Temporal Association Between Viral Infections and Intussusception: Comparing SARS-CoV-2 and Adenovirus Using Self-Controlled and Case-Control Designs

Objective To investigate the short-term risk of intussusception following SARS-CoV-2 and adenovirus infections in children Study design Using Japan's health insurance claims database from January 2015 to December 2022, a self-controlled risk interval (SCRI) design and a nested case-control (NCC) analysis with conditional logistic regression were employed to adjust for individual confounders and assess the robustness of the findings. Results The study included 3.6 million children aged <10 years, with 1,069 intussusception events identified by procedure codes. The SCRI analysis revealed a 4-fold increased incidence of intussusception within 0-1 months of SARS-CoV-2 infection (IRR 4.27, 95% CI 2.11-8.67) and a 6-fold increased incidence for adenovirus infection (IRR 6.09, 95% CI 3.18-11.66). The NCC analysis yielded consistent results, with odds ratios of 4.43 (95% CI 2.94-6.66) for SARS-CoV-2 and 8.21 (95% CI 6.12-11.02) for adenovirus. Monte Carlo resampling confirmed the stability of the estimates. Negative control windows showed no increased risk, supporting the validity of the observed associations. Conclusions This study provides population-scale evidence that both SARS-CoV-2 and adenovirus infections are associated with the risk of pediatric intussusception, with adenovirus demonstrating a stronger effect. The findings have implications for clinical vigilance and understanding the impact of viral infections on gastrointestinal disorders in children.