The COVID-19 pandemic has particularly affected older adults who are frail and have multiple chronic conditions. This study retrospectively analyzed the differences in clinical presentation and outcomes among patients admitted to a COVID-19 referral hospital at different stages of the outbreak, emphasizing age, multimorbidity, and functional impairment. Data from 1,264 patients hospitalized between February and June 2020 with radiological and clinical features indicative of COVID-19 pneumonia were reviewed, including demographics, laboratory results, clinical parameters, and outcomes. Patients were categorized based on the admission period (early phase: ascending pandemic wave; later phase: plateau and descending wave), age, initial RT-PCR results for SARS-CoV-2, presence of two or more chronic illnesses, and functional disability. Logistic regression with forward selection identified factors independently linked to in-hospital death. Findings showed that individuals admitted during the later phase were older, more often female, had greater multimorbidity, and were more likely to be functionally dependent. Paradoxically, these patients had less severe respiratory compromise at admission (PaO2/FiO2 268, IQR 174–361 vs. 238, IQR 126–327 mmHg, p < 0.001) and lower mortality (22% vs. 27%, p < 0.001). Age, compromised respiratory function, positive RT-PCR, higher number of chronic diseases (OR 1.166, 95% CI 1.036–1.313, p = 0.011), and functional disability (OR 1.927, 95% CI 1.027–3.618, p = 0.022) were associated with increased mortality, whereas admission during the later phase was linked to reduced risk (OR 0.427, 95% CI 0.260–0.700, p = 0.001). In conclusion, the timing of hospitalization and the COVID-19 clinical phenotype strongly influenced outcomes, beyond age, multimorbidity, and disability.
