Failing Categorization of Severe Covid-19 Ards into Ventilatory Subphenotypes Studied Via the Clinical-Histopathologic Relationship

Background: Categorization of severe COVID-19 related acute respiratory distress syndrome (CARDS) into subphenotypes with different respiratory system compliance does not consider the trajectories of respiratory mechanoelastic features and overlapping histopathologic patterns. This study aimed to assess the mechanoelastic-histopathologic relationship in severe CARDS.Methods: Histopathologic analysis was performed on seventy-five consecutive full autopsies of critically ill patients who died from COVID-19. Daily mechanical ventilatory parameters were considered until day 30. Patients were categorized in two groups according to the median worst Crs during ICU stay (CrsICU).Results: Forty-one patients had complete daily ventilatory measures. An inverse correlation was found between the CrsICU and late-proliferative diffuse alveolar damage (DAD) (r=-0.381, p=0.026). Late proliferative DAD was more extensive (p=0.042), length of stay in ICU (p=0.004) and duration of mechanical ventilation were longer (p=0.004) in the “low” than in the “high” CrsICU group. Cluster analysis further endorsed these findings.Conclusions: In critically ill patients who died from severe CARDS, respiratory compliance worsened during prolonged mechanical ventilation and was consistent with fibroproliferative evolution from early damage. Categorization of CARDS into ventilatory subphenotypes by mechanoelastic properties at ICU admission does not account for the complexity of the histopathologic features.