Symptomatology of SARS-CoV-2 versus seasonal coronavirus infection in healthy young children

Background: Since SARS‑CoV‑2 became established in humans, children encounter it from early life, similar to seasonal human coronaviruses (hCoVs). To understand how SARS‑CoV‑2 compares to other hCoVs in early childhood, we measured infections and symptoms in an unvaccinated community cohort. Methods: The VIOOL study follows healthy children under 4 years for 16 weeks during three winter seasons (2021–2024). A total of 228 participants provided weekly nasal swabs, regardless of symptoms, tested for betacoronaviruses SARS‑CoV‑2 and OC43, and alphacoronaviruses NL63 and 229E. Daily symptoms were recorded. Regression models, adjusting for age, co‑infections, and repeated measures, were used to compare clinical presentation across viruses. Cox models evaluated whether prior homotypic or heterotypic infections influenced subsequent infection risk. Results: Across 3540 person‑weeks, we detected 78 infections with SARS‑CoV‑2, 149 with OC43, 39 with NL63, and seven with 229E (incidence 7.7/100 person‑weeks; 95% CI: 6.8–8.6). Acute Respiratory Illness occurred in similar proportions across viruses. Runny nose, coughing, wheezing, and fever were the most common symptoms, with no major differences in severity or episode length. Sequential infections were frequent (42%). Prior alphacoronavirus infection modestly reduced betacoronavirus infection risk. Conclusion: SARS-CoV-2 resembles other hCoVs in symptoms and severity. Cross-protection from heterotypic coronaviruses may depend on order of infections.