, they are reasonably comparable to the COVID-19 hospitalization and fatality rates observed over the time period. We conclude that individual risk of hospitalization and death from SARS-CoV-2 infection is calculable from publicly available data sources. Access to publicly reported infection incidence data by setting and other exposure characteristics along with setting specific estimates of secondary infection risk would allow for more precise individual risk estimation.

12: A Comprehensive Analysis of COVID-19 Outbreak situation in India
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Posted 11 Apr 2020

A Comprehensive Analysis of COVID-19 Outbreak situation in India
24,474 downloads medRxiv public and global health

Rajan Gupta, Saibal Kumar Pal, Gaurav Pandey

The outbreak of COVID-19 in different parts of the world is a major concern for all the administrative units of respective countries. India is also facing this very tough task for controlling the virus outbreak and has managed its growth rate through some strict measures. This study presents the current situation of coronavirus spread in India along with the impact of various measures taken for it. With the help of data sources (till 7th-8th April 2020) from various state units of India and Ministry of Health and Family Welfare, Government of India, this study presents various trends and patterns. This study answers six different research ques-tions in a comprehensive manner. It has been reported that growth rate of infected cases has been controlled with the help of National Lockdown, however some uncontrolled mass level events had negatively impacted the infected cases. With the help of exponential and polyno-mial regression modelling, the predictions of up to 75000 cases have been done by the end of April 2020. It has also been seen that there are some prominent clusters and patient nodes in the network of patients which are the major influencers for COVID-19 spread. Also, death rate case predictions have been done through multi-class classification models with an accuracy of 75%. At the end, strategies for continuation for lockdown has been discussed and presented. It appears that only essential services should be open for the citizens of India and the national lockdown should be carried on for next 2-4 weeks. This study will be useful for the Government of India and various states of India, Administrative Units of India, Frontline health workforce of India, researchers and scientists. This study will also be favorable for the administrative units of other countries to consider various aspects related to the control of COVID-19 outspread in their respective regions.

13: Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial
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Posted 10 Aug 2020

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial
21,819 downloads medRxiv public and global health

Yan-Jun Zhang, Gang Zeng, Hong-Xing Pan, Chang-Gui Li, Biao Kan, Ya-Ling Hu, Hai-Yan Mao, Qian-Qian Xin, Kai Chu, Wei-Xiao Han, Zhen Chen, Rong Tang, Wei-Dong Yin, Xin Chen, Xue-Jie Gong, Chuan Qin, Yuan-Sheng Hu, Xiao-Yong Liu, Guo-Liang Cui, Cong-Bing Jiang, Heng-Ming Zhang, Jing-Xin Li, Min-Nan Yang, Xiao-Juan Lian, Yan Song, Jin-Xing Lu, Xiang-Xi Wang, Miao Xu, Qiang Gao, Feng-Cai Zhu

BACKGROUND The top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac). METHODS We conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 g/0.5 mL or 6 g /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay. RESULTS CoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 g dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules. CONCLUSIONS Favorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.

14: COVID-19 death rates by age and sex and the resulting mortality vulnerability of countries and regions in the world
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Posted 20 May 2020

COVID-19 death rates by age and sex and the resulting mortality vulnerability of countries and regions in the world
18,451 downloads medRxiv public and global health

Christophe Z Z Guilmoto

The growing number of series on COVID-19 deaths classified by age and sex, released by national health authorities, has allowed us to compute age and sex patterns of its mortality, based on 183,619 deaths from Western Europe and the USA. We highlight the specific age schedule of COVID-19 mortality and its pronounced excess male mortality and we then apply these COVID-19 death rates to world populations, in 2020. Our results underscore that considerable variations exist between world regions, as concerns the potential impact of COVID-19 mortality, because of their demographic structures. When compared to younger countries in Sub-Saharan Africa, the vulnerability to COVID-19 mortality is shown to be 17 times higher in several industrialized countries of East Asia and Europe. There is a high correlation (r2= .44) between demographic vulnerability to COVID-19 mortality and current COVID-19 death rates.

