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      A population framework for predicting the proportion of people infected by the far-field airborne transmission of SARS-CoV-2 indoors

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          Abstract

          The number of occupants in a space influences the risk of far-field airborne transmission of SARS-CoV-2 because the likelihood of having infectious and susceptible people both correlate with the number of occupants. This paper explores the relationship between occupancy and the probability of infection, and how this affects an individual person and a population of people. Mass-balance and dose–response models determine far-field transmission risks for an individual person and a population of people after sub-dividing a large reference space into 10 identical comparator spaces.

          For a single infected person, the dose received by an individual person in the comparator space is 10 times higher because the equivalent ventilation rate per infected person is lower when the per capita ventilation rate is preserved.

          However, accounting for population dispersion, such as the community prevalence of the virus, the probability of an infected person being present and uncertainty in their viral load, shows the transmission probability increases with occupancy and the reference space has a higher transmission risk. Also, far-field transmission is likely to be a rare event that requires a high emission rate, and there are a set of Goldilocks conditions that are just right when equivalent ventilation is effective at mitigating against transmission. These conditions depend on the viral load, because when they are very high or low, equivalent ventilation has little effect on transmission risk.

          Nevertheless, resilient buildings should deliver the equivalent ventilation rate required by standards as minimum.

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          Viral load of SARS-CoV-2 in clinical samples

          An outbreak caused by a novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019, 1 and has since spread within China and to other countries. Real-time RT-PCR assays are recommended for diagnosis of SARS-CoV-2 infection. 2 However, viral dynamics in infected patients are still yet to be fully determined. Here, we report our findings from different types of clinical specimens collected from 82 infected individuals. Serial samples (throat swabs, sputum, urine, and stool) from two patients in Beijing were collected daily after their hospitalisation (patient 1, days 3–12 post-onset; patient 2, days 4–15 post-onset). These samples were examined by an N-gene-specific quantitative RT-PCR assay, as described elsewhere. 3 The viral loads in throat swab and sputum samples peaked at around 5–6 days after symptom onset, ranging from around 104 to 107 copies per mL during this time (figure A, B ). This pattern of changes in viral load is distinct from the one observed in patients with SARS, which normally peaked at around 10 days after onset. 4 Sputum samples generally showed higher viral loads than throat swab samples. No viral RNA was detected in urine or stool samples from these two patients. Figure Viral dynamics of SARS-CoV-2 in infected patients Viral load (mean [SD]) from serial throat swab and sputum samples in patient 1 (A) and patient 2 (B). (C) Viral load (median [IQR]) in throat and sputum samples collected from 80 patients at different stages after disease onset. (D) Correlation between viral load in throat swab samples and viral load in sputum samples. We also studied respiratory samples (nasal [n=1] and throat swabs [n=67], and sputum [n=42]) collected from 80 individuals at different stages of infection. The viral loads ranged from 641 copies per mL to 1·34 × 1011 copies per mL, with a median of 7·99 × 104 in throat samples and 7·52 × 105 in sputum samples (figure C). The only nasal swab tested in this study (taken on day 3 post-onset) showed a viral load of 1·69 × 105 copies per mL. Overall, the viral load early after onset was high (>1 × 106 copies per mL). However, a sputum sample collected on day 8 post-onset from a patient who died had a very high viral load (1·34 × 1011 copies per mL). Notably, two individuals, who were under active surveillance because of a history of exposure to SARS-CoV-2-infected patients showed positive results on RT-PCR a day before onset, suggesting that infected individuals can be infectious before them become symptomatic. Among the 30 pairs of throat swab and sputum samples available, viral loads were significantly correlated between the two sample types for days 1–3 (R2=0·50, p=0·022), days 4–7 (R2=0·93, p<0·001), and days 7–14 (R2=0·95, p=0·028). From 17 confirmed cases of SARS-CoV-2 infection with available data (representing days 0–13 after onset), stool samples from nine (53%; days 0–11 after onset) were positive on RT-PCR analysis. Although the viral loads were less than those of respiratory samples (range 550 copies per mL to 1·21 × 105 copies per mL), precautionary measures should be considered when handling faecal samples.
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            Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study

            Summary Background Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures. Methods From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk. Findings Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20–22). Cases were isolated on average 4·6 days (95% CI 4·1–5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1–2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49–26·33] for household contacts and 7·06 [1·43–34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1–13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3–0·5), with a mean serial interval of 6·3 days (95% CI 5·2–7·6). Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. Funding Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention.
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              SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis

              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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                Author and article information

                Journal
                Build Environ
                Build Environ
                Building and Environment
                Published by Elsevier Ltd.
                0360-1323
                1873-684X
                18 June 2022
                18 June 2022
                : 109309
                Affiliations
                [a ]Department of Architecture and Built Environment, University of Nottingham, Nottingham, UK
                [b ]Department of Infection and Global Health, School of Medicine, University of St Andrews, St Andrews, UK
                [c ]Department of Engineering, Cambridge University, Cambridge, UK
                Author notes
                [* ]Corresponding author.
                Article
                S0360-1323(22)00543-1 109309
                10.1016/j.buildenv.2022.109309
                9212805
                35757305
                7ab733a5-df09-4ddc-bacb-6f233fbef130
                Crown Copyright © 2022 Published by Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 3 February 2022
                : 9 June 2022
                : 14 June 2022
                Categories
                Article

                relative exposure index,ventilation,aerosols,transmission risk,viral load,covid-19

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