Protracted viral shedding and viral load are associated with ICU mortality in Covid-19 patients with acute respiratory failure

Abstract

Background Protracted viral shedding is common in hospitalized patients with COVID-19 pneumonia, and up to 40% display signs of pulmonary fibrosis on computed tomography (CT) after hospital discharge. We hypothesized that COVID-19 patients with acute respiratory failure (ARF) who die in intensive care units (ICU) have a lower viral clearance in the respiratory tract than ICU patients discharged alive, and that protracted viral shedding in respiratory samples is associated with patterns of fibroproliferation on lung CT. We, therefore, conducted a retrospective observational study, in 2 ICU of Lyon university hospital. Results 129 patients were included in the study, of whom 44 (34%) died in ICU. 432 RT-PCR for SARS-CoV-2 were performed and 137 CT scans were analyzed. Viral load was significantly higher in patients deceased as compared to patients alive at ICU discharge (p < 0.001), after adjustment for the site of viral sampling and RT-PCR technique. The median time to SARS-CoV-2 negativation on RT-PCR was 19 days [CI95 %:15–21] in patients alive at ICU discharge and 26 days [CI95 %:17-infinity] in non-survivors at ICU discharge. Competitive risk regression identified patients who died in ICU and age as independent risk factors for longer time to SARS-CoV-2 negativation on RT-PCR, while antiviral treatment was independently associated with shorter time. None of the CT scores exploring fibroproliferation (i.e., bronchiectasis and reticulation scores) were significantly associated with time to SARS-CoV-2 negativation. Conclusions Viral load in respiratory samples is significantly lower and viral shedding significantly shorter in ICU survivors of COVID-19 associated acute respiratory failure. Protracted viral shedding is unrelated to occurrence of fibrosis on lung CT.

Relationships between Viral Load and the Clinical Course of COVID-19

“…The viral load may change the disease phase; this may be a reason for the differences [ 16 ]. Bitker et al suggested that sustained abrogation of type-I interferon production may be associated with longer viral shedding and disease severity [ 17 ]. However, it is unclear if these mechanisms result in a relationship between viral load and disease severity.…”

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.…”

“…In such critically ill patients with prolonged ICU stays, this immunosuppressed status presents with deleterious consequences. 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 ].…”

Lower respiratory tract and plasma SARS-CoV-2 RNA load in critically ill adult COVID-19 patients: Relationship with biomarkers of disease severity

“…Moreover, neither initial nor peak viral load in TA was associated with increased mortality (OR, 0.81; 95% CI, 0.68-2.24; P =0.68, and OR, 0.39; 95% CI, 0.22-1.82; P =0.39, respectively) (Supplementary Table 3). Other studies, in contrast, pointed to an association between protracted SARS-CoV-2 RNA clearance in LRT and/or simple presence of SARS-CoV-2 RNA in LRT and increased risk of mortality [7] , [8] , [9] . In these studies, a wide variety of LRT specimens were used, and no data proving a dose-dependent relationship between SARS-CoV-2 RNA load in LRT and mortality were provided.…”