Corpus overview


Overview

MeSH Disease

Transmission

Seroprevalence
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    Which policies most effectively reduce SARS-CoV-2 transmission TRANS in schools?

    Authors: Anna Bershteyn; Hae-Young Kim; Jessica B. McGillen; R. Scott Braithwaite

    doi:10.1101/2020.11.24.20237305 Date: 2020-11-27 Source: medRxiv

    Introduction New York City (NYC) has the largest public school system in the United States (US). During the SARS-CoV-2 pandemic, NYC was the first major US city to open schools for in-person learning in the 2020-2021 academic year. Several policies were implemented to reduce the risk of in-school transmission TRANS, including infection control measures (facemasks, physical distancing, enhanced indoor ventilation, cohorting of small groups, and hand hygiene), option of all-remote instruction, alternative options for how class schedules would rotate in-person and remote instruction, daily symptom screening, and testing 10-20% of students and staff weekly or monthly depending on local case rates. We sought to determine which of these policies had the greatest impact on reducing the risk of in-school transmission TRANS. Methods We evaluated the impact of each policy by referring to global benchmarks for the secondary attack rate TRANS ( SAR TRANS) of SARS-CoV-2 in school settings and by simulating the potential for transmission TRANS in NYC's rotating cohort schedules, in which teachers could act as "bridges" across rotating cohorts. We estimated the impact of (1) infection control measures, (2) providing an option of all-remote instruction, (3) choice of class scheduling for in-person learners, (4) daily symptom screening, (5) testing to curtail transmission TRANS, and (6) testing to identify school outbreaks. Each policy was assessed independently of other policies, with the exception of symptom screening and random testing, which were assessed both independently and jointly. Results Among the policies analyzed, the greatest transmission TRANS reduction was associated with the infection control measures, followed by small class cohorts with an option for all-remote instruction, symptom screening, and finally randomly testing 10-20% of school attendees. Assuming adult TRANS staff are the primary source of within-school SARS-CoV-2 transmission TRANS, weekly testing of staff could be at least as effective as symptom screening, and potentially more so if testing days occur in the beginning of the workweek with results available by the following day. A combination of daily symptom screening and testing on the first workday of each week could reduce transmission TRANS by 70%. Conclusions Adherence to infection control is the highest priority for safe school re-opening. Further transmission TRANS reduction can be achieved through small rotating class cohorts with an option for remote learning, widespread testing at the beginning of the work week, and daily symptom screening and self-isolation. Randomly testing 10-20% of attendees weekly or monthly does not meaningfully curtail transmission TRANS and may not detect outbreaks before they have spread beyond a handful of individuals. School systems considering re-opening during the SARS-CoV-2 pandemic or similarly virulent respiratory disease MESHD outbreaks should consider these relative impacts when setting policy priorities.

    Impact of non-pharmaceutical interventions for SARS-CoV-2 on norovirus outbreaks: an analysis of outbreaks reported by 9 US States

    Authors: Alicia Nicole Mullis Kraay; Peichun Han; Anita K Kambhampati; Mary E Wikswo; Sara A Mirza; Benjamin A Lopman; Halima Bello-Manga; Reward Audu; Samuel Ige; Grace Nmadu

