Second COVID-19 Infection in Children Doubles Long COVID Risk, Study Finds

Children and adolescents who become infected for the second time with COVID-19 are more likely to develop Long COVID, according to research recently published in The Lancet Infectious Diseases.

Bingyu Zhang

“Many had hoped reinfections of COVID would be milder or carry less long-term risk, but we found increased risks for a broad range of conditions, challenging the assumptions many had that children bounce back quickly,” first author Bingyu Zhang, M.S., an Applied Mathematics & Computational Science Ph.D. student in the Penn Computing, Inference and Learning (PennCIL) lab, said in a news release.

Long COVID is a chronic condition that can include a wide range of symptoms that can last weeks or months, but some people with long COVID can have persistent health issues and can lead to serious complications, including diabetes, heart conditions, blood clots, and neurological conditions.

Researchers at the Perelman School of Medicine at the University of Pennsylvania conducted a retrospective analysis of data from about 407,000 patients across 40 pediatric hospitals. They included patients who were younger than 21 who had both a first infection and/or a second infection of COVID-19 after Jan 1, 2022. Researchers used data from longitudinal electronic health records (EHRs) of hospitals participating in the NIH-funded Researching COVID to Enhance Recovery (RECOVER) Initiative. Funded by the National Institutes of Health, RECOVER data includes laboratory testing, vaccinations, clinical diagnoses, and healthcare encounters.

The researchers also examined the specific risk that a second infection posed for a variety of known conditions associated with Long COVID by examining health records dating to the omicron wave. The records were studied for a documented diagnosis of Long COVID, and then the researchers analyzed the records for updates covering a period of roughly one to six months after.

The analysis showed that among patients with just one documented COVID-19 infection, there was a population-level rate of 904 cases of Long COVID per million people every six months. But for those who experienced a second COVID-19 infection, the rate more than doubled to 1,884 cases per million.

Researchers found that pediatric patients who had COVID-19 twice were more than 3.5 times as likely to develop myocarditis, a swelling of heart muscle that can weaken the heart and be life-threatening, and doubled their chance of developing blood clots.

They also found that a second infection increased the risk of acute kidney injury, fluid and electrolyte disturbance, generalized pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, cognitive impairment, skin conditions, fever and chills, and respiratory signs and symptoms.

“To our knowledge, this study is the first and largest electronic health record (EHR)-based cohort to comprehensively evaluate the risk of PASC [Post-acute sequelae of SARS-CoV-2] after SARS-CoV-2 reinfection with the omicron variant (B.1.1.529) among children and adolescents,” the authors wrote. “These results suggest that reinfections might contribute to cumulative morbidity. Ongoing long-term follow-up is essential for informing clinical care and public health strategies to mitigate the pediatric burden of long COVID.”

Jeffrey Morris, Ph.D.

Researchers said they plan to track data on pediatric patients that span longer periods of time, examine whether newer COVID-19 variants change the risk patterns, and explore specific strategies that might help prevent severe long-term effects. They also hope to identify which categories of patients might be most vulnerable to long COVID and its associated conditions so families and clinicians can better protect them from the lasting impact of reinfections.

“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,” said co-author Jeffrey Morris, Ph.D., director of Biostatistics at the Perelman School of Medicine at the University of Pennsylvania.