COVID-19 Reinfection Heightens Risk of Postacute Sequelae of SARS-CoV-2 in Pediatrics

Data from a retrospective cohort study published in The Lancet Infectious Diseases demonstrates a markedly higher risk of various outcomes related to postacute sequelae of SARS-CoV-2 (PASC) in children and adolescents after reinfection with the virus. The results highlight the need for heightened vaccination efforts in younger populations.¹

Why Should Pediatric Long COVID be Investigated Further?

The COVID-19 pandemic brought with it a new wave of infectious disease phenomena. Most prominent among them is the incidence of PASC, or long COVID, in individuals infected with COVID-19. These patients experience myriad symptoms following their original infection for prolonged periods. These can span across cardiovascular, digestive, and cognitive systems, causing a constellation of poor outcomes.²

Research on long COVID in pediatric populations has been burdened by a lack of funding and recognition in the health care community. What is known is that the clinical features of long COVID differ between adults and children. Compared with adults, children and adolescents present more heterogeneous symptoms, like fatigue, dizziness, and mood changes. Because their manifestations of long COVID can be non-specific, determining factors that may influence the risk of long COVID development in younger patients is critical.^2,3

“Studying the public health consequences of COVID, including long COVID, helps us identify what children may be more vulnerable to after infection and direct support to them, such as allocating public health resources to monitor and manage long-term effects,” Jeffrey Morris, PhD, director of Biostatistics at University of Pennsylvania Perelman School of Medicine, said in a news release accompanying the results.⁴

What Can Reinfection Tell Us About Long COVID Risk?

Reinfection with SARS-CoV-2 is one such factor deserving further investigation, especially given the vast rates of reinfection with the virus across the pandemic period. The current investigators utilized data from institutions participating in the Researching COVID to Enhance Recovery (RECOVER) initiative to examine whether SARS-CoV-2 reinfection could increase the risk of long COVID outcomes. Over 400,000 patients aged under 21 years across 40 children’s hospitals and health institutions in the United States were included.¹

Across multiple outcomes, there was a significantly higher risk of PASC in patients with second infection episodes than in those with first infection episodes. COVID-19 reinfection was associated with a significantly increased risk of overall PASC diagnosis (U09.9; risk ratio [RR]: 2.08 [95% CI, 1.68—2.59]). More specifically, myocarditis, changes in taste and smell, heart disease, generalized pain, fatigue and malaise, and cognitive impairment were some of many potential PASC-related symptoms and conditions that showed increased risks, according to the investigators.¹

Increased PASC risk persisted across subgroups defined by COVID-19 vaccination status and acute phase severity. The authors noted that this indicates a heightened PASC risk with reinfection regardless of those factors.¹

Age-stratified analyses within each subgroup were employed to better elucidate the impacts of a second infection on PASC risk. The results demonstrated higher RRs of PASC diagnosis following reinfection among adolescents aged 12 through 20 years and children 5 through 11 years. Children aged 0 to 4 years had higher RRs of thrombophlebitis, thromboembolism, and abnormal liver enzymes. Notably, there were consistently elevated RRs for PASC outcomes after reinfection in both males and females.¹

What Do These Findings Mean for Public Health?

Reinfection has been a hallmark of the COVID-19 pandemic. Now, the current investigators have revealed that repeated infections can worsen long COVID outcomes, aligning with adult studies. If public health professionals know that reinfection can be a factor contributing to long COVID, there can be a greater emphasis on preventive measures such as vaccination. Parents and guardians who feel vaccination is the best choice for their child should be sure to discuss with their pharmacist the merits of protection.^1,4

It is paramount for research in this sector to continue. Yong Chen, PhD, a senior author of the study, noted that it could not have been completed without the “massive infrastructure and sustained support” provided by the RECOVER initiative and participating institutions. Pediatric populations have been studied less often than adults in long COVID, and to improve their outcomes, future investigations must span longer time periods and explore novel prevention strategies.^2,4

“The results of this study further support one of the strongest reasons I give patients, families and physicians about getting vaccinated: More vaccines should lead to fewer infections, which should lead to less long COVID,” Ravi Jhaveri, MD, study co-author and head of pediatric infectious diseases at Ann & Robert H. Lurie Children’s Hospital of Chicago, said in the news release.⁴

REFERENCES

1. Zhang B, Wu Q, Jhaveri R, et al. Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study. The Lancet Infect Dis. Online first: September 30, 2025. Accessed November 3, 2025. doi:10.1016/S1473-3099(25)00476-1

2. Halpern L. In the fragmented landscape of long COVID care, pharmacists are essential. Pharmacy Times. Published October 20, 2025. Accessed. November 3, 2025. https://www.pharmacytimes.com/view/in-the-fragmented-landscape-of-long-covid-care-pharmacists-are-essential

3. Rao S, Lee GM, Razzaghi H, et al. Clinical features and burden of postacute sequelae of SARS-CoV-2 infection in children and adolescents. JAMA Pediatr. 2022;176(10):1000-1009. doi:10.1001/jamapediatrics.2022.2800

4. University of Pennsylvania School of Medicine. Second infection in kids doubles long COVID risk. News Release. EurekAlert! Released October 1, 2025. Accessed November 3, 2025. https://www.eurekalert.org/news-releases/1100519