Identifying high-risk patients, particularly in intensive care units (ICUs), enhances treatment and reduces severe outcomes. Since the pandemic, numerous studies have examined COVID-19 patient profiles and factors linked to increased mortality. Despite six pandemic waves, to the best of our knowledge, there is no extensive comparative analysis of patients' characteristics across these waves in Portugal. Thus, we aimed to analyze the demographic and clinical features of 1041 COVID-19 patients admitted to an ICU and their relationship with the different SARS-Cov-2 variants in Portugal. Additionally, we conducted an in-depth examination of factors contributing to early and late mortality by analyzing clinical data and laboratory results from the first 72h of ICU admission. Our findings revealed a notable decline in ICU admissions due to COVID-19, with the highest mortality rates observed during the second and third waves. Furthermore, immunization could have significantly contributed to the reduction in the median age of ICU-admitted patients and the severity of their conditions. The factors contributing to early and late mortality differed. Age, wave number, D-dimers, and procalcitonin were independently associated with the risk of early death. As a measure of discriminative power for the derived multivariable model, an AUC of 0.825 (p < 0.001; 95% CI, 0.719-0.931) was obtained. For late mortality, amodel incorporating age, wave number, hematologic cancer, C-reactive protein, lactate dehydrogenase, and platelet counts resulted in an AUC of 0.795 (p < 0.001; 95% CI, 0.759-0.831). These findings underscore the importance of conducting comprehensive analyses across pandemic waves to better understand the dynamics of COVID-19.
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