Functional impairment in daily activities during the acute phase of COVID-19 and influenza among Japanese healthcare workers in the 2024/2025 season

While most comparative studies on the severity of COVID-19 and influenza have focused on hospitalization and mortality, the disease burden in populations not requiring hospitalization remains poorly characterized. We aimed to compare the acute disease burden of influenza versus COVID-19 using functional impairment in daily activities among healthcare workers during the 2024/2025 season. A prospective cohort was established with a serosurvey in December 2024 and follow-up in March 2025. Severity was assessed by functional impairment in daily activities. Stabilized inverse probability weighting and multinomial logistic regression estimated relative risk ratios (RRRs) for influenza versus COVID-19. Pre-infection antibody associations with severity were also examined. Among 1,454 participants, 50 developed COVID-19 and 84 developed influenza. Compared with COVID-19, influenza showed higher RRRs for moderate (1.72; 95% CI, 0.63–4.64), severe (3.50; 1.15–10.7), and prolonged ≥ 5-day functional impairment (3.40; 0.87–13.4), although the CIs were wide. These associations were attenuated after adjustment for prior infection during the pandemic. Higher pre-infection SARS-CoV-2 nucleocapsid antibody levels were associated with lower severity among COVID-19 cases. In the 2024/2025 season, influenza was associated with more severe and longer-lasting functional impairment than COVID-19 among relatively healthy healthcare workers, possibly reflecting differential natural infection opportunities during the pandemic.