15: Impact of COVID-19 on the Psychological Well-Being and Turnover Intentions of Frontline Nurses in the Community: A Cross-Sectional Study in the Philippines
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Posted 06 Aug 2020

Impact of COVID-19 on the Psychological Well-Being and Turnover Intentions of Frontline Nurses in the Community: A Cross-Sectional Study in the Philippines
18,083 downloads medRxiv public and global health

Janet Alexis A. De los Santos, Leodoro J. Labrague

Purpose: This study aimed to assess fear of COVID-19 among nurses in a community setting. Methods: This study employed a cross-sectional design using self-report questionnaires. Findings: Results revealed that nurses display moderate to high fear of COVID-19 and that the female gender is correlated to fear of the virus. Moreover, the nurses fear influences their psychological distress and organizational and professional turnover intentions. Conclusion: Fear of COVID-19 is universal among nurses. There is a need to assess the factors associated with the fear to better address the nurses psychological well-being and to avoid turnover intentions.

16: Informing Homemade Emergency Facemask Design: The Ability of Common Fabrics to Filter Ultrafine Particles
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Posted 17 Apr 2020

Informing Homemade Emergency Facemask Design: The Ability of Common Fabrics to Filter Ultrafine Particles
17,521 downloads medRxiv public and global health

Eugenia O'Kelly, Sophia Pirog, James Ward, P John Clarkson

Objectives: We examined the ability of fabrics which might be used to create homemade face masks to filter out ultrafine (0.1m and smaller in diameter) particles at the velocity of adult human coughing. Method: Twenty commonly available fabrics and materials were evaluated for their ability to reduce air concentrations of ultrafine particles at a face velocity of 16.5 m/s. Further assessment was made on the filtration ability of select fabrics while damp and of fabric combinations which might be used to construct homemade masks. Results: Single fabric layers blocked a range of ultrafine particles. When fabrics were layered, significantly more ultrafine particles were filtered. Nonwoven fusible interfacing significantly increased filtration. Conclusions: The current coronavirus pandemic has left many communities without access N95 facemasks. Our findings suggest that face masks made from layered common fabric can help filter ultrafine particles and provide some protection for the wearer when commercial facemasks are unavailable.

17: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials
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Posted 18 Sep 2020

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials
15,479 downloads medRxiv public and global health

Cathrine Axfors, Andreas M. Schmitt, Perrine Janiaud, Janneke van ’t Hooft, Sherief Abd-Elsalam, Ehab F. Abdo, Benjamin S. Abella, Shehla Javed Akram, Ravi K. Amaravadi, Derek C. Angus, Yaseen M. Arabi, Shehnoor Azhar, Lindsey R. Baden, Arthur W Baker, Leila Belkhir, Thomas Benfield, Marvin A.H. Berrevoets, Cheng-Pin Chen, Tsung-Chia Chen, Shu-Hsing Cheng, Chien-Yu Cheng, Wei-Sheng Chung, Yehuda Z. Cohen, Lisa N. Cowan, Olav Dalgard, Fernando F. de Almeida e Val, Marcus V.G. de Lacerda, Gisely C. de Melo, Lennie Derde, Vincent Dubee, Anissa Elfakir, Anthony C. Gordon, Carmen M. Hernandez-Cardenas, Thomas Hills, Andy I.M. Hoepelman, Yi-Wen Huang, Bruno Igau, Ronghua Jin, Felipe Jurado-Camacho, Khalid S. Khan, Peter G. Kremsner, Benno Kreuels, Cheng-Yu Kuo, Thuy Le, Yi-Chun Lin, Wu-Pu Lin, Tse-Hung Lin, Magnus Nakrem Lyngbakken, Colin McArthur, Bryan J. McVerry, Patricia Meza-Meneses, Wuelton M Monteiro, Susan C Morpeth, Ahmad Mourad, Mark J Mulligan, Srinivas Murthy, Susanna Naggie, Shanti Narayanasamy, Alistair D Nichol, Lewis A. Novack, Sean M. O’Brien, Nwora Lance Okeke, Léna Perez, Rogelio Perez-Padilla, Laurent Perrin, Arantxa Remigio-Luna, Norma E. Rivera-Martinez, Frank W. Rockhold, Sebastian Rodriguez-Llamazares, Robert Rolfe, Rossana Rosa, Helge Røsjø, Vanderson S Sampaio, Todd B. Seto, Muhammad Shehzad, Shaimaa Soliman, Jason E Stout, Ireri Thirion-Romero, Andrea B. Troxel, Ting-Yu Tseng, Nicholas A. Turner, Robert J. Ulrich, Stephen R. Walsh, Steve A. Webb, Jesper M. Weehuizen, Maria Velinova, Hon-Lai Wong, Rebekah Wrenn, Fernando G Zampieri, Wu Zhong, David Moher, Steven N. Goodman, John P.A. Ioannidis, Lars G. Hemkens

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

18: Inward and outward effectiveness of cloth masks, a surgical mask, and a face shield
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Posted 20 Nov 2020

