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Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster
Roman Woelfel, View ORCID ProfileVictor Max Corman, Wolfgang Guggemos, Michael Seilmaier, Sabine Zange, Marcel A Mueller, Daniela Niemeyer, Patrick Vollmar, Camilla Rothe, Michael Hoelscher, Tobias Bleicker, Sebastian Bruenink, Julia Schneider, Rosina Ehmann, Katrin Zwirglmaier, Christian Drosten, Clemens Wendtner
doi: https://doi.org/10.1101/2020.03.05.20030502
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Background: In coronavirus disease 2019 (COVID-19), current case definitions presume mainly lower respiratory tract infection. However, cases seen outside the epicenter of the epidemic may differ in their overall clinical appearance due to more sensitive case finding.
Methods: We studied viral load courses by RT-PCR in oro- and nasopharyngeal swabs, sputum, stool, blood, and urine in nine hospitalized cases. Infectious virus was detected by cell culture. Active replication was demonstrated by analysis of viral subgenomic replicative intermediates. Serology including neutralization testing was done to characterize immune response.
Results: Seven cases had upper respiratory tract disease. Lower respiratory tract symptoms seen in two cases were limited. Clinical sensitivity of RT-PCR on swabs taken on days 1-5 of symptoms was 100%, with no differences comparing swab and sputum samples taken simultaneously. Average viral load was 6.76x10E5 copies per swab during the first 5 days. Live virus isolates were obtained from swabs during the first week of illness. Proof of active viral replication in upper respiratory tract tissues was obtained by detection of subgenomic viral RNA. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after about one week.
Conclusions: The present study shows that COVID-19 can often present as a common cold-like illness. SARS-CoV-2 can actively replicate in the upper respiratory tract, and is shed for a prolonged time after symptoms end, including in stool. These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This work was funded by grants from the German Ministry of Research (01KI1723A) and the European Union (602525) to C. D. as well as by the German Bundeswehr Medical ServiceBiodefense Research Program. The funders had no role in study design, data collection and analysis or decision to publish.
https://www.medrxiv.org/content/10.1....05.20030502v1
Roman Woelfel, View ORCID ProfileVictor Max Corman, Wolfgang Guggemos, Michael Seilmaier, Sabine Zange, Marcel A Mueller, Daniela Niemeyer, Patrick Vollmar, Camilla Rothe, Michael Hoelscher, Tobias Bleicker, Sebastian Bruenink, Julia Schneider, Rosina Ehmann, Katrin Zwirglmaier, Christian Drosten, Clemens Wendtner
doi: https://doi.org/10.1101/2020.03.05.20030502
This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Abstract
Background: In coronavirus disease 2019 (COVID-19), current case definitions presume mainly lower respiratory tract infection. However, cases seen outside the epicenter of the epidemic may differ in their overall clinical appearance due to more sensitive case finding.
Methods: We studied viral load courses by RT-PCR in oro- and nasopharyngeal swabs, sputum, stool, blood, and urine in nine hospitalized cases. Infectious virus was detected by cell culture. Active replication was demonstrated by analysis of viral subgenomic replicative intermediates. Serology including neutralization testing was done to characterize immune response.
Results: Seven cases had upper respiratory tract disease. Lower respiratory tract symptoms seen in two cases were limited. Clinical sensitivity of RT-PCR on swabs taken on days 1-5 of symptoms was 100%, with no differences comparing swab and sputum samples taken simultaneously. Average viral load was 6.76x10E5 copies per swab during the first 5 days. Live virus isolates were obtained from swabs during the first week of illness. Proof of active viral replication in upper respiratory tract tissues was obtained by detection of subgenomic viral RNA. Shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after about one week.
Conclusions: The present study shows that COVID-19 can often present as a common cold-like illness. SARS-CoV-2 can actively replicate in the upper respiratory tract, and is shed for a prolonged time after symptoms end, including in stool. These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This work was funded by grants from the German Ministry of Research (01KI1723A) and the European Union (602525) to C. D. as well as by the German Bundeswehr Medical ServiceBiodefense Research Program. The funders had no role in study design, data collection and analysis or decision to publish.
https://www.medrxiv.org/content/10.1....05.20030502v1