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      The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission

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          Abstract

          Speech droplets generated by asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are increasingly considered to be a likely mode of disease transmission. Highly sensitive laser light scattering observations have revealed that loud speech can emit thousands of oral fluid droplets per second. In a closed, stagnant air environment, they disappear from the window of view with time constants in the range of 8 to 14 min, which corresponds to droplet nuclei of ca. 4 μm diameter, or 12- to 21-μm droplets prior to dehydration. These observations confirm that there is a substantial probability that normal speaking causes airborne virus transmission in confined environments.

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          Virological assessment of hospitalized patients with COVID-2019

          Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
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            Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

            To the Editor: The novel coronavirus (2019-nCoV) from Wuhan is currently causing concern in the medical community as the virus is spreading around the world. 1 Since identification of the virus in late December 2019, the number of cases from China that have been imported into other countries is on the rise, and the epidemiologic picture is changing on a daily basis. We are reporting a case of 2019-nCoV infection acquired outside Asia in which transmission appears to have occurred during the incubation period in the index patient. A 33-year-old otherwise healthy German businessman (Patient 1) became ill with a sore throat, chills, and myalgias on January 24, 2020. The following day, a fever of 39.1°C (102.4°F) developed, along with a productive cough. By the evening of the next day, he started feeling better and went back to work on January 27. Before the onset of symptoms, he had attended meetings with a Chinese business partner at his company near Munich on January 20 and 21. The business partner, a Shanghai resident, had visited Germany between January 19 and 22. During her stay, she had been well with no signs or symptoms of infection but had become ill on her flight back to China, where she tested positive for 2019-nCoV on January 26 (index patient in Figure 1) (see Supplementary Appendix, available at NEJM.org, for details on the timeline of symptom development leading to hospitalization). On January 27, she informed the company about her illness. Contact tracing was started, and the above-mentioned colleague was sent to the Division of Infectious Diseases and Tropical Medicine in Munich for further assessment. At presentation, he was afebrile and well. He reported no previous or chronic illnesses and had no history of foreign travel within 14 days before the onset of symptoms. Two nasopharyngeal swabs and one sputum sample were obtained and were found to be positive for 2019-nCoV on quantitative reverse-transcriptase–polymerase-chain-reaction (qRT-PCR) assay. 2 Follow-up qRT-PCR assay revealed a high viral load of 108 copies per milliliter in his sputum during the following days, with the last available result on January 29. On January 28, three additional employees at the company tested positive for 2019-nCoV (Patients 2 through 4 in Figure 1). Of these patients, only Patient 2 had contact with the index patient; the other two patients had contact only with Patient 1. In accordance with the health authorities, all the patients with confirmed 2019-nCoV infection were admitted to a Munich infectious diseases unit for clinical monitoring and isolation. So far, none of the four confirmed patients show signs of severe clinical illness. This case of 2019-nCoV infection was diagnosed in Germany and transmitted outside Asia. However, it is notable that the infection appears to have been transmitted during the incubation period of the index patient, in whom the illness was brief and nonspecific. 3 The fact that asymptomatic persons are potential sources of 2019-nCoV infection may warrant a reassessment of transmission dynamics of the current outbreak. In this context, the detection of 2019-nCoV and a high sputum viral load in a convalescent patient (Patient 1) arouse concern about prolonged shedding of 2019-nCoV after recovery. Yet, the viability of 2019-nCoV detected on qRT-PCR in this patient remains to be proved by means of viral culture. Despite these concerns, all four patients who were seen in Munich have had mild cases and were hospitalized primarily for public health purposes. Since hospital capacities are limited — in particular, given the concurrent peak of the influenza season in the northern hemisphere — research is needed to determine whether such patients can be treated with appropriate guidance and oversight outside the hospital.
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              Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals

              The ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly on a global scale. Although it is clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through human respiratory droplets and direct contact, the potential for aerosol transmission is poorly understood1-3. Here we investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the outbreak of COVID-19 in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols that was detected in isolation wards and ventilated patient rooms was very low, but it was higher in the toilet areas used by the patients. Levels of airborne SARS-CoV-2 RNA in the most public areas was undetectable, except in two areas that were prone to crowding; this increase was possibly due to individuals infected with SARS-CoV-2 in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions that showed peaks in the submicrometre and/or supermicrometre regions; however, these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted through aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.
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                Author and article information

                Journal
                Proc Natl Acad Sci U S A
                Proc. Natl. Acad. Sci. U.S.A
                pnas
                pnas
                PNAS
                Proceedings of the National Academy of Sciences of the United States of America
                National Academy of Sciences
                0027-8424
                1091-6490
                2 June 2020
                13 May 2020
                13 May 2020
                : 117
                : 22
                : 11875-11877
                Affiliations
                [1] aLaboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892-0520;
                [2] bPerelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104
                Author notes
                1To whom correspondence may be addressed. Email: bax@ 123456nih.gov or philip.anfinrud@ 123456nih.gov .

                Edited by Axel T. Brunger, Stanford University, Stanford, CA, and approved May 4, 2020 (received for review April 10, 2020)

                Author contributions: C.E.B., A.B., and P.A. designed research; V.S., A.B., and P.A. performed research; V.S. analyzed data; and C.E.B., A.B., and P.A. wrote the paper.

                Author information
                http://orcid.org/0000-0002-7202-6846
                http://orcid.org/0000-0003-1319-3318
                http://orcid.org/0000-0002-9809-5700
                Article
                202006874
                10.1073/pnas.2006874117
                7275719
                32404416
                6433d998-39fe-464d-a942-28d177d50f50
                Copyright © 2020 the Author(s). Published by PNAS.

                This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

                History
                Page count
                Pages: 3
                Funding
                Funded by: HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 100000062
                Award ID: DK075141
                Award Recipient : Adriaan Bax
                Categories
                524
                530
                Biological Sciences
                Medical Sciences
                Brief Report
                Custom metadata
                free

                covid-19,speech droplet,independent action hypothesis,respiratory disease,disease transmission

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