CRITICALLY ILL PATIENTS WITH COVID-19 PNEUMONIA: PATHOPHYSIOLOGY, IMPACT OF VACCINE, AND CLINICAL OUTCOME.

The coronavirus disease 2019 (COVID-19) was diagnosed in late December 2019 in China and then quickly worldwide evolved in a pandemic. The clinical spectrum of the disease ranges from asymptomatic conditions to the development of acute respiratory distress syndrome (ARDS) with need of intensive care unit (ICU) admission. The present manuscript focuses on three main topics. The first part is a physiologic study designed to investigate the effects of inspired oxygen fraction (FiO2) and positive end-expiratory pressure (PEEP) on gas exchange in mechanically ventilated patients with ARDS due to COVID-19. Two FiO2 (100% and 40%) were tested at 3 decreasing levels of PEEP (15, 10, and 5 cmH2O). In the fourteen enrolled patients, PEEP of 15 cmH2O, despite resulting in the highest oxygenation, was associated with overdistension while PEEP of 5 cmH2O was associated with increased shunt and alveolar collapse. Administration of 100% FiO2 was associated with an increase in intrapulmonary shunt in the setting of high PEEP. The second part is a multicentric study evaluating the daily values and the trends of clinical parameters during the ICU stay and analyzing their association with outcome in critically ill patients with COVID-19 admitted to 24 Italian ICUs. In 1260 patients we showed that both the daily values and the trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil-lymphocyte ratio, and platelets were associated with survival. For lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with the patient outcome. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with the patient outcome compared to the daily values. Finally, the third part of the manuscript is a multicentric study to determine the role of vaccination in preventing ICU admission for COVID-19 pneumonia through evaluation of Incidence Rate Ratio (IRR), and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to ICU. Both mRNA (BNT162b2 or mRNA-1273) and adenoviral vaccines (ChAdOx1 or Ad26.COV2.S) resulted associated with significant lower risk of ICU admission. Despite unvaccinated patients admitted to ICU were younger than vaccinated patients, had fewer comorbidities and a lower prevalence of immunosuppressive therapy, ICU mortality was not associated with vaccinated status.