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

Jeroen J A van Kampen, David A M C van de Vijver, Pieter L A Fraaij, Bart L Haagmans, Mart M Lamers, Nisreen Okba, Johannes P C van den Akker, Henrik Endeman, Diederik A M P J Gommers, Jan J Cornelissen, Rogier A S Hoek, Menno M van der Eerden, Dennis A Hesselink, Herold J Metselaar, Annelies Verbon, Jurriaan E M de Steenwinkel, Georgina I Aron, Eric C M van Gorp, Sander van Boheemen, Jolanda C Voermans, Charles A B Boucher, Richard Molenkamp, Marion P G Koopmans, Corine Geurtsvankessel, Annemiek A van der Eijk, Jeroen J A van Kampen, David A M C van de Vijver, Pieter L A Fraaij, Bart L Haagmans, Mart M Lamers, Nisreen Okba, Johannes P C van den Akker, Henrik Endeman, Diederik A M P J Gommers, Jan J Cornelissen, Rogier A S Hoek, Menno M van der Eerden, Dennis A Hesselink, Herold J Metselaar, Annelies Verbon, Jurriaan E M de Steenwinkel, Georgina I Aron, Eric C M van Gorp, Sander van Boheemen, Jolanda C Voermans, Charles A B Boucher, Richard Molenkamp, Marion P G Koopmans, Corine Geurtsvankessel, Annemiek A van der Eijk

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Viral loads and duration of…
Fig. 1. Viral loads and duration of symptoms for infectious virus shedding.
Viral RNA loads (Log10 RNA copies/mL) in the respiratory samples versus the duration of symptoms (days). Black boxes represent virus culture positive samples and open red circles represent the virus culture negative samples.
Fig. 2. Probabilities of infectious virus shedding.
Fig. 2. Probabilities of infectious virus shedding.
Probit analyses of the detection of infectious virus in respiratory samples with cell culture for duration of symptoms in days (A) (n = 690 samples), viral RNA load in Log10 copies per mL (B) (n = 688 samples), and serum neutralizing antibody titer (C) (n = 112 samples). Blue line represent the probit curve and the dotted red lines represent the 95% confidence interval. Serum neutralizing antibody titers are expressed as plaque-reduction neutralization titers 50% as described previously.

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