Dynamics of the alveolar host response and pulmonary infections in ARDS

This thesis explores alveolar host-immune responses, viral kinetics, and secondary pulmonary infections in acute respiratory distress syndrome (ARDS), with a focus on COVID-19-related ARDS. It investigates persistent inflammation, alveolar subphenotypes, fibroproliferation, and their impact on outcomes.
The thesis demonstrates that COVID-19 ARDS is characterized by a hyperinflammatory alveolar state with increased inflammatory biomarkers associated with higher mortality and distinct inflammatory profiles in the alveolar and systemic compartments. Two distinct alveolar inflammatory subphenotypes were identified, revealing poor agreement between alveolar and systemic subphenotypes. A fibroproliferative response, marked by increased NT-PCP-III, correlated with short-term outcomes but showed weak association with long-term lung function.
The thesis also examines viral dynamics, showing that alveolar SARS-CoV-2 viral loads decrease in a biphasic pattern, with high early viral loads associated with worse outcomes. Pulmonary viral reactivations, particularly HSV, were common in ARDS, and associated with increased inflammation and mortality. Antiviral treatment was found to reduce inflammation.
These findings emphasize the role of alveolar inflammation and viral reactivations in ARDS pathophysiology. They support the need for precision medicine strategies targeting these processes to improve patient outcomes. Future research should expand beyond COVID-19-related ARDS to include broader populations at risk for persistent inflammation and viral reactivation.