Most people now view Covid-19 as more of a nuisance than a danger, thanks to vaccines and past exposure to the virus – all of which have built up our immunity – but ongoing research suggests that multiple Covid infections pose a risk for developing long Covid, reports TIME Magazine.
In the largest long Covid study of young people to date, scientists led by a team at the University of Pennsylvania, report that young people who got infected twice were then twice as likely as those who were only infected once to develop long Covid symptoms that affect major organs like the heart, kidney and lungs, as well as taste and smell.
For the ongoing research project, called RECOVER, which is funded by the National Institutes of Health, Yong Chen, Professor of Biostatistics and director of the Centre for Health AI and Synthesis of Evidence (CHASE) at the University of Pennsylvania, and his colleagues focused on people 21 and younger to understand how Covid-19 reinfection affects health.
“People think reinfections don’t matter as much, and don’t take them seriously,” Chen said. “Our primary message is that reinfections still matter, and you should do what you can to avoid this by getting a vaccine or wearing a mask.”
The study, published in The Lancet, involved data collected from more than 460 000 children, adolescents and young adults from 40 paediatric hospitals who were diagnosed with a first Covid-19 infection around January 2022; some went on to develop a second infection after that.
At the end of 2023, the researchers compared the group with only one infection to the group with a second infection, focusing on long Covid-like symptoms such as abdominal pain, respiratory distress, changes in taste and smell, fatigue, chest pain, myocarditis, or irregular heartbeat.
Those who developed a second infection were more than twice as likely as the group with only one infection to get a diagnosis of long Covid, and the reinfected people were nearly three times as likely to report changes in taste and smell as those who’d only had one infection.
This risk remained regardless of whether people were vaccinated or not, or regardless of how severe their infections were.
However, “vaccination status” referred to whether people had been vaccinated before the study period, not how recently they had received the shot. (The study was also initiated before the first updated vaccines, targeting Omicron, were available.)
The authors emphasise that the results do not suggest that vaccines do not help to reduce the risk of long Covid. Rather, the data show that children who were vaccinated were much less likely to get Covid-19 in the first place and were also less likely to get reinfected than unvaccinated children.
Getting vaccinated, Chen said, was an important first step in protecting against possible long Covid.
However, the study shows that even if you’re vaccinated, reinfection poses a significant enough risk to double your chances of developing long Covid compared with just getting it once.
“The message is about how seriously you should treat your potential risk of getting a second infection,” he said.
These results, along with other research, suggest that there might be a cumulative harmful effect of repeat Covid-19 infections on the body, and scientists are trying to better understand those potential long-term effects.
Chen is also continuing the work to study what effect getting vaccinated after a first infection might have on not just the risk of additional infections, but on the development of long Covid as well.
Study details
Long Covid associated with SARS-CoV-2 reinfection among children and adolescents in the Omicron era (RECOVER-EHR): a retrospective cohort study
Bingyu Zhang, Qiong Wu, Ravi Jhaveri et al.
Published in The Lancet on 30 September 2025
Summary
Background
Post-acute sequelae of SARS-CoV-2 infection (PASC) remain a major public health challenge. Although previous studies have focused on characterising PASC in children and adolescents after an initial infection, the risks of PASC after reinfection with the Omicron variant remain unclear. We aimed to assess the risk of PASC diagnosis (U09.9) and symptoms and conditions potentially related to PASC in children and adolescents after a SARS-CoV-2 reinfection during the omicron period.
Methods
This retrospective cohort study used data from 40 children's hospitals and health institutions in the USA participating in the Researching Covid to Enhance Recovery (RECOVER) Initiative. We included patients younger than 21 years at the time of cohort entry; with documented SARS-CoV-2 infection after Jan 1, 2022; and who had at least one health-care visit within 24 months to 7 days before the first infection. The second SARS-CoV-2 infection was confirmed by positive PCR, antigen tests, or a diagnosis of COVID-19 that occurred at least 60 days after the first infection. The primary endpoint was a clinician-documented diagnosis of PASC (U09.9). Secondary endpoints were 24 symptoms and conditions previously identified as being potentially related to PASC. We used the modified Poisson regression model to estimate the relative risk (RR) between the second and first infection episodes, adjusted for demographic, clinical, and health-care utilisation factors using exact and propensity-score matching.
Findings
We identified 407 300 (87·5%) of 465 717 eligible children and adolescents with a first infection episode and 58 417 (12·5%) with a second infection episode from Jan 1, 2022, to Oct 13, 2023, in the RECOVER database. 233 842 (50·2%) patients were male and 231 875 (49·8%) were female. The mean age was 8·17 years (SD 6·58). The incident rate of PASC diagnosis (U09.9) per million people per 6 months was 903·7 (95% CI 780·9–1026·5) in the first infection group and 1883·7 (1565·1–2202·3) in the second infection group. Reinfection was associated with a significantly increased risk of an overall PASC diagnosis (U09.9) (RR 2·08 [1·68–2·59]) and a range of symptoms and conditions potentially related to PASC (RR range 1·15–3·60), including myocarditis, changes in taste and smell, thrombophlebitis and thromboembolism, heart disease, acute kidney injury, fluid and electrolyte disturbance, generalised pain, arrhythmias, abnormal liver enzymes, chest pain, fatigue and malaise, headache, musculoskeletal pain, abdominal pain, mental ill health, POTS or dysautonomia, cognitive impairment, skin conditions, fever and chills, respiratory signs and symptoms, and cardiovascular signs and symptoms.
Interpretation
Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long Covid to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies.
See more from MedicalBrief archives:
US agency launches ‘overdue’ long Covid clinical trials
Ongoing challenge to understand – and treat – long Covid