Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

Jeroen van Kampen; David van de Vijver; Pieter Fraaij; Bart Haagmans; Mart Lamers; Nisreen Okba; Johan van den Akker; Rik Endeman; Diederik Gommers; Jan Cornelissen; R.A.S. Hoek; Menno van der Eerden; Dennis Hesselink; Herold Metselaar; Annelies Verbon; Jurriaan de Steenwinkel; GI (Georgina) Aron; Eric van Gorp; Sander van Boheemen; Jolanda Kreeft - Voermans; Charles Boucher; Richard Molenkamp; Marion Koopmans; Corine Geurts van Kessel; Annemiek Baltissen - van der Eijk

doi:10.1038/s41467-020-20568-4

Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

Charles Boucher, Richard Molenkamp, Marion Koopmans, Corine Geurts van Kessel, Annemiek Baltissen - van der Eijk

^*Corresponding author for this work

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Abstract

Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5–11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4–17.2). Multivariate analyses identify viral loads above 7 log₁₀ RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.

Original language	English
Article number	267
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20568-4
Publication status	Published - 11 Jan 2021

Bibliographical note

Funding Information:
Role of the funding source. This work partially was funded through EU COVID-19 grant RECOVER 101003589. The study sponsors were involved neither in the study design, the collection, analysis and interpretation of the data, writing of the report, nor in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Publisher Copyright:
© 2021, The Author(s).

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van Kampen, J., van de Vijver, D., Fraaij, P., Haagmans, B., Lamers, M., Okba, N., van den Akker, J., Endeman, R., Gommers, D., Cornelissen, J., Hoek, R. A. S., van der Eerden, M., Hesselink, D., Metselaar, H., Verbon, A., de Steenwinkel, J., Aron, GI., van Gorp, E., van Boheemen, S., ... Baltissen - van der Eijk, A. (2021). Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nature Communications, 12(1), Article 267. https://doi.org/10.1038/s41467-020-20568-4

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title = "Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)",

abstract = "Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8\%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5{\textendash}11) and drops below 5\% after 15.2 days post onset of symptoms (95\% confidence interval (CI) 13.4{\textendash}17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.",

author = "\{van Kampen\}, Jeroen and \{van de Vijver\}, David and Pieter Fraaij and Bart Haagmans and Mart Lamers and Nisreen Okba and \{van den Akker\}, Johan and Rik Endeman and Diederik Gommers and Jan Cornelissen and R.A.S. Hoek and \{van der Eerden\}, Menno and Dennis Hesselink and Herold Metselaar and Annelies Verbon and \{de Steenwinkel\}, Jurriaan and Aron, \{GI (Georgina)\} and \{van Gorp\}, Eric and \{van Boheemen\}, Sander and \{Kreeft - Voermans\}, Jolanda and Charles Boucher and Richard Molenkamp and Marion Koopmans and \{Geurts van Kessel\}, Corine and \{Baltissen - van der Eijk\}, Annemiek",

note = "Funding Information: Role of the funding source. This work partially was funded through EU COVID-19 grant RECOVER 101003589. The study sponsors were involved neither in the study design, the collection, analysis and interpretation of the data, writing of the report, nor in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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van Kampen, J , van de Vijver, D , Fraaij, P , Haagmans, B, Lamers, M, Okba, N, van den Akker, J , Endeman, R , Gommers, D, Cornelissen, J, Hoek, RAS , van der Eerden, M , Hesselink, D , Metselaar, H , Verbon, A , de Steenwinkel, J, Aron, GI, van Gorp, E , van Boheemen, S , Kreeft - Voermans, J, Boucher, C, Molenkamp, R , Koopmans, M , Geurts van Kessel, C & Baltissen - van der Eijk, A 2021, 'Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)', Nature Communications, vol. 12, no. 1, 267. https://doi.org/10.1038/s41467-020-20568-4

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T1 - Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

AU - van Kampen, Jeroen

AU - van de Vijver, David

AU - Fraaij, Pieter

AU - Haagmans, Bart

AU - Lamers, Mart

AU - Okba, Nisreen

AU - van den Akker, Johan

AU - Endeman, Rik

AU - Gommers, Diederik

AU - Cornelissen, Jan

AU - Hoek, R.A.S.

AU - van der Eerden, Menno

AU - Hesselink, Dennis

AU - Metselaar, Herold

AU - Verbon, Annelies

AU - de Steenwinkel, Jurriaan

AU - Aron, GI (Georgina)

AU - van Gorp, Eric

AU - van Boheemen, Sander

AU - Kreeft - Voermans, Jolanda

AU - Boucher, Charles

AU - Molenkamp, Richard

AU - Koopmans, Marion

AU - Geurts van Kessel, Corine

AU - Baltissen - van der Eijk, Annemiek

N1 - Funding Information: Role of the funding source. This work partially was funded through EU COVID-19 grant RECOVER 101003589. The study sponsors were involved neither in the study design, the collection, analysis and interpretation of the data, writing of the report, nor in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: © 2021, The Author(s).

PY - 2021/1/11

Y1 - 2021/1/11

N2 - Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5–11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4–17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.

AB - Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients (17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5–11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4–17.2). Multivariate analyses identify viral loads above 7 log10 RNA copies/mL (odds ratio [OR] of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.

UR - https://www.scopus.com/pages/publications/85099202160

U2 - 10.1038/s41467-020-20568-4

DO - 10.1038/s41467-020-20568-4

M3 - Article

C2 - 33431879

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 267

ER -

Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19)

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