Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective [...], 2025, Zhang+

SNT Gatchaman

SNT Gatchaman

Senior Member (Voting Rights)
Staff member
Now published, see post #5
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Reinfection with SARS-CoV-2 in the Omicron Era is Associated with Increased Risk of Post-Acute Sequelae of SARS-CoV-2 Infection: A RECOVER-EHR Cohort Study
Bingyu Zhang; Qiong Wu; Ravi Jhaveri; Ting Zhou; Michael J. Becich; Yuriy Bisyuk; Frank Blanceró; Elizabeