SARS-CoV-2 reinfection ups paediatric long COVID risk

Findings from the retrospective RECOVER-EHR* study show an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, in children and adolescents after a SARS-CoV-2 reinfection.

“[W]e observed an increased risk of PASC across multiple organ systems after a SARS-CoV-2 reinfection, reinforcing concerns about the long-term consequences of reinfection,” said the researchers.

Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (relative risk [RR], 2.08). [Lancet Infect Dis 2025;doi:10.1016/S1473-3099(25)00476-1]

There was also an increased risk of a variety of potential postacute symptoms and conditions, including myocarditis (RR, 3.60), taste and smell alterations (RR, 2.83), thrombophlebitis and thromboembolism (RR, 2.28), heart disease (RR, 1.96), acute kidney injury (RR, 1.90), fluid and electrolyte disturbance (RR, 1.89), generalized pain (RR, 1.70), arrhythmias (RR, 1.59), abnormal liver enzymes (RR, 1.56), chest pain (RR, 1.53), and fatigue and malaise (RR, 1.50).

Other conditions were headache (RR, 1.46), musculoskeletal pain (RR, 1.45), abdominal pain (RR, 1.42), mental ill health (RR, 1.38), postural orthostatic tachycardia syndrome (POTS) or dysautonomia (RR, 1.35), cognitive impairment (RR, 1.32), skin conditions (RR, 1.29), fever and chills (RR, 1.29), respiratory signs and symptoms (RR, 1.29), myositis (RR, 1.21), and cardiovascular signs and symptoms (RR, 1.15).

“These findings emphasize the ongoing risk of PASC with reinfection, regardless of severity, and suggest that the risk of PASC might be cumulative with each successive infection,” the investigators noted.

Despite stable T-cell responses, neutralizing antibody concentrations wane over time, which may compromise immunity upon reinfection. [BMJ Med 2023;2:e000468] Protection against natural infection also diminished more rapidly during the Omicron era, with reinfections becoming more common, especially in younger adults (aged 18–49 years). [Nature 2025;639:1024-1031; MMWR Morb Mortal Wkly Rep 2023;72:683-689]

“These dynamics elevate the need to understand reinfection risks in children, a group increasingly affected yet understudied in this context,” they explained.

Still a global concern

“[PASC] has emerged as a pronounced global concern with substantial long-term health effects in adults and children … Understanding how PASC manifests in children is crucial for improving diagnosis, treatment, and long-term monitoring,” said the researchers. “The growing frequency of SARS-CoV-2 reinfections in the Omicron era underscores the need to understand their long-term consequences.”

The team evaluated the risk of PASC diagnosis and symptoms and conditions potentially related to PASC in 465,717 children and adolescents (mean age 8.17 years, 50.2 percent male) after a SARS-CoV-2 reinfection during the Omicron period. A total of 407,300 participants had a first infection, while 58,417 had a second infection from January 1, 2022 to October 13, 2023.

The incidence rate of PASC diagnosis per million people per 6 months was 903.7 in the first infection group and 1,883.7 in the second infection group.

The investigators cited numerous studies on paediatric cohorts linking PASC to POTS, exercise intolerance, vascular problems, and CNS issues. [Eur J Pediatr 2024;183:2375-2382; Pediatr Infect Dis J 2024;43:795-802; Pediatr Pulmonol 2023;58:2059-2067; Front Pediatr 2023;11:1165072] “Our real-world data add to this literature by showing that postacute sequelae persist across reinfections and continue to impose a measurable clinical burden.”

Evidence shows that immunization can reduce the risk of PASC by preventing infections. [EClinicalMedicine 2024;79:102962] The results underscore the need to promote vaccination in younger cohorts and support ongoing investigations to better understand PASC, identify high-risk patient subgroups, and improve prevention and care strategies, the researchers added.

“Strengthening public health messaging and expanding vaccination access might help reduce the burden of PASC in children … Ongoing long-term follow-up is essential for informing clinical care and public health strategies to mitigate the paediatric burden of long COVID,” they said.