Evaluación virológica de pacientes hospitalizados con COVID-2019

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 &
• Clemens Wendtner 

Abstract

Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 2019^1,2. Initial outbreaks in China involved 13.8% cases with severe, and 6.1% with critical courses³. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung^2,4. By causing an early onset of severe symptoms, this same receptor tropism is thought to have determined pathogenicity, but also aided the control, of severe acute respiratory syndrome (SARS) in 2003⁵. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting the potential for pre- or oligosymptomatic transmission^6–8. There is an urgent need for information on body site-specific virus replication, immunity, and infectivity. Here we provide a detailed virological analysis of nine cases, providing proof of active virus replication in upper respiratory tract tissues. Pharyngeal virus shedding was very high during the first week of symptoms (peak at 7.11 × 10⁸ RNA copies per throat swab, day 4). Infectious virus was readily isolated from throat- and lung-derived samples, but not from stool samples, in spite of high virus RNA concentration. Blood and urine never yielded virus. Active replication in the throat was confirmed by viral replicative RNA intermediates in throat samples. Sequence-distinct virus populations were consistently detected in throat and lung samples from the same patient, proving independent replication. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (14 days in all), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild upper respiratory tract illness. Active virus replication in the upper respiratory tract puts the prospects of COVID-19 containment in perspective.

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Author notes

1. These authors contributed equally: Roman Wölfel, Victor M. Corman, Wolfgang Guggemos
2. These authors jointly supervised this work: Christian Drosten, Clemens Wendtner

Affiliations

1. Bundeswehr Institute of Microbiology, Munich, Germany
   • Roman Wölfel
   • , Sabine Zange
   • , Patrick Vollmar
   • , Rosina Ehmann
   •  & Katrin Zwirglmaier
2. Charité Universitätsmedizin Berlin, Berlin, Germany
   • Victor M. Corman
   • , Marcel A. Müller
   • , Daniela Niemeyer
   • , Terry C. Jones
   • , Tobias Bleicker
   • , Sebastian Brünink
   • , Julia Schneider
   •  & Christian Drosten
3. Klinikum München-Schwabing, Munich, Germany
   • Wolfgang Guggemos
   • , Michael Seilmaier
   •  & Clemens Wendtner
4. Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, UK
   • Terry C. Jones
5. University Hospital LMU Munich, Munich, Germany
   • Camilla Rothe
   •  & Michael Hoelscher

Corresponding authors

Correspondence to Christian Drosten or Clemens Wendtner.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, which include a description of RNA extraction and RT-PCR methods, a description of cell culture and antibody detection methods and Supplementary References.

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Wölfel, R., Corman, V.M., Guggemos, W. et al. Virological assessment of hospitalized patients with COVID-2019. Nature (2020). https://doi.org/10.1038/s41586-020-2196-x