Critical COVID-19 patients through first, second, and third wave: retrospective observational study comparing outcomes in intensive care unit

Background: The time-course of the coronavirus disease 2019 (COVID-19) pandemic was characterized by subsequent waves identified by peaks of intensive care unit (ICU) admission rates. During these periods, progressive knowledge of the disease led to the development of specific therapeutic strategies. This retrospective study investigates whether this led to improvement in outcomes of COVID-19 patients admitted to ICU. Methods: Outcomes were evaluated in consecutive adult COVID-19 patients admitted to our ICU, divided into three waves based on the admission period: the first wave from February 25th, 2020, to July 6th, 2020; the second wave from September 20th, 2020, to February 13th, 2021; the third wave from February 14th, 2021 to April 30th, 2021. Differences were assessed comparing outcomes and by using different multivariable Cox models adjusted for variables related to outcome. Further sensitivity analysis was performed in patients undergoing invasive mechanical ventilation (IMV). Results: Overall, 428 patients were included in the analysis: 102, 169, and 157 patients in the first, second, and third wave. The ICU and in-hospital crude mortalities were lower by 7% and 10% in the third wave compared to the other two waves (P>0.05). A higher number of ICU- and hospital-free days at day 90 was found in the third wave when compared to the other two waves (P=0.001). Overall, 62.6% underwent invasive ventilation, with decreasing requirement during the waves (P=0.002). The adjusted Cox model showed no difference in the hazard ratio (HR) for mortality among the waves. In the propensity-matched analysis the hospital mortality rate was reduced by 11% in the third wave (P=0.044). Conclusions: With application of best practice as known by the time of the first three waves of the pandemic, our study failed to identify a significant improvement in mortality rate when comparing the different waves of the COVID-19 pandemic, notwithstanding, the sub-analyses showed a trend in mortality reduction in the third wave. Rather, our study identified a possible positive effect of dexamethasone on mortality rate reduction and the increased risk of death related to bacterial infections in the three waves.