Virological assessment of hospitalized patients with COVID-2019

Roman Wölfel, Victor M. Corman, Wolfgang Guggemos, Michael Seilmaier, Sabine Zange, Marcel A. Müller, Daniela Niemeyer, Terry C. Jones, Patrick Vollmar, Camilla Rothe, Michael Hoelscher, Tobias Bleicker, Sebastian Brünink, Julia Schneider, Rosina Ehmann, Katrin Zwirglmaier, Christian Drosten () and Clemens Wendtner ()
Additional contact information
Roman Wölfel: Bundeswehr Institute of Microbiology
Victor M. Corman: Charité Universitätsmedizin Berlin
Wolfgang Guggemos: Klinikum München-Schwabing
Michael Seilmaier: Klinikum München-Schwabing
Sabine Zange: Bundeswehr Institute of Microbiology
Marcel A. Müller: Charité Universitätsmedizin Berlin
Daniela Niemeyer: Charité Universitätsmedizin Berlin
Terry C. Jones: Charité Universitätsmedizin Berlin
Patrick Vollmar: Bundeswehr Institute of Microbiology
Camilla Rothe: University Hospital LMU Munich
Michael Hoelscher: University Hospital LMU Munich
Tobias Bleicker: Charité Universitätsmedizin Berlin
Sebastian Brünink: Charité Universitätsmedizin Berlin
Julia Schneider: Charité Universitätsmedizin Berlin
Rosina Ehmann: Bundeswehr Institute of Microbiology
Katrin Zwirglmaier: Bundeswehr Institute of Microbiology
Christian Drosten: Charité Universitätsmedizin Berlin
Clemens Wendtner: Klinikum München-Schwabing

Nature, 2020, vol. 581, issue 7809, 465-469

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41586-020-2196-x

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