First and second wave among hospitalized COVID-19 patients with severe pneumonia: a comparison of 28-day mortality over 1-year pandemic in a tertiary university hospital in Italy.

Objectives: The first COVID-19-19 epidemic wave was over the period February-May 2020. Since October 1st, 2020 Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients. Design: Observational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of hazard ratios (HRs) with 95% confidence intervals (CI). A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed. Setting: University Hospital of Modena, Italy. Patients admitted to hospital for severe COVID-19 pneumonia during the first (February 22nd – May 31st, 2020) and second wave (October 1st- December 31st, 2020) were included. Results: During the two study periods, a total of 1,472 patients with severe COVID-19 pneumonia were admitted to our hospital, 449 during the first wave and 1,023 during the second. Median age was 70 years (IQR:56-80), 37% females, 49% with PaO /FiO < 250 mmHg, 82% with ≥1 comorbidity, median duration of symptoms was 6 days. 28-day mortality rate was 20.0% (95% CI:16.3-23.7) during the first wave vs. 14.2% (95% CI:12.0-16.3) in the second (log-rank test p-value= 0.03). After including key predictors of death in the multivariable Cox regression model, the data still strongly suggested a lower 28-day mortality rate in the 2nd wave (aHR=0.64, 95% CI: 0.45, 0.90, p- value=0.01). Conclusions: In our hospitalized COVID-19 patients with severe pneumonia, the 28-day mortality appeared to be reduced by 36% during the second as compared to the first wave. Further studies are needed to identify factors that may have contributed to this improved survival.