Smilow Research Building on Feb. 3, 2024.
Credit: Zenna Haroon
Penn Medicine researchers found that children and adolescents who contract COVID-19 for a second time are twice as likely to develop long COVID compared to those who are infected only once, according to a new study.
The findings, published in The Lancet Infectious Diseases journal, also link repeat infections to elevated risks of heart disease, kidney damage, cognitive impairment, and other conditions. The researchers used data drawn from the RECOVER electronic health record database, which standardizes information across sites and undergoes rigorous quality assessments.
In total, the study included 465,717 subjects, making it one of the largest studies — with extended follow-up — of pediatric long COVID to date. The study design compared first versus second infections during a certain period of time, aligning calendar time and time from infection to isolate reinfection-specific risk.
Researchers also conducted extensive sensitivity analyses, including negative control experiments, subgroup analyses by age and sex, and adjustments for potential confounders.
Analyzing data from roughly 407,000 pediatric patients across 40 United States children’s hospitals, the researchers report that among those with a single COVID-19 infection, about 904 cases of long COVID per million emerge within six months. For those with a documented second infection, that rate doubled to 1,884 per million.
The Penn Medicine news release reports that repeat infection was also associated with a higher incidence of cardiovascular, renal, and neurologic conditions. For example, myocarditis risk more than tripled after a second infection, and blood clots became more than twice as likely.
Additional risks included increased incidence of kidney complications, cognitive issues such as memory and concentration problems, and vascular conditions.
The study fits with broader concerns about pediatric long COVID. According to previous discourse, long COVID in children causes myriad respiratory, cardiovascular, neurological, and psychological symptoms and remains understudied due to heterogeneity in definitions and follow-up durations. While most pediatric COVID-19 cases are mild in terms of acute infection, some persist with symptoms spanning months.
The study also discusses pediatric reinfection risk in the context of weakened strength of the immune system. During the omicron era, antibody protection declines over time even as T-cell responses remain stable, and protection from natural infection “diminished more rapidly.”
The researchers note that reinfections may contribute to cumulative morbidity in children and adolescents, highlighting the importance of ongoing follow-up medical care to inform clinical care for other patients and public health strategies more generally. They also stated that low vaccination rates in younger populations increase vulnerability since immunization remains one of the only tools shown to reduce long COVID risk by preventing reinfection.
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