Pediatric COVID-19 Reinfection Linked to Increased Risk of Long COVID

As SARS-CoV-2 continues to circulate, reinfections have become increasingly common. And while most pediatric COVID-19 cases remain mild, new evidence suggests that each subsequent infection may carry a greater risk of long-term complications.

A large retrospective study by Zhang et al. published in The Lancet Infectious Diseases found that children and adolescents who experienced a second documented COVID-19 infection were more than twice as likely to receive a clinical diagnosis of long COVID compared with those after a first infection. Drawing on electronic health records from 40 pediatric hospitals and health systems participating in the NIH RECOVER Initiative, investigators analyzed the records of 465,717 patients younger than 21 years with documented SARS-CoV-2 infection between January 2022 and October 2023. Of these, 58,417 pediatric and adolescent patients experienced a documented reinfection during the Omicron period.

After rigorous propensity-score matching to account for demographic characteristics, comorbidities, healthcare utilization, vaccination status, and illness severity, reinfection remained independently associated with a significantly higher risk of post-acute sequelae of SARS-CoV-2 infection (PASC).

Reinfection Increased Risk Across Multiple Organ Systems

The primary outcome, a clinician-documented diagnosis of long COVID, was more than twice as common following reinfection (relative risk [RR] 2.08; 95% CI, 1.68–2.59). Incidence rates nearly doubled, rising from approximately 904 cases to 1,884 cases per million children over six months.

Beyond the formal long COVID diagnosis, reinfection was associated with elevated risk across numerous clinical manifestations affecting multiple organ systems, including:

• Myocarditis (RR 3.60)
• Loss of taste or smell (RR 2.83)
• Thromboembolic complications (RR 2.28)
• Heart disease (RR 1.96)
• Acute kidney injury (RR 1.90)
• Fatigue and malaise (RR 1.50)
• Headache (RR 1.46)
• Musculoskeletal pain (RR 1.45)
• Abdominal pain (RR 1.42)
• Mental health conditions (RR 1.38)
• Cognitive impairment (RR 1.32)
• Respiratory symptoms (RR 1.29)

Importantly, the increased risk associated with reinfection persisted across both vaccinated and unvaccinated children, as well as among those with mild and severe acute infections. The subgroup analyses were designed to determine whether reinfection increased risk within each group, not to compare vaccination status or severity of acute infection directly.

What This Means for Clinical Practice

The study serves as a reminder that persistent symptoms following repeat COVID-19 infections warrant careful evaluation. Fatigue, headaches, chest pain, cognitive complaints, exercise intolerance, dysautonomia, and lingering respiratory symptoms may represent manifestations of pediatric long COVID rather than isolated post-viral complaints.

The study also supports ongoing preventive efforts. Although vaccination status did not completely eliminate reinfection-associated risk, reducing the likelihood of infection remains a key strategy for lowering the overall burden of PASC. The authors emphasize maintaining age-appropriate vaccination, identifying children at higher risk, and ensuring access to longitudinal follow-up for those with persistent symptoms.

The authors note several limitations. Home testing may have resulted in missed infections, some reinfections may have gone undocumented, and electronic health records cannot capture every symptom experienced outside the healthcare system.

Nevertheless, the study represents the largest pediatric EHR analysis of long COVID following reinfection to date and provides some of the strongest real-world evidence that repeated SARS-CoV-2 infections may contribute to cumulative long-term morbidity in children and adolescents.

Reference:

Zhang B, Wu Q, Jhaveri R, et al; on behalf of the RECOVER Consortium. Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): A retrospective cohort study. Lancet Infect Dis. 2026;26(2):127-138. Published February 2026. doi:10.1016/S1473-3099(25)00476-1.