    doi:10.1101/2020.11.25.20237115 Date: 2020-11-27 Source: medRxiv

    Importance: The impact of non-pharmaceutical interventions (NPIs) in response to the SARS-CoV-2 pandemic on incidence of other infectious diseases MESHD is still being assessed. Objective: To determine if the observed change in reported norovirus outbreaks in the United States was best explained by underreporting, seasonal trends, or reduced exposure due to NPIs. We also aimed to assess if the change in reported norovirus outbreaks varied by setting. Design: An ecologic, interrupted time series analysis of norovirus outbreaks from nine states reported to the National Outbreak Reporting System (NORS) from July 2012-July 2020. Setting: Surveillance data from Massachusetts, Michigan, Minnesota, Ohio, Oregon, South Carolina, Tennessee, Virginia, and Wisconsin were included in the analysis. Participants: 9,226 reports of acute gastroenteritis MESHD outbreaks with norovirus as an epidemiologically suspected or laboratory-confirmed etiology were included in the analysis, resulting in more than 8 years of follow up. Outbreak reports from states that participated in NoroSTAT for at least 4 years were included in the analysis (range: 4-8 years). Exposure: The main exposure of interest was time period: before (July 2012-February 2020) or after (April 2020-July 2020) the start of NPIs in the United States Main outcome: The main outcome of interest was monthly rate of reported norovirus outbreaks. As a secondary outcome, we also examined the average outbreak size. Results: We found that the decline in norovirus outbreak reports was significant for all 9 states considered (pooled incidence rate ratio (IRR) comparing April 2020-July 2020 vs. all pre-COVID months for each state= 0.14, 95% CI: 0.098, 0.21; P=<0.0001), even after accounting for typical seasonal decline MESHD in incidence during the summer months. These patterns were similar across a variety of settings, including nursing homes, child TRANS daycares, healthcare settings, and schools. The average outbreak size was also reduced by 61% (95% CI: 56%, 42.7%; P=<0.0001), suggesting that the decline does not reflect a tendency to report only more severe outbreaks due to strained surveillance systems, but instead reflects a decline in incidence. Conclusions and relevance: While NPIs implemented during the spring and summer of 2020 were intended to reduce transmission TRANS of SARS-CoV-2, these changes also appear to have impacted the incidence of norovirus, a non-respiratory pathogen. These results suggest that NPIs may provide benefit for preventing transmission TRANS of other human pathogens, reducing strain to health systems during the continued SARS-CoV-2 pandemic.

    Comparing COVID-19 MESHD vaccine allocation strategies in India: a mathematical modelling study

    Authors: Brody H Foy; Brian Wahl; Kayur Mehta; Anita Shet; Gautam I Menon; Carl D Britto; Johan Holgersson; Niklas Nielsen; Peter Bentzer; Areti Angeliki Veroniki; Lehana Thabane; Fanlong Bu; Sarah Klingenberg; Christian Gluud; Janus Christian Jakobsen; Willem Hanekom; Bernadett I Gosnell; COMMIT-KZN Team; Emily Wong; Tulio de Oliveira; Mahomed-Yunus S Moosa; Alasdair Leslie; Henrik Kloverpris; Alex Sigal

    doi:10.1101/2020.11.22.20236091 Date: 2020-11-24 Source: medRxiv

    Background: The development and widespread use of an effective SARS-CoV-2 vaccine could help prevent substantial morbidity and mortality associated with COVID-19 MESHD infection and mitigate many of the secondary effects associated with non-pharmaceutical interventions. The limited availability of an effective and licensed vaccine will task policymakers around the world, including in India, with decisions regarding optimal vaccine allocation strategies. Using mathematical modelling we aimed to assess the impact of different age TRANS-specific COVID-19 MESHD vaccine allocation strategies within India on SARS CoV-2-related mortality and infection. Methods: We used an age TRANS-structured, expanded SEIR model with social contact matrices to assess different age TRANS-specific vaccine allocation strategies in India. We used state-specific age TRANS structures and disease transmission TRANS coefficients estimated from confirmed Indian incident cases of COVID-19 MESHD between 28 January and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccinate allocation strategies based on prioritizing different age groups TRANS, and the interactions of these strategies with several concurrent non-pharmacologic interventions (i.e., social distancing, mandated masks, lockdowns). Given the uncertainty associated with current COVID-19 MESHD vaccine development, we also varied several vaccine characteristics (i.e., efficacy, type of immunity conferred, and rollout speed) in the modelling simulations. Results: In nearly all scenarios, prioritizing COVID-19 MESHD vaccine allocation for older populations (i.e., >60yrs old) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. However, preferential vaccination of this target group often produced higher total symptomatic infection counts and more pronounced estimates of peak incidence than strategies which targeted younger adults TRANS (i.e., 20-40yrs or 40-60yrs) or the general population irrespective of age TRANS. Vaccine efficacy, immunity type, target coverage and rollout speed all significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination. Conclusions: Our findings support global recommendations to prioritize COVID-19 MESHD vaccine allocation for older age groups TRANS. Including younger adults TRANS in the prioritisation group can reduce overall infection rates, although this benefit was countered by the larger mortality rates in older populations. Ultimately an optimal vaccine allocation strategy will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals such as reducing mortality, morbidity, or peak incidence.

