Background Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics. Methods In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914. Findings 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17•0 days (95% CI 15•5-18•6; 43 studies, 3229 individuals) in upper respiratory tract, 14•6 days (9•3-20•0; seven studies, 260 individuals) in lower respiratory tract, 17•2 days (14•4-20•1; 13 studies, 586 individuals) in stool, and 16•6 days (3•6-29•7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0•304 [95% CI 0•115-0•493]; p=0•0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10. Interpretation Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2. Funding None.

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Background: The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics and society. A wealth of data has been generated since its emergence in December 2019, and it is vital for clinicians to keep up with this data from across the world at a time of uncertainty and constantly evolving guidelines and clinical practice. Objectives: Here we provide an update for clinicians on the recent developments in the virology, diagnostics, clinical presentation, viral shedding, and treatment options for COVID-19 based on current literature. Sources: We considered published peer-reviewed papers and non-peer-reviewed pre-print manuscripts on COVID19 and related aspects with an emphasis on clinical management aspects. Content: We describe the virological characteristics of SARS-CoV-2 and the clinical course of COVID-19 with an emphasis on diagnostic challenges, duration of viral shedding, severity markers and current treatment options. Implications: The key challenge in managing COVID-19 remains patient density. However, accurate diagnosis as well as early identification and management of high-risk severe cases are important for many clinicians. For improved management of cases, there is a need to understand test probability of serology, qRT-PCR and radiological testing, and the efficacy of available treatment options that could be used in severe cases with a high risk of mortality.

Background There is limited information on the effect of age on the transmission of SARS-CoV-2 infection in different settings. Methods We reviewed published studies/data on detection of SARS-CoV-2 infection in contacts of COVID-19 cases, serological studies, and studies of infections in schools. Results Compared to younger/middle aged adults, susceptibility to infection for children aged under 10y is estimated to be significantly lower, while estimated susceptibility to infection in adults aged over 60y is higher. Serological studies suggest that younger adults (particularly those aged under 35y) often have high cumulative incidence of SARS-CoV-2 infection in the community. There is some evidence that given limited control measures, SARS-CoV-2 may spread robustly in secondary/high schools, and to a lesser degree in primary schools, with class size possibly affecting that spread. There is also evidence of more limited spread in schools when some mitigation measures are implemented. Several potential biases that may affect these studies are discussed. Conclusions Mitigation measures should be implemented when opening schools, particularly secondary/high schools. Efforts should be undertaken to diminish mixing in younger adults, particularly individuals aged 18-35y to mitigate the spread of the epidemic in the community.

Background Evidence is conflicting about how HIV modulates COVID-19. We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the ISARIC WHO CCP study. Methods We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, ten individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). Results Among 47,592 patients, 122 (0.26%) had confirmed HIV infection and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 versus 74 years; p<0.001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive vs. HIV-negative groups (26.7% vs. 32.1%; p=0.16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; p<0.001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; p=0.05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; p=0.008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; p<0.001). Conclusions HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19.

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reopening -testing -money). 31. Centers for Disease Control and Prevention. Testing in highdensity critical infrastructure workplaces. June 13, 2020 (https:// www . cdc . gov/ coronavirus/ 2019 -ncov/ community/ worker -safety -support/ hd -testing . html). 32. Levine R. The case against reopening schools: a teacher's perspective. July 14, 2020 (https://docs . google . com/ document/ d/ 1IAQndRjnya96JZOwf4HgPBBk -RwOCrtO1efSkgPIiUc/ edit). 33. Camera L. Report: no way to reopen schools safely without federal bailout. U.S. News & World Report. June 8, 2020 (https:// www . usnews . com/ news/ education -news/ articles/ 2020 -06 -08/ report -schools -need -a -federal -bailout -in -order -to -reopen).

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