Virological assessment of hospitalized patients with COVID-2019.
Identifieur interne : 000412 ( PubMed/Corpus ); précédent : 000411; suivant : 000413Virological assessment of hospitalized patients with COVID-2019.
Auteurs : 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 WendtnerSource :
- Nature [ 1476-4687 ] ; 2020.
Abstract
Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 20191,2. 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 lung2,4. 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 transmission6-8. 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.
DOI: 10.1038/s41586-020-2196-x
PubMed: 32235945
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Corman</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Guggemos, Wolfgang" sort="Guggemos, Wolfgang" uniqKey="Guggemos W" first="Wolfgang" last="Guggemos">Wolfgang Guggemos</name><affiliation><nlm:affiliation>Klinikum München-Schwabing, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Seilmaier, Michael" sort="Seilmaier, Michael" uniqKey="Seilmaier M" first="Michael" last="Seilmaier">Michael Seilmaier</name><affiliation><nlm:affiliation>Klinikum München-Schwabing, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Zange, Sabine" sort="Zange, Sabine" uniqKey="Zange S" first="Sabine" last="Zange">Sabine Zange</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Jones, Terry C" sort="Jones, Terry C" uniqKey="Jones T" first="Terry C" last="Jones">Terry C. Jones</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Vollmar, Patrick" sort="Vollmar, Patrick" uniqKey="Vollmar P" first="Patrick" last="Vollmar">Patrick Vollmar</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Rothe, Camilla" sort="Rothe, Camilla" uniqKey="Rothe C" first="Camilla" last="Rothe">Camilla Rothe</name><affiliation><nlm:affiliation>University Hospital LMU Munich, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Hoelscher, Michael" sort="Hoelscher, Michael" uniqKey="Hoelscher M" first="Michael" last="Hoelscher">Michael Hoelscher</name><affiliation><nlm:affiliation>University Hospital LMU Munich, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Bleicker, Tobias" sort="Bleicker, Tobias" uniqKey="Bleicker T" first="Tobias" last="Bleicker">Tobias Bleicker</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Brunink, Sebastian" sort="Brunink, Sebastian" uniqKey="Brunink S" first="Sebastian" last="Brünink">Sebastian Brünink</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Schneider, Julia" sort="Schneider, Julia" uniqKey="Schneider J" first="Julia" last="Schneider">Julia Schneider</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Ehmann, Rosina" sort="Ehmann, Rosina" uniqKey="Ehmann R" first="Rosina" last="Ehmann">Rosina Ehmann</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Zwirglmaier, Katrin" sort="Zwirglmaier, Katrin" uniqKey="Zwirglmaier K" first="Katrin" last="Zwirglmaier">Katrin Zwirglmaier</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany. christian.drosten@charite.de.</nlm:affiliation></affiliation></author><author><name sortKey="Wendtner, Clemens" sort="Wendtner, Clemens" uniqKey="Wendtner C" first="Clemens" last="Wendtner">Clemens Wendtner</name><affiliation><nlm:affiliation>Klinikum München-Schwabing, Munich, Germany. clemens.wendtner@muenchen-klinik.de.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32235945</idno><idno type="pmid">32235945</idno><idno type="doi">10.1038/s41586-020-2196-x</idno><idno type="wicri:Area/PubMed/Corpus">000412</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000412</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Virological assessment of hospitalized patients with COVID-2019.</title><author><name sortKey="Wolfel, Roman" sort="Wolfel, Roman" uniqKey="Wolfel R" first="Roman" last="Wölfel">Roman Wölfel</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Corman, Victor M" sort="Corman, Victor M" uniqKey="Corman V" first="Victor M" last="Corman">Victor M. Corman</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Guggemos, Wolfgang" sort="Guggemos, Wolfgang" uniqKey="Guggemos W" first="Wolfgang" last="Guggemos">Wolfgang Guggemos</name><affiliation><nlm:affiliation>Klinikum München-Schwabing, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Seilmaier, Michael" sort="Seilmaier, Michael" uniqKey="Seilmaier M" first="Michael" last="Seilmaier">Michael Seilmaier</name><affiliation><nlm:affiliation>Klinikum München-Schwabing, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Zange, Sabine" sort="Zange, Sabine" uniqKey="Zange S" first="Sabine" last="Zange">Sabine Zange</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Niemeyer, Daniela" sort="Niemeyer, Daniela" uniqKey="Niemeyer D" first="Daniela" last="Niemeyer">Daniela Niemeyer</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Jones, Terry C" sort="Jones, Terry C" uniqKey="Jones T" first="Terry C" last="Jones">Terry C. Jones</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Vollmar, Patrick" sort="Vollmar, Patrick" uniqKey="Vollmar P" first="Patrick" last="Vollmar">Patrick Vollmar</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Rothe, Camilla" sort="Rothe, Camilla" uniqKey="Rothe C" first="Camilla" last="Rothe">Camilla Rothe</name><affiliation><nlm:affiliation>University Hospital LMU Munich, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Hoelscher, Michael" sort="Hoelscher, Michael" uniqKey="Hoelscher M" first="Michael" last="Hoelscher">Michael Hoelscher</name><affiliation><nlm:affiliation>University Hospital LMU Munich, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Bleicker, Tobias" sort="Bleicker, Tobias" uniqKey="Bleicker T" first="Tobias" last="Bleicker">Tobias Bleicker</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Brunink, Sebastian" sort="Brunink, Sebastian" uniqKey="Brunink S" first="Sebastian" last="Brünink">Sebastian Brünink</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Schneider, Julia" sort="Schneider, Julia" uniqKey="Schneider J" first="Julia" last="Schneider">Julia Schneider</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Ehmann, Rosina" sort="Ehmann, Rosina" uniqKey="Ehmann R" first="Rosina" last="Ehmann">Rosina Ehmann</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Zwirglmaier, Katrin" sort="Zwirglmaier, Katrin" uniqKey="Zwirglmaier K" first="Katrin" last="Zwirglmaier">Katrin Zwirglmaier</name><affiliation><nlm:affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation><nlm:affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany. christian.drosten@charite.de.