    Loneliness among older adults TRANS in the community during COVID-19 MESHD

    Authors: Rachel D Savage; Wei Wu; Joyce Li; Andrea Lawson; Susan E Bronskill; Stephanie A. Chamberlain; Jim Grieve; Andrea Gruneir; Christina Reppas-Rindlisbacher; Nathan M. Stall; Paula A Rochon; Fanlong Bu; Sarah Klingenberg; Christian Gluud; Janus Christian Jakobsen; Willem Hanekom; Bernadett I Gosnell; COMMIT-KZN Team; Emily Wong; Tulio de Oliveira; Mahomed-Yunus S Moosa; Alasdair Leslie; Henrik Kloverpris; Alex Sigal

    doi:10.1101/2020.11.23.20237289 Date: 2020-11-24 Source: medRxiv

    Objective: Physical distancing and stay-at-home measures implemented to slow transmission TRANS of novel coronavirus disease MESHD ( COVID-19 MESHD) may intensify feelings of loneliness in older adults TRANS, especially those living alone. Our aim was to characterize the extent of loneliness in a sample of older adults TRANS living in the community and assess characteristics associated with loneliness. Design: Online cross-sectional survey between May 6 and May 19, 2020 Setting: Ontario, Canada Participants: Convenience sample of the members of a national retired educators' organization. Primary outcome measures: Self-reported loneliness, including differences between women and men. Results: 4879 respondents (71.0% women; 67.4% 65-79 years) reported that in the preceding week, 43.1% felt lonely at least some of the time, including 8.3% that felt lonely always or often. Women had increased odds of loneliness compared to men, whether living alone (adjusted Odds Ratio (aOR) 1.52 [95% Confidence Interval (CI) 1.13-2.04]) or with others (2.44 [95% CI 2.04-2.92]). Increasing age group TRANS decreased the odds of loneliness (aOR 0.69 [95% CI 0.59-0.81] 65-79 years and 0.50 [95% CI 0.39-0.65] 80+ years compared to <65 years). Living alone was associated with loneliness, with a greater association in men (aOR 4.26 [95% CI 3.15-5.76]) than women (aOR 2.65 [95% CI 2.26-3.11]). Other factors associated with loneliness included: fair or poor health (aOR 1.93 [95% CI 1.54-2.41]), being a caregiver (aOR 1.18 [95% CI 1.02-1.37]), receiving care (aOR 1.47 [95% CI 1.19-1.81]), high concern for the pandemic (aOR 1.55 [95% CI 1.31-1.84]), not experiencing positive effects of pandemic distancing measures (aOR 1.94 [95% CI 1.62-2.32]), and changes to daily routine (aOR 2.81 [95% CI 1.96-4.03]). Conclusions: While many older adults TRANS reported feeling lonely during COVID-19 MESHD, several characteristics - such as being female TRANS and living alone - increased the odds of loneliness. These characteristics may help identify priorities for targeting interventions to reduce loneliness.

    Interventions for treatment of COVID-19 MESHD: second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

    Authors: Sophie Juul; Emil Eik Nielsen; Joshua Feinberg; Faiza Siddiqui; Caroline Kamp Joergensen; Emily Barot; Johan Holgersson; Niklas Nielsen; Peter Bentzer; Areti Angeliki Veroniki; Lehana Thabane; Fanlong Bu; Sarah Klingenberg; Christian Gluud; Janus Christian Jakobsen; Willem Hanekom; Bernadett I Gosnell; COMMIT-KZN Team; Emily Wong; Tulio de Oliveira; Mahomed-Yunus S Moosa; Alasdair Leslie; Henrik Kloverpris; Alex Sigal

