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

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.

Impact of Early Corticosteroids on 60-day Mortality in Critically Ill Patients with COVID-19: A Multicenter Cohort Study of the OUTCOMEREA Network

“…One of the potential consequences of immunosuppression is delayed SARS-CoV-2 RNA clearance [47], which had already been observed in SARS and MERS [6] but not observed in SARS-COV 2 patients [48]. In addition, the immunosuppression induced by steroids could also lead to a higher risk of superinfections [23,45].…”

Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort

“…In the case of SARS-CoV-2, several antiviral drugs have been tested, but the effects on viral kinetics or even symptom evolution remain modest, even though promising results were recently found with monoclonal antibodies ( 43 ). It is also possible that viral replication in the lower respiratory tract (LRT) is a better predictor of outcome than nasopharyngeal viral load ( 44 ). Here our data showed a correlation between viral load values in both compartments ( SI Appendix , Fig.…”

Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome

“…We may hypothesize that evolution of COVID-19 toward increasing severity in this population of old patients is mainly a consequence of this altered immune status [ 32 – 35 ]. For example, previous studies showed the negative correlation between lymphocytes count and pulmonary viral load [ 36 , 37 ] while, elsewhere, the magnitude of pulmonary viral load was repeatedly associated with increased mortality [ 8 , 38 – 43 ]. In the present work, this is also illustrated by the association between nasopharyngeal viral load and increased mortality, SOFA and IL-6 levels upon admission.…”

“…First, it probably participates in the long duration necessary to eradicate SARS-CoV-2 from the lung in invasively ventilated patients as described elsewhere [ 43 ]. For example, it was shown that the viral shedding in lower respiratory tract lasted almost 30 days in median in critically ill COVID-19 patients [ 38 , 42 ]. Second, it most likely contributes to the very high rates of nosocomial infections reported not only in the present study (50%) but also in many others [ 26 , 27 , 45 ].…”