Cycle threshold SARS-CoV-2 RT-PCR and bronchoalveolar cytokine
concentrations redefine the COVID-19 phenotypes in critically ill
patients
Abstract
Abstract Rationale: Recent studies suggest that both hypo- and
hyper-inflammatory ARDS phenotypes characterize severe COVID-19-related
pneumonia. The role of lung SARS-CoV-2 viral load in contributing to
these phenotypes remains unknown. Objectives: To redefine COVID-19 ARDS
phenotypes when considering semi-quantitative SARS-CoV-2 RT-PCR in the
bronchoalveolar lavage of intubated patients. To compare the relevance
of deep respiratory samples vs plasma in linking the immune response and
the semi-quantitative viral loads. Methods: Eligible subjects were
adults diagnosed with COVID-19 ARDS who required mechanical ventilation
and underwent bronchoscopy. We recorded the immune response in the
bronchoalveolar lavage and plasma and semi-quantitative SARS-CoV-2
RT-PCR in the bronchoalveolar lavage. Hierarchical clustering on
principal components was applied separately on the two compartments
datasets. Baseline characteristics were compared between clusters.
Measurements and Results: 20 subjects were enrolled between August 2020
and March 2021. Subjects underwent bronchoscopy on average 3.6 days
after intubation. All subjects were treated with dexamethasone prior to
bronchoscopy, 11 of 20 (55.6%) received remdesivir and 1 of 20 (5%)
received tocilizumab. Adding viral load information to the classic two
cluster model of ARDS revealed a new cluster characterized by
hypo-inflammatory responses and high viral load in 23.1% of the cohort.
Hyperinflammatory ARDS was noted in 15.4% of subjects. Bronchoalveolar
lavage clusters were more stable compared to plasma. Conclusions: We
identified a unique group of critically ill subjects with COVID-19 ARDS
who exhibit hypo-inflammatory responses but high viral loads in the
lower airways. Our approach adds the infection dimension to ARDS
phenotypes described in COVID-19 pneumonia