    doi:10.1101/2020.11.22.20236448 Date: 2020-11-24 Source: medRxiv

    Background COVID-19 MESHD is a rapidly spreading disease TRANS that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 MESHD are urgently needed. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in all age groups TRANS with COVID-19 MESHD. Methods and findings We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review was based on PRISMA and Cochrane guidelines, and our eight-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. According to the number of outcome comparisons, we adjusted our threshold for significance to p = 0.033. We used GRADE to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until November 2, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 82 randomized clinical trials enrolling a total of 40,249 participants. 81 out of 82 trials were at overall high risk of bias. Meta-analyses showed no evidence of a difference between corticosteroids versus control on all-cause mortality (risk ratio [RR] 0.89; 95% confidence interval [CI] 0.79 to 1.00; p = 0.05; I2 = 23.1%; eight trials; very low certainty), on serious adverse events (RR 0.89; 95% CI 0.80 to 0.99; p = 0.04; I2 = 39.1%; eight trials; very low certainty), and on mechanical ventilation (RR 0.86; 95% CI 0.55 to 1.33; p = 0.49; I2 = 55.3%; two trials; very low certainty). The fixed-effect meta-analyses showed indications of beneficial effects. Trial sequential analyses showed that the required information size for all three analyses was not reached. Meta-analysis (RR 0.93; 95% CI 0.82 to 1.07; p = 0.31; I2 = 0%; four trials; moderate certainty) and trial sequential analysis (boundary for futility crossed) showed that we could reject that remdesivir versus control reduced the risk of death MESHD by 20%. Meta-analysis (RR 0.82; 95% CI 0.68 to 1.00; p = 0.05; I2 = 38.9%; four trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of difference between remdesivir versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of remdesivir on serious adverse events. Meta-analysis (RR 0.40; 95% CI 0.19 to 0.87; p = 0.02; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of intravenous immunoglobulin versus control on all-cause mortality, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analysis (RR 0.63; 95% CI 0.35 to 1.14; p = 0.12; I2 = 77.4%; five trials; very low certainty) and trial sequential analysis (required information size not reached) showed no evidence of a difference between tocilizumab versus control on serious adverse events. Fixed-effect meta-analysis showed indications of a beneficial effect of tocilizumab on serious adverse events. Meta-analysis (RR 0.70; 95% CI 0.51 to 0.96; p = 0.02; I2 = 0%; three trials; very low certainty) showed evidence of a beneficial effect of tocilizumab versus control on mechanical ventilation, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm of reject realistic intervention effects. Meta-analysis (RR 0.32; 95% CI 0.15 to 0.69; p < 0.00; I2 = 0%; two trials; very low certainty) showed evidence of a beneficial effect of bromhexidine versus standard care on non-serious adverse events, but trial sequential analysis (required information size not reached) showed that the result was severely underpowered to confirm or reject realistic intervention effects. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that hydroxychloroquine versus control reduced the risk of death MESHD and serious adverse events by 20%. Meta-analyses and trial sequential analyses (boundary for futility crossed) showed that we could reject that lopinavir-ritonavir versus control reduced the risk of death MESHD, serious adverse events, and mechanical ventilation by 20%. All remaining outcome comparisons showed that we did not have enough information to confirm or reject realistic intervention effects. Nine single trials showed statistically significant results on our outcomes, but were underpowered to confirm or reject realistic intervention effects. Due to lack of data, it was not relevant to perform network meta-analysis or possible to perform individual patient data meta-analyses. Conclusions No evidence-based treatment for COVID-19 MESHD currently exists. Very low certainty evidence indicates that corticosteroids might reduce the risk of death MESHD, serious adverse events, and mechanical ventilation; that remdesivir might reduce the risk of serious adverse events; that intraveneous immunoglobin might reduce the risk of death MESHD and serious adverse events; that tocilizumab might reduce the risk of serious adverse events and mechanical ventilation; and that bromhexidine might reduce the risk of non-serious adverse events. More trials with low risks of bias and random errors are urgently needed. This review will continuously inform best practice in treatment and clinical research of COVID-19 MESHD.