</nlm:affiliation></affiliation></author><author><name sortKey="Wendtner, Clemens" sort="Wendtner, Clemens" uniqKey="Wendtner C" first="Clemens" last="Wendtner">Clemens Wendtner</name><affiliation><nlm:affiliation>Klinikum München-Schwabing, Munich, Germany. clemens.wendtner@muenchen-klinik.de.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Nature</title><idno type="eISSN">1476-4687</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 2019<sup>1,2</sup>. Initial outbreaks in China involved 13.8% cases with severe, and 6.1% with critical courses<sup>3</sup>. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung<sup>2,4</sup>. 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 2003<sup>5</sup>. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting the potential for pre- or oligosymptomatic transmission<sup>6-8</sup>. 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 × 10<sup>8</sup> 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.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32235945</PMID><DateRevised><Year>2020</Year><Month>04</Month><Day>02</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1476-4687</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Apr</Month><Day>01</Day></PubDate></JournalIssue><Title>Nature</Title><ISOAbbreviation>Nature</ISOAbbreviation></Journal><ArticleTitle>Virological assessment of hospitalized patients with COVID-2019.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41586-020-2196-x</ELocationID><Abstract><AbstractText>Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection that emerged in late 2019<sup>1,2</sup>. Initial outbreaks in China involved 13.8% cases with severe, and 6.1% with critical courses<sup>3</sup>. This severe presentation corresponds to the usage of a virus receptor that is expressed predominantly in the lung<sup>2,4</sup>. 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 2003<sup>5</sup>. However, there are reports of COVID-19 cases with mild upper respiratory tract symptoms, suggesting the potential for pre- or oligosymptomatic transmission<sup>6-8</sup>. 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 × 10<sup>8</sup> 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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wölfel</LastName><ForeName>Roman</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Corman</LastName><ForeName>Victor M</ForeName><Initials>VM</Initials><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guggemos</LastName><ForeName>Wolfgang</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Klinikum München-Schwabing, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seilmaier</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Klinikum München-Schwabing, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zange</LastName><ForeName>Sabine</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Müller</LastName><ForeName>Marcel A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Niemeyer</LastName><ForeName>Daniela</ForeName><Initials>D</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-1897-6365</Identifier><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jones</LastName><ForeName>Terry C</ForeName><Initials>TC</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-1120-9531</Identifier><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vollmar</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rothe</LastName><ForeName>Camilla</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>University Hospital LMU Munich, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoelscher</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>University Hospital LMU Munich, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bleicker</LastName><ForeName>Tobias</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brünink</LastName><ForeName>Sebastian</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schneider</LastName><ForeName>Julia</ForeName><Initials>J</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-0494-1022</Identifier><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ehmann</LastName><ForeName>Rosina</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zwirglmaier</LastName><ForeName>Katrin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Bundeswehr Institute of Microbiology, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Drosten</LastName><ForeName>Christian</ForeName><Initials>C</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-7923-0519</Identifier><AffiliationInfo><Affiliation>Charité Universitätsmedizin Berlin, Berlin, Germany. christian.drosten@charite.de.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wendtner</LastName><ForeName>Clemens</ForeName><Initials>C</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-2866-2260</Identifier><AffiliationInfo><Affiliation>Klinikum München-Schwabing, Munich, Germany. clemens.wendtner@muenchen-klinik.de.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal 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