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Virological assessment of hospitalized patients with COVID-2019.
Nature. 2020 05; 581(7809):465-469.Nat

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Wölfel R
Bundeswehr Institute of Microbiology, Munich, Germany.
Corman VM
Charité Universitätsmedizin Berlin, Berlin, Germany.
Guggemos W
Klinikum München-Schwabing, Munich, Germany.
Seilmaier M
Klinikum München-Schwabing, Munich, Germany.
Zange S
Bundeswehr Institute of Microbiology, Munich, Germany.
Müller MA
Charité Universitätsmedizin Berlin, Berlin, Germany.
Niemeyer D
Charité Universitätsmedizin Berlin, Berlin, Germany.
Jones TC
Charité Universitätsmedizin Berlin, Berlin, Germany. Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, UK.
Vollmar P
Bundeswehr Institute of Microbiology, Munich, Germany.
Rothe C
University Hospital LMU Munich, Munich, Germany.
Hoelscher M
University Hospital LMU Munich, Munich, Germany.
Bleicker T
Charité Universitätsmedizin Berlin, Berlin, Germany.
Brünink S
Charité Universitätsmedizin Berlin, Berlin, Germany.
Schneider J
Charité Universitätsmedizin Berlin, Berlin, Germany.
Ehmann R
Bundeswehr Institute of Microbiology, Munich, Germany.
Zwirglmaier K
Bundeswehr Institute of Microbiology, Munich, Germany.
Drosten C
Charité Universitätsmedizin Berlin, Berlin, Germany. christian.drosten@charite.de.
Wendtner C
Klinikum München-Schwabing, Munich, Germany. clemens.wendtner@muenchen-klinik.de.

MeSH

Antibodies, ViralBase SequenceBetacoronavirusBloodCOVID-19COVID-19 TestingClinical Laboratory TechniquesCoronavirus Envelope ProteinsCoronavirus InfectionsFecesHospitalizationHumansImmunoglobulin GImmunoglobulin MLungPandemicsPharynxPneumonia, ViralPolymorphism, Single NucleotideRNA, ViralSARS-CoV-2SeroconversionSputumUrineViral Envelope ProteinsViral LoadVirus ReplicationVirus Shedding

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32235945

Clinical Trial Links

COVID-19 Antibody Responses In Cystic Fibrosis
COVID-19 Detection Tests in Different Body Fluids
Quality of Life and Physical Performance After Novel Coronavirus Infection (COVID-19);

Citation

Wölfel, Roman, et al. "Virological Assessment of Hospitalized Patients With COVID-2019." Nature, vol. 581, no. 7809, 2020, pp. 465-469.
Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465-469.
Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., Niemeyer, D., Jones, T. C., Vollmar, P., Rothe, C., Hoelscher, M., Bleicker, T., Brünink, S., Schneider, J., Ehmann, R., Zwirglmaier, K., Drosten, C., & Wendtner, C. (2020). Virological assessment of hospitalized patients with COVID-2019. Nature, 581(7809), 465-469. https://doi.org/10.1038/s41586-020-2196-x
Wölfel R, et al. Virological Assessment of Hospitalized Patients With COVID-2019. Nature. 2020;581(7809):465-469. PubMed PMID: 32235945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Virological assessment of hospitalized patients with COVID-2019. AU - Wölfel,Roman, AU - Corman,Victor M, AU - Guggemos,Wolfgang, AU - Seilmaier,Michael, AU - Zange,Sabine, AU - Müller,Marcel A, AU - Niemeyer,Daniela, AU - Jones,Terry C, AU - Vollmar,Patrick, AU - Rothe,Camilla, AU - Hoelscher,Michael, AU - Bleicker,Tobias, AU - Brünink,Sebastian, AU - Schneider,Julia, AU - Ehmann,Rosina, AU - Zwirglmaier,Katrin, AU - Drosten,Christian, AU - Wendtner,Clemens, Y1 - 2020/04/01/ PY - 2020/03/01/received PY - 2020/03/24/accepted PY - 2020/4/3/pubmed PY - 2020/6/3/medline PY - 2020/4/3/entrez SP - 465 EP - 469 JF - Nature JO - Nature VL - 581 IS - 7809 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32235945/Virological_assessment_of_hospitalized_patients_with_COVID_2019_ DB - PRIME DP - Unbound Medicine ER -