    The potential impact of School Closure Relative to Community-based Non-pharmaceutical Interventions on COVID-19 MESHD Cases in Ontario, Canada

    Authors: David MJ Naimark; Sharmistha Mishra; Kali Barrett; Yasin Khan; Stephen Mac; Raphael Ximenes; Beate Sander; Gislaine Curty; Pedro Santos de Carvalho; Lewis F Buss; Silvia F Costa; Flavia Mendes da Cunha Carvalho; Joyce Kawakami; Noemi Nosomi Taniwaki; Heuder Paiao; Joao Carlos da Silva Bizario; Jaqueline Goes de Jesus; Ester Cerdeira Sabino; Camila Malta Romano; Regina Maura Zetone Grepan; Antonio Sesso

    doi:10.1101/2020.11.18.20234351 Date: 2020-11-20 Source: medRxiv

    ImportanceResurgent COVID-19 MESHD cases have resulted in the re-institution of nonpharmaceutical interventions, including school closure, which can have adverse effects on families. Understanding the impact of schools on the number of incident and cumulative COVID-19 MESHD cases is critical for decision-making. ObjectiveTo determine the quantitative effect of schools being open or closed relative TRANS to community-based nonpharmaceutical interventions on the number of COVID-19 MESHD cases. DesignAn agent-based transmission TRANS model. SettingA synthetic population of one million individuals based on the characteristics of the population of Ontario, Canada. ParticipantsMembers of the synthetic population clustered into households, neighborhoods or rural districts, cities or a rural region, day care facilities, classrooms - primary, elementary or high school, colleges or universities and workplaces. ExposureSchool reopening on September 15, 2020, versus schools remaining closed under different scenarios for nonpharmaceutical interventions. Main Outcome and MeasuresIncident and cumulative COVID-19 MESHD cases between September 1, 2020 and October 31, 2020. ResultsThe percentage of infections among students and teachers acquired within schools was less than 5% across modelled scenarios. Incident case numbers on October 31, 2020, were 4,414 (95% credible interval, CrI: 3,491, 5,382) and 4,740 (95% CrI 3,863, 5,691), for schools remaining closed versus reopening, respectively, with no other community-based nonpharmaceutical intervention; 714 (95%, CrI: 568, 908) and 780 (95% CrI 580, 993) for schools remaining closed versus reopening, respectively, with community-based nonpharmaceutical interventions implemented; 777 (95% credible CrI: 621, 993) and 803 (95% CrI 617, 990) for schools remaining closed versus reopening, respectively, applied to the observed case numbers in Ontario in early October 2020. Contrasting the scenarios with implementation of community-based interventions versus not doing so yielded a mean difference of 39,355 cumulative COVID-19 MESHD cases by October 31, 2020, while keeping schools closed versus reopening them yielded a mean difference of 2,040 cases. Conclusions and relevanceOur simulations suggest that the majority of COVID-19 MESHD infections in schools were due to acquisition in the community rather than transmission TRANS within schools and that the effect of school reopening on COVID-19 MESHD case numbers is relatively small compared to the effects of community-based nonpharmaceutical interventions. KEY POINTSO_ST_ABSQuestionC_ST_ABSWith resurgence of COVID-19 MESHD, reinstitution of school closure remains a possibility. Given the harm that closures can cause to children TRANS and families, the expected quantitative effect of school reopening or closure on incident and cumulative COVID-19 MESHD case numbers is an important consideration. FindingRelative to community-based nonpharmaceutical interventions, school closure resulted in a small change in COVID-19 MESHD incidence trajectories and cumulative case counts. MeaningCommunity-based interventions should take precedence over school closure.

    Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected MESHD patients.

