Evolving SARS-CoV-2 virulence among hospital and university affiliates in Spain and Greater Boston

Background The COVID-19 pandemic caused by the SARS-CoV-2 virus greatly affected healthcare workers and healthcare systems. It also challenged schools and universities worldwide negatively affecting in-person education. We conducted this study is to assess the evolution of SARs-CoV-2 virulence over the course of the pandemic. Methods A combined cohort of affiliates from the University of Navarra, two hospitals in Spain, and one healthcare system in the Greater Boston area was followed prospectively from March 8 th , 2020, to January 31 st , 2022 for diagnosis with COVID-19 by PCR testing and related sequelae. Follow-up time was divided into four periods according to distinct waves of infection during the pandemic. Severity of COVID-19 was measured by case-hospitalization rate. Descriptive statistics and multivariable-adjusted statistics using the Poisson mixed-effects regression model were applied. Results For the last two periods of the study (January 1 st to December 15 th , 2021 and December 16 th , 2021 to January 31 st , 2022) and relative to the first period (March 8 th to May 31 st , 2020), the incidence rate ratios (IRRs) of hospitalization were 0.08 (95% CI, 0.03-0.17) and 0.03 (95% CI, 0.01-0.15), respectively. Interpretation The virulence of COVID-19 and immunity of our populations evolved over time, resulting in a decrease in case severity. We found the case-hospitalization rate decreased more than 90% in our cohort despite an increase in incidence.