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      Aerosol Transmission of SARS-CoV-2: Inhalation as well as Exhalation Matters for COVID-19

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          Abstract

          To the Editor: We read with great interest the article by Echternach and colleagues (1) on the topic of aerosol dispersion during singing and speaking as a potential coronavirus disease (COVID-19) transmission pathway. In the article, as has been the case more broadly regarding this mode of transmission, attention has focused on factors that influence the emission of virus (i.e., aerosol production by the infected individual) when singing or speaking. However, the ventilatory pattern of individuals exposed to the aerosolized virus is also an important factor, as this is likely to be a key modulator of the “dose” of virus-containing aerosol inhaled. As such, the inclusion of such parameters in discussion regarding aerosol transmission is important when considering why certain contexts such as choirs, restaurants, and bars, where speaking, singing, and shouting are common, have been linked to infection clusters (2). Such an appreciation may reframe the discussion to include “superreceptiveness” as a component of “superspreader” events. Ventilatory parameters vary greatly depending on both the type and intensity of activity and should feature more prominently when considering aerosol transmission. We recently investigated the physiological demands of “Singing for Lung Health” in healthy volunteers (3) and found that when participating in the singing component of the protocol, V . e increased from resting volumes of 11 (9–13) L/min (median, interquartile range [IQR]) to 22.42 L/min (IQR, 16.83–30.54 L/min), and the median volume per breath increased from 0.69 L (IQR, 0.63–0.77 L) to 2.11 L (IQR, 1.92–2.70 L). Other researchers, comparing talking with quiet breathing, found increases in parameters including V . e, Vt, and breathing frequency (4, 5). Both increased V . e and increased Vt are likely to be relevant to aerosol transmission. First, the more aerosolized viral particles inhaled the larger the inoculum, which will impact the chance of developing a disease, and may also influence disease severity (6). Second, greater inhalation will increase the alveolar area exposed to virus-containing aerosols, which may have implications for the viral processing and the immune response (7). Considering patterns of inhalation as well as exhalation should enable a more complete appreciation of context-specific viral transmission dynamics. This is particularly relevant to contexts in which V . e is increased because of physical activity (gyms, supermarkets, etc.) but also where groups of people are vocalizing, such as choral singing, restaurants, bars, and sports crowds. Appreciating these factors does not change the fundamental focus of mitigation measures of hygiene, face coverings, physical distance, and avoiding contexts with poor ventilation. However, given these considerations, particularly with new more infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in circulation, there may now be a stronger argument for face coverings that reduce the risk of inhaling aerosols rather than just reducing their emission, especially in contexts in which people are vocalizing or exercising or other risk factors are present.

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          Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in nearly 1,000,000 laboratory-confirmed cases including over 50,000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently cause asymptomatic infections. However, the underlying mechanism that confers these viral characteristics on high transmissibility and asymptomatic infection remain incompletely understood. Methods We comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison. Results SARS-CoV-2 infected and replicated in human lung tissues more efficiently than that of SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20 folds more infectious virus particles than that of SARS-CoV from the infected lung tissues (P<0.024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes, and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative pro-inflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently. Conclusions Our study provided the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provided important insights on the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.
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            Two metres or one: what is the evidence for physical distancing in covid-19?

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              Inoculum at the time of SARS-CoV-2 exposure and risk of disease severity

              Highlights • A relationship between infecting dose and risk of disease severity has not been demonstrated for COVID-19. • We report three clusters of COVID-19 in Madrid, in which infected persons experienced different disease severity according to distinct sizes of viral inoculum. • Smaller viral inoculi as a result of wide social distancing would contribute to the lower pathogenicity of recent SARS-CoV-2 infections.
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                Author and article information

                Journal
                Am J Respir Crit Care Med
                Am J Respir Crit Care Med
                ajrccm
                American Journal of Respiratory and Critical Care Medicine
                American Thoracic Society
                1073-449X
                1535-4970
                15 April 2021
                15 April 2021
                15 April 2021
                15 April 2021
                : 203
                : 8
                : 1041-1042
                Affiliations
                [ 1 ]Imperial College London

                London, United Kingdom
                [ 2 ]Royal Brompton and Harefield National Health Service Foundation Trust

                London, United Kingdom
                [ 3 ]Brunel University

                London, United Kingdom

                and
                [ 4 ]University College London

                London, United Kingdom
                Author notes
                [* ]Corresponding author (e-mail: k.philip@ 123456imperial.ac.uk ).
                Author information
                http://orcid.org/0000-0001-9614-3580
                Article
                202012-4445LE
                10.1164/rccm.202012-4445LE
                8048753
                33529544
                ad35e8dd-919b-4cbf-b4b4-b1b71da30d47
                Copyright © 2021 by the American Thoracic Society

                This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 ( https://creativecommons.org/licenses/by-nc-nd/4.0/). For commercial usage and reprints, please contact Diane Gern ( dgern@ 123456thoracic.org ).

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