    Authors: Florencia A.T. Boshier; Juanita Pang; Justin Penner; Joseph Hughes; Matthew Parker; James G Shepherd; Nele Alders; Alasdair Bamford; Louis Grandjean; Stephanie Grunewald; James Hatcher; Timothy Best; Caroline Dalton; Patricia Dyal Bynoe; Claire Frauenfelder; Jutta Koeglmeier; Phoebe Myerson; Sunando Roy; Rachel Williams; - The COVID-19 Genomics UK (COG-UK) Consortium; Emma C Thomson; Thushan I de Silva; Richard A Goldstein; Judith Breuer; Koen Sandra; Surya Gupta; Nicolas Drouin; Amy Harms; Thomas Hankemeier; Donald Jones; Pankaj Gupta; Cathy Lane; Said El Ouadi; Jean-Baptiste Vincendet; Nick Morrice; S. Oehrle; Nikunj Tanna; Steve Silvester; Sally Hannam; Florian Sigloch; Andrea Bhangu-Uhlmann; Jan Claereboudt; Morteza Razavi; Norman Leigh Anderson; Sven Degroeve; Lize Cuypers; Christophe Stove; Katrien Lagrou; Geert Antoine Martens; Dieter Deforce; Lennart Martens; Hans Vissers; Maarten Dhaenens; Mariano Aizpurua; Romina Zadoff; Carla Marchionatti; Natalia Garcia Escude; Romina Romero; Noelia Iraizos; Emmanuel Ezequiel Valls; Patricia Rearte Carvalho; Jimena Franco; Natali Estrada; Juan Rusconi; Guido Ochoa; Maria Veronica Paz; Patricia Lesch; Maria Fernanda Caracciolo; Maria Eugenia Macaneo; Lia Pocket; Silvana Marquez; Gaston Pellegrino; Jorge Geffner; Rocio Zarlenga; Camila Witteveen; Agustina Venditti; Indira Pichetto Olanda; Juan Mauricio Vargas; Micaela Piani; Daniela Carolina Galnarez; Florencia De la Fuente; Andrea Gamarnik; Maria del Carmen Nigro; Susana Villaroel; Cristina Soler Riera; Leonel Langellotti; Clarisa Taffarel; Jose L Scapellato; Mariano Girasolli; Maximiliano de Zan; Juan Sebastian Riera; Enio Garcia; Mario Rovere; Juan Canela; Agostina Pagella; Cecilia Pampuro; Yanina Miragaya; Silvina Kuperman; Alfonso Raggio; Ramiro Manuel Larrea; Maria Dolores Silveyra; Gabriela Leberzstein; Alejandra Debonis; Juan Molinos; Miguel Gonzalez; Eduardo Perez; Nicolas Kreplak; Susana Pastor Arguello; Luz Gibbons; Fernando Althabe; Eduardo Bergel; Fernando P Polack

    doi:10.1101/2020.11.18.20230599 Date: 2020-11-20 Source: medRxiv

    While changes in SARS-CoV-2 viral load over time have been documented, detailed information on the impact of remdesivir and how it might alter intra-host viral evolution is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 recovered from the upper respiratory tract of hospitalised children TRANS revealed that remdesivir treatment suppressed viral RNA levels in one patient but not in a second infected with an identical strain. Evidence of drug resistance to explain this difference was not found. Reduced levels of subgenomic (sg) RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication that is independent of viral RNA levels. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. We conclude that these are likely to have arisen from within-host evolution, and not co- transmission TRANS, although superinfection cannot be excluded in one case. Sample-to-sample heterogeneity in the abundances of variant genotypes is best explained by the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalisation is well described in serious lung infections MESHD caused by influenza and Mycobacterium tuberculosis MESHD and has been associated with poor drug penetration, suboptimal treatment and drug resistance. Our data provide evidence that remdesivir is able to suppress SARS-CoV-2 replication in vivo but that its efficacy may be compromised by factors reducing penetration into the lung. Based on data from influenza and Mycobacterium tuberculosis lung infections MESHD we conclude that early use of remdesivir combined with other agents should now be evaluated. Summary SentenceDeep sequencing of longitudinal samples from SARS-CoV-2 infected paediatric patients identifies evidence of remdesivir-associated inhibition of viral replication in vivo and uncovers evidence of within host evolution of distinct viral genotypes.

