Incidence and risk factors of acute respiratory illness associated with influenza, COVID-19, and respiratory syncytial virus within a birth cohort study

Influenza virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV) are leading causes of acute respiratory infections (ARIs). New Zealand's coronavirus disease 2019 (COVID-19) public health measures disrupted the circulation of these viruses in 2020-2021, creating a rare opportunity to explore the impact of potential immunity gaps on age-specific infection risk. We analyzed data from 843 participants aged between 0 and 4 years enrolled in the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance 3 (SHIVERS-III) birth cohort, a longitudinal community-based study in New Zealand, during 2020-2024. During the respiratory season, weekly surveillance captured ARI symptoms and severity. Nasal swabs were collected from symptomatic participants and tested for viral RNA by RT-PCR. Incidence rates (IRs) and incidence rate ratios (IRRs) were estimated for the surveillance period and adjusted for age, sex, ethnic group, socioeconomic status, and influenza vaccination status. No influenza or SARS-CoV-2 infections were detected in 2020 and 2021. From 2021 to 2024, RSV had the highest IR during the surveillance period (63.2/100 person-years [PY]; 95% CI, 56.6-69.8), followed by SARS-CoV-2 (39.3/100 PY; 95% CI, 34.5-44) and influenza (35.7/100 PY; 95% CI, 29-42.3). Age influenced infection risk: infants <6 months had the lowest incidence of influenza and RSV, potentially reflecting maternally derived immunity and limited exposure. Risk increased after 6 months of age, peaking at age 1 year for RSV and at age 2 years for influenza. Influenza vaccination lowered symptomatic influenza risk (IRR 0.66; 95% CI, 0.44-1.00). In the New Zealand community setting in the post-COVID-19 era, individual respiratory virus illness patterns differ in children aged 0-4. Influenza vaccine shows protection, and age influences virus-specific risk. IMPORTANCE: Influenza virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV) are major causes of acute respiratory illness in early childhood, yet current understanding is largely reliant on hospital-based surveillance that underestimates the broader community burden. This study addresses this limitation by providing comprehensive, community-based estimates of incidence, severity, and symptom profiles across these viruses within a single longitudinal birth cohort. By leveraging the unique epidemiological context created by pandemic-related disruptions, it offers important insights into how changes in exposure influence subsequent infection risk and virus circulation. The direct comparison of three major respiratory viruses within the same population highlights distinct age-related risk patterns and disease characteristics. In addition, our research provides real-world evidence of the reduced risk of influenza-associated acute respiratory illness among vaccinated children. These findings strengthen the evidence base for age-targeted immunization strategies and improve understanding of early-life respiratory virus epidemiology.