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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. Although the role of intestinal microbiota in adults with SARS-CoV-2 infection has been studied, limited research exists on children. This study was performed to investigate the clinical significance and association of intestinal microbiota composition in children with SARS-CoV-2 infection during the 2021 and 2022 pandemic waves in Taiwan.METHODS: Pediatric patients diagnosed with SARS-CoV-2 via real-time reverse transcription polymerase chain reaction were randomly enrolled from Shang-Ho Hospital. The study period covered the two SARS-CoV-2 outbreaks in Taiwan in 2021 and 2022. Medical records were reviewed for clinical manifestations and cycle threshold (Ct) values, and fecal microbiota enrichment analysis was performed using next-generation sequencing and the linear discriminant analysis effect size method.RESULTS: In total, 21 pediatric patients with confirmed SARS-CoV-2 infection were enrolled-8 from the 2021 pandemic and 13 from the 2022 pandemic. Compared with the 2021 cohort, children infected in 2022 exhibited significantly higher rates of hospitalization (P < 0.001), high fever (>39 Â°C) (P = 0.0002), and dehydration (P = 0.0001). By contrast, a higher prevalence of a family history of COVID-19 was observed in the 2021 group (P = 0.018). Permutational multivariate analysis of group dispersions (β-dispersion analysis) revealed a trend toward increased β-diversity in the 2021 group (P = 0.06394), along with a higher relative abundance of the genera Peptoniphilus, Fusobacterium, and Morganella.CONCLUSION: Our study highlights differences in clinical presentations between the 2021 and 2022 SARS-CoV-2 pandemic waves and suggests an impact of infection on the gut microbiota in children, with marginally higher β-diversity observed in 2021. These findings provide a foundation for future research into the role of intestinal microbiota in pediatric SARS-CoV-2 infection.