    Early chains of transmission TRANS of COVID-19 MESHD in France

    Authors: Juliette Paireau; Alexandra Mailles; Catherine Eisenhauer; Franck de Laval; Francois Delon; Paolo Bosetti; Henrik Salje; Valerie Ponties; Simon Cauchemez; Liam J Peck; Thomas G Ritter; Zoe de Toledo; Laura Warren; David Axten; Richard J Cornall; E Yvonne Jones; David I Stuart; Gavin Screaton; Daniel Ebner; Sarah Hoosdally; Meera Chand; - Oxford University Hospitals Staff Testing Group; Derrick W Crook; Christopher P Conlon; Koen B Pouwels; A Sarah Walker; Tim EA Peto; Susan Hopkins; Tim M Walker; Katie Jeffery; David W Eyre; Talat Mokhtari-Azad; Reza Najafipour; Reza Malekzadeh; Kimia Kahrizi; Seyed Mohammad Jazayeri; Hossein Najmabadi

    doi:10.1101/2020.11.17.20232264 Date: 2020-11-19 Source: medRxiv

    IntroductionSARS-CoV-2, which causes COVID-19 MESHD, has spread rapidly across the world. A dedicated surveillance system was implemented in France in January 2020 to improve early detection of cases and their contacts and limit secondary transmission TRANS. Our objective was to use contact-tracing TRANS data collected during this initial phase of the epidemic to better characterize SARS-CoV-2 transmission TRANS. MethodsWe analysed data collected during contact tracing TRANS and retrospective epidemiological investigations in France from 24 January to 30 March 2020. We assessed the secondary clinical attack rate TRANS and characterized the risk of a contact becoming a case. We described chains of transmission TRANS and estimated key parameters of spread. ResultsOver the study period, 6,082 contacts of 735 confirmed cases TRANS were traced TRANS. The overall secondary clinical attack rate TRANS was 4.1% (95%CI 3.6-4.6) and increased with age TRANS of the index case and of the contact. Family contacts were at higher risk of becoming cases (adjusted odds ratio 2.1 (95%CI 1.4-3.0)) while nosocomial contacts were at lower risk (adjusted odds ratio 0.3 (95%CI 0.1-0.7)), compared to coworkers/ friends TRANS. We identified 328 infector/infectee pairs, 49% of which were family members TRANS. The distribution of secondary cases TRANS was highly over-dispersed with 80% of secondary cases TRANS being caused by 10% of cases. The mean serial interval TRANS was 5.1 days (interquartile range 2-8 days) in contact-tracing TRANS pairs where late transmission TRANS events may be censored, and 6.8 (3-8) days in pairs investigated retrospectively. ConclusionThis study contributes to improving our knowledge of SARS-CoV-2 transmission TRANS, such as the importance of superspreading events. Contact-tracing TRANS data are challenging to collect but are key to better understand emerging pathogens. Funding statementThis work was supported by the LabEx "Integrative Biology of Emerging Infectious Diseases (IBEID)" (Grant Number ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Unions Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).

    Knowledge and perceptions on COVID-19 MESHD among Senior High School students in Ghana: a cross-sectional study

    Authors: Isaac Bador kamal Lettor; Paschal Awingura Apanga; Maxwell Tii Kumbeni; Ramatu Akunvane; Robert Akparibo; Paolo Bosetti; Henrik Salje; Valerie Ponties; Simon Cauchemez; Liam J Peck; Thomas G Ritter; Zoe de Toledo; Laura Warren; David Axten; Richard J Cornall; E Yvonne Jones; David I Stuart; Gavin Screaton; Daniel Ebner; Sarah Hoosdally; Meera Chand; - Oxford University Hospitals Staff Testing Group; Derrick W Crook; Christopher P Conlon; Koen B Pouwels; A Sarah Walker; Tim EA Peto; Susan Hopkins; Tim M Walker; Katie Jeffery; David W Eyre; Talat Mokhtari-Azad; Reza Najafipour; Reza Malekzadeh; Kimia Kahrizi; Seyed Mohammad Jazayeri; Hossein Najmabadi

