Omicron Reinfections in Children Linked to Increased Risk of Long COVID: Study

This retrospective cohort study used data from the RECOVER consortium, consisting of medical records from 40 children's hospitals and health centers in the U.S. The study duration was January 2022 to October 2023, a period when the Omicron variant was prevalent.

The participants were children and adolescents aged less than 21 years (mean age: 8.17 years, 52% male). For a child to be defined as having a reinfection, they had to have tested positive for SARS-CoV-2 by PCR or antigen tests at least 60 days after a previous infection.

Researchers thereafter contrasted health outcomes after first and second infection.

Two methods were utilized to identify PASC:

• ICD-10-CM diagnosis code U09.9 (clinical diagnosis of long COVID).

• A definition of 24 physician-identified symptoms and conditions related to PASC was used.

Absolute risks were estimated, and relative risks (RRs) were computed using a modified Poisson regression model, which controlled for demographic, clinical, and healthcare utilization factors via exact matching and propensity score matching.

Key Findings: Elevated Risk of PASC Following Reinfection

The research found that SARS-CoV-2 reinfection greatly elevates the risk of PASC. A subsequent infection was compared to the initial infection and was found to be associated with:

•2.08-fold increased risk of a composite diagnosis of PASC (RR: 2.08; 95% CI, 1.68-2.59).

• 3.6-fold increased risk of myocarditis (RR: 3.60; 95% CI, 1.46-8.86).

• 2.83-fold increased risk of taste and smell abnormalities (RR: 2.83; 95% CI, 1.41-5.67).

• 2.28-fold increased risk of thromboembolism and thrombophlebitis (RR: 2.28; 95% CI, 1.71-3.04).

• 1.96-fold increased risk of heart disease (RR: 1.96; 95% CI, 1.69-2.28).

• 1.9-fold increased risk of acute kidney injury (RR: 1.90; 95% CI, 1.38-2.61).

• 1.89-fold increased risk of fluid and electrolyte disorders (RR: 1.89; 95% CI, 1.62-2.20).

• 1.70-fold increased risk of generalized pain (RR: 1.70; 95% CI, 1.48-1.95).

• 1.59-fold increased risk of arrhythmias (RR: 1.59; 95% CI, 1.45-1.74).

• 1.56-fold increased risk of abnormal liver enzymes (RR: 1.56; 95% CI, 1.24-1.96).

• 1.50-fold increased risk of fatigue and malaise (RR: 1.50; 95% CI, 1.38-1.64).

• 1.45-fold increased risk of musculoskeletal pain (RR: 1.45; 95% CI, 1.37-1.54).

• 1.42-fold increased risk of abdominal pain (RR: 1.42; 95% CI, 1.34-1.50).

• 1.35 times increased risk of postural orthostatic tachycardia syndrome (POTS) / dysautonomia (RR: 1.35; 95% CI, 1.20-1.51).

• 1.32 times increased risk of cognitive dysfunction (RR: 1.32; 95% CI, 1.15-1.50).

• 1.29 times increased risk of respiratory symptoms (RR: 1.29; 95% CI, 1.25-1.33).

This large cohort study reaffirms that reinfection with SARS-CoV-2 during the Omicron era considerably raises the risk of long COVID (PASC) in children and adolescents. As long COVID remains a significant public health concern, preventing children from being infected again is a key priority to minimize long-term health outcomes.

Reference:

Zhang, B., Wu, Q., Jhaveri, R., Zhou, T., Becich, M. J., Bisyuk, Y., Blancero, F., Chrischilles, E. A., Chuang, C. H., Cowell, L. G., Fort, D., Horowitz, C. R., Kim, S., Ladino, N., Liebovitz, D. M., Liu, M., Mosa, A. S. M., Schwenk, H. T., Suresh, S., … Chen, Y. (2025). Reinfection with SARS-CoV-2 in the Omicron era is associated with increased risk of Post-acute sequelae of SARS-CoV-2 infection: A RECOVER-EHR cohort study. In medRxiv.https://doi.org/10.1101/2025.03.28.25324858