Inward and outward effectiveness of cloth masks, a surgical mask, and a face shield
14,095 downloads medRxiv public and global health

Jin Pan, Charbel Harb, Weinan Leng, Linsey C. Marr

We evaluated the effectiveness of 11 face coverings for material filtration efficiency, inward protection efficiency on a manikin, and outward protection efficiency on a manikin. At the most penetrating particle size, the vacuum bag, microfiber cloth, and surgical mask had material filtration efficiencies >50%, while the other materials had much lower filtration efficiencies. However, these efficiencies increased rapidly with particle size, and many materials had efficiencies >50% at 2 m and >75% at 5 m. The vacuum bag performed best, with efficiencies of 54-96% for all three metrics, depending on particle size. The thin acrylic and face shield performed worst. Inward protection efficiency and outward protection efficiency were similar for many masks; the two efficiencies diverged for stiffer materials and those worn more loosely (e.g., bandana) or more tightly (e.g., wrapped around the head) compared to a standard earloop mask. Discrepancies between material filtration efficiency and inward/outward protection efficiency indicated that the fit of the mask was important. We calculated that the particle size most likely to deposit in the respiratory tract when wearing a mask is [~]2 m. Based on these findings, we recommend a three-layer mask consisting of outer layers of a flexible, tightly woven fabric and an inner layer consisting of a material designed to filter out particles. This combination should produce an overall efficiency of >70% at the most penetrating particle size and >90% for particles 1 m and larger if the mask fits well.

19: Beyond Six Feet: A Guideline to Limit Indoor Airborne Transmission of COVID-19
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Posted 01 Sep 2020

Beyond Six Feet: A Guideline to Limit Indoor Airborne Transmission of COVID-19
13,632 downloads medRxiv public and global health

Martin Z. Bazant, John W. M. Bush

The current revival of the world's economy is being predicated on social distancing, specifically the Six-Foot Rule, a guideline that offers little protection from pathogen-bearing aerosol droplets sufficiently small to be continuously mixed through an indoor space. The importance of airborne transmission of COVID-19 is now widely recognized. While tools for risk assessment have recently been developed, no safety guideline has been proposed to protect against it. We here build upon models of airborne disease transmission in order to derive an indoor safety guideline that would impose an upper bound on the "cumulative exposure time", the product of the number of occupants and their time in an enclosed space. We demonstrate how this bound depends on the rates of ventilation and air filtration, dimensions of the room, breathing rate, respiratory activity and face-mask use of its occupants, and infectiousness of the respiratory aerosols. By synthesizing available data from the best characterized indoor spreading events with respiratory drop-size distributions, we estimate an infectious dose on the order of ten aerosol-borne virions. The new virus is thus inferred to be an order of magnitude more infectious than its forerunner (SARS-CoV), consistent with the pandemic status achieved by COVID-19. Case studies are presented for classrooms and nursing homes, and a spreadsheet and online app are provided to facilitate use of our guideline. Implications for contact tracing and quarantining are considered, appropriate caveats enumerated. Particular consideration is given to respiratory jets, which may substantially elevate risk when face masks are not worn.

20: Gut microbiota may underlie the predisposition of healthy individuals to COVID-19
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Posted 25 Apr 2020

Gut microbiota may underlie the predisposition of healthy individuals to COVID-19
13,374 downloads medRxiv public and global health

Wanglong Gou, Yuanqing Fu, Liang Yue, Geng-dong Chen, Xue Cai, Menglei Shuai, Fengzhe Xu, Xiao Yi, Hao Chen, Yi Zhu, Mian-li Xiao, Zengliang Jiang, Zelei Miao, Congmei Xiao, Bo Shen, Xiaomai Wu, Haihong Zhao, Wenhua Ling, Jun Wang, Yu-ming Chen, Tiannan Guo, Ju-Sheng Zheng

The COVID-19 pandemic is spreading globally with high disparity in the susceptibility of the disease severity. Identification of the key underlying factors for this disparity is highly warranted. Here we describe constructing a proteomic risk score based on 20 blood proteomic biomarkers which predict the progression to severe COVID-19. We demonstrate that in our own cohort of 990 individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discovered that a core set of gut microbiota could accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model, and that these gut microbiota features are highly correlated with proinflammatory cytokines in another set of 366 individuals. Fecal metabolomic analysis suggested potential amino acid-related pathways linking gut microbiota to inflammation. This study suggests that gut microbiota may underlie the predisposition of normal individuals to severe COVID-19.

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