SARS-CoV-2 detection in the lower respiratory tract of invasively ventilated ARDS patients

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SARS-CoV-2 detection in the lower respiratory tract of invasively ventilated ARDS patients Niccolò Buetti1,2,3*† , Paul-Henri Wicky4†, Quentin Le Hingrat1,5, Stéphane Ruckly1, Timothy Mazzuchelli2, Ambre Loiodice1, Pierpaolo Trimboli6,7, Valentina Forni Ogna2, Etienne de Montmollin1,4, Enos Bernasconi8, Benoit Visseaux1,5 and Jean-François Timsit1,4

Abstract Background: Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. Methods: We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms’ onset and date of sampling. Results: From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13–12.64, p = 0.03). Conclusions: The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality. Keywords: SARS-CoV-2, COVID-19, Viral shedding, Viral load, Lower respiratory tract, ICU, Mortality

Background The SARS-CoV-2 disseminated in Europe in late February 2020, causing the largest pandemic due to any respiratory viruses any respiratory viruses in recent history [1]. Several authors suggested that viral shedding and severity of disease might be correlated [2], but they mostly focused on viral presence in upper respiratory secretions * Correspondence: [email protected] † Niccolò Buetti and Paul-Henri Wicky contributed equally to this work. 1 University of Paris, INSERM, IAME, F-75006 Paris, France 2 Ente Ospedaliero Cantonale, Locarno Community Hospital, Locarno, Switzerland Full list of author information is available at the end of the article

[3, 4]. Viral shedding from upper respiratory tract appeared to be higher soon after symptoms’ onset, but during the course of disease, the shedding originates predominantly from the lower respiratory tract (LRT) [5]. To date, data on viral replication in distal airways are scarce. Only one small study partly investigated the role of viral presence into LRT [6]. Moreover, the association between SARS-CoV-2 viral load in LRT and mortality remains unevaluated [7]. Our obje