Repeat infections in children and adolescents are linked to a rise in long-term complications, including heart and respiratory problems.
Children who have a second covid infection face more than twice the risk of developing long covid than the risk they face following their first infection, according to the largest study to date on reinfection in young people.
The multicentre retrospective cohort study, conducted within the NIH-funded Researching Covid to Enhance Recovery (RECOVER) Initiative.
The researchers analysed de-identified electronic health record data from more than 460,000 patients younger than 21 years at the time of entry, across 40 US children’s hospitals.
The study period spanned January 2022 through October 2023, when the Omicron variant and its sublineages predominated. The findings were published in The Lancet Infectious Diseases.
The second covid infection was confirmed by positive PCR, antigen tests or a diagnosis of covid that occurred at least 60 days after the first infection.
Researchers compared incident rates of long covid diagnoses and associated clinical sequelae following children’s first versus second documented covid infections. Long covid was defined using established diagnostic coding combined with clinical features consistent with the RECOVER consortium’s framework for paediatric long covid (also known as post-acute sequelae of SARS-CoV-2 infection, or PASC).
Within six months of a primary infection, the incidence rate of long covid was estimated at 904 per million children.
After a second infection, this risk more than doubled to 1884 per million. Reinfection was associated with an adjusted hazard ratio (aHR) greater than 2.0 for long covid relative to primary infection, and this association persisted after controlling for covariates including age, sex, race/ethnicity, vaccination status, baseline comorbidities (e.g., overweight/obesity) and initial illness severity.
Notably, the increased risk was consistent across all demographic and clinical subgroups examined.
Reinfection was linked to a heterogeneous range of sequelae, including myocarditis, thromboembolic events, acute kidney injury, neurocognitive difficulties, persistent fatigue and respiratory impairment. While the absolute risk remains low, the potential severity of these outcomes raised concern, the authors wrote.
“These findings emphasise the ongoing risk of PASC with reinfection, regardless of severity, and suggest that the risk of PASC might be cumulative with each successive infection,” they wrote.
“Our findings align with emerging evidence on immune waning post-infection. Although T-cell responses remain stable, neutralising antibody concentrations decline over time, possibly compromising immunity upon reinfection.
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“During the Omicron era, protection from natural infection diminished more rapidly, with reinfections becoming more common, especially among younger adults aged 18–49 years.
“These dynamics elevate the need to understand reinfection risks in children, a group increasingly affected yet understudied in this context.
“Previous paediatric studies further support the clinical relevance of our findings. Long covid in paediatric populations has been associated with proteomic biosignatures, POTS, exercise intolerance, vascular problems and CNS issues.
“Our real-world data add to this literature by showing that post-acute sequelae persist across reinfections and continue to impose a measurable clinical burden.”
They noted that although covid vaccines did not guarantee absolute immunity from infection, they remained the most effective strategy for reducing both primary and repeat infections and, consequently, the risk of long covid in paediatric populations.
They concluded that these findings support intensifying vaccination efforts and maintaining layered public health measures, particularly in settings where transmission remains high.
The RECOVER Initiative continues to investigate the natural history, risk factors and pathophysiology of long covid, with the aim of informing preventive strategies and developing evidence-based therapies for affected children and adults.
There have been 163,261 confirmed covid cases reported to the National Notifiable Disease Surveillance System so far this year (as of 8 October 2025). Of these 30,926 have been people aged 19 years and younger. The 0-4 years age bracket has had the bulk of these cases (15,821).
In 2024 there were a total of 341,840 reported covid cases, including 52,588 people aged 19 years and younger. Following this year’s trend, just under half of these (25,357) were cases in the 0-4 years age bracket.
