- [NO DATA ON WHETHER ANY CHILDREN IN STUDY WERE VACCINATED.]
- Risk for developing long COVID doubled in kids who got infected with SARS-CoV-2 a second time.
- Reinfection's greater risk also held up in a range of potential long COVID-related conditions and symptoms.
- Researchers said that finding a cure for long COVID needs to become a top research and healthcare priority.
Children reinfected with Omicron-variant SARS-CoV-2 were twice as likely to develop long COVID and a range of related symptoms as those infected only once, according to a retrospective cohort study of nearly half a million U.S. children.
Relative risk of developing post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was 2.08 (95% CI 1.68-2.59) times greater among those with second COVID-19 infections compared with those with just one infection, said Yong Chen, PhD, of the University of Pennsylvania in Philadelphia, and colleagues.
Long COVID incidence rates among the kids with only one infection were 903.7 per million per 6 months, compared with a rate of 1,883.7 per million among those who had a second infection, they noted in Lancet Infectious Diseases.
That roughly twofold increased relative risk after reinfection held across subgroups, including among children and adolescents who were either vaccinated or unvaccinated.
"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," Chen and colleagues wrote.
The study may offer another message: Long COVID may be a long-term problem among kids.
"The take-home message from this study is clear: Long COVID is here to stay, even in children, and can be exacerbated by reinfections and sustained by high viral circulation," Danilo Buonsenso, MD, PhD, of Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, said in an accompanying editorial. "Governments, healthcare systems, and funding bodies must act now by prioritizing long COVID as a major medical and research focus, enabling access to care, and ensuring children are not left behind."
Reinfection's greater risk also held up in a range of potential long COVID-related conditions and symptoms. Compared with one infection, reinfection was linked to a relative risk of 3.6 (95% CI 1.46-8.86) for myocarditis, 2.83 (95% CI 1.41-5.67) for changes in taste and smell, 2.28 (95% CI 1.71-3.04) for thrombophlebitis and thromboembolism, 1.96 (95% CI 1.69-2.28) for heart disease, and 1.90 (95% CI 1.38-2.61) for acute kidney injury.
Vaccination can cut long COVID risk by preventing infections, Chen and colleagues noted. But pediatric vaccination rates remain low, as does booster uptake in older children. "Strengthening public health messaging and expanding access to vaccination might help to reduce the burden of PASC in children," they said.
Prevention won't be enough to counter long COVID's public health impact, Buonsenso cautioned. "Finding a cure for long COVID needs to become a top research and healthcare priority," he said. "Dedicated pediatric long COVID research centers are urgently needed to facilitate access to future trials and ensure early diagnosis, symptom management, and psychosocial support."
The researchers analyzed electronic health records on 465,717 children and adolescents in the Researching COVID to Enhance Recovery (RECOVER) Initiative, derived from 40 U.S. children's hospitals and health centers for patients younger than 21 years. Eligible participants had a documented COVID-19 infection after Jan. 1, 2022, when SARS-CoV-2 Omicron variants had become dominant. SARS-CoV-2 infections were determined by positive PCR, serology, antigen tests, or COVID-19 diagnoses. The study ran from January 2022 to October 2023.
The primary endpoint was a clinician-documented long COVID diagnosis within 90 to 179 days after infection.
The study's secondary endpoints were 24 conditions and symptoms that may be associated with long COVID in pediatric patients. Other increased relative risks with a second infection were observed for fluid and electrolyte disturbance, arrhythmias, abnormal liver enzymes, fatigue and malaise, headache, postural orthostatic tachycardia syndrome or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory or cardiovascular signs and symptoms, and mental ill health, along with abdominal, general, chest, and musculoskeletal pain.
Patients' mean age was 8.2 years, and 50.2% of patients were male. Among the one-infection group, 42% were white, 15.3% were Black, 24.1% were Hispanic, and 5.4% were Asian American and Pacific Islanders. Among the reinfection group, those percentages were 45.4%, 15.7%, 25.5%, and 3.8%, respectively.
There were 208 long COVID diagnoses among the 407,300 children and adolescents with one infection, and 134 diagnoses among the 58,417 with a second infection.
Second infections were more common among adolescents ages 12 to 20 years, who accounted for 42% of all reinfections. Reinfection patients were also more likely to have obesity or a complex chronic condition.
Study limitations include missing at-home test results not captured in electronic health records, variability in providers' timing of long COVID diagnoses, and the possibility of greater long COVID documentation among reinfection patients, given that they tended to have greater healthcare utilization.
Disclosures
The NIH funded the study.
Chen had no disclosures. Co-authors reported relationships with AstraZeneca, Seqirus, Gilead, Sanofi, the Pediatric Infectious Diseases Society, GSK, UpToDate, NIH, Joan and Sanford I. Weill Medical College of Cornell University, Patient-Centered Outcomes Research Institute, the University of Missouri, and the i2b2 tranSMART Foundation.
Buonsenso disclosed grants from Pfizer and Roche.
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