    doi:10.1101/2020.11.18.20234088 Date: 2020-11-19 Source: medRxiv

    BackgroundThe COVID-19 pandemic MESHD is associated with high morbidity and mortality. In Ghana, policy interventions have been implemented by the Government to combat the pandemic. However, the knowledge and perceptions of Senior High School students are not investigated on the COVID-19 MESHD symptoms, transmission TRANS and the government policy measures. ObjectivesThe present study surveyed senior high school students to assess their knowledge and perceptions of COVID-19 MESHD and the government policy measures to address the outbreak. MethodsThe study employed a descriptive cross-sectional study design to assess the knowledge and perceptions of senior high school students on the COVID-19 pandemic MESHD and the measures put in place to address it. 624 senior high school students aged TRANS 18 years old and above were surveyed. Descriptive analysis was performed to assess knowledge and perceptions of COVID-19 MESHD symptoms, mode of transmissions TRANS and prevention. FindingsMost students were knowledgeable about COVID-19 MESHD symptoms, transmission TRANS and preventive measures. Majority of the students obtained information about COVID-19 MESHD from television, radio, social media, and from family and friends TRANS. Overall, the students also demonstrated a positive perception towards COVID-19 MESHD mode of transmission TRANS and preventive measures. ConclusionsOverall, senior high school students in the Bawku Municipality in Ghana demonstrated an appreciable level of knowledge and positive perception of COVID-19 MESHD. Students cited television, radio, peer education and social media as their information sources for COVID-19 MESHD. These media outlets should be prioritized in disseminating COVID 19 information to the public, especially students.

    SARS-CoV-2 epidemic MESHD after social and economic reopening in three US states reveals shifts in age TRANS structure and clinical characteristics

    Authors: Nathan Wikle; Thu Nguyen-Anh Tran; Bethany Gentilesco; Scott M Leighow; Joseph Albert; Emily R Strong; Karel Brinda; Haider Inam; Fuhan Yang; Sajid Hossain; Philip Chan; William P Hanage; Maria Messick; Justin R Pritchard; Ephraim M Hanks; Maciej F Boni; David Chien Boon Lye; Christine Cheung; Sam T Douthwaite; Gaia Nebbia; Jonathan D Edgeworth; Ali R Awan; - The COVID-19 Genomics UK (COG-UK) consortium

    doi:10.1101/2020.11.17.20232918 Date: 2020-11-18 Source: medRxiv

    In the United States, state-level re-openings in spring 2020 presented an opportunity for the resurgence of SARS-CoV-2 transmission TRANS. One important question during this time was whether human contact and mixing patterns could increase gradually without increasing viral transmission TRANS, the rationale being that new mixing patterns would likely be associated with improved distancing, masking, and hygiene practices. A second key question to follow during this time was whether clinical characteristics of the epidemic would improve after the initial surge of cases. Here, we analyze age TRANS-structured case, hospitalization, and death time series from three states - Rhode Island, Massachusetts, and Pennsylvania - that had successful re-openings in May 2020 without summer waves of infection. Using a Bayesian inference framework on eleven daily data streams and flexible daily population contact parameters, we show that population-average TRANS mixing rates dropped by >50% during the lockdown period in March/April, and that the correlation between overall population mobility and transmission TRANS-capable mobility was broken in May as these states partially re-opened. We estimate the reporting rates (fraction of symptomatic cases reporting to health system) at 96.0% (RI), 72.1% (MA), and 75.5% (PA); in Rhode Island, when accounting for cases caught through general-population screening programs, the reporting rate estimate is 94.5%. We show that elderly TRANS individuals were less able to reduce contacts during the lockdown period when compared to younger individuals, leading to the outbreak being concentrated in elderly TRANS congregate settings despite the lockdown. Attack rate TRANS estimates through August 31 2020 are 6.4% (95% CI: 5.8% - 7.3%) of the total population infected for Rhode Island, 5.7% (95% CI: 5.0% - 6.8%) in Massachusetts, and 3.7% (95% CI: 3.1% - 4.5%) in Pennsylvania, with some validation available through published seroprevalence SERO studies. Infection fatality rates (IFR) estimates are higher in our analysis (>2%) than previously reported values, likely resulting from the epidemics in these three states affecting the most vulnerable sub-populations, especially the most vulnerable of the [≥]80 age group TRANS. We make several suggestions for enhancements to current data collection practices that could improve response efforts in winter.

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MeSH Disease
Transmission
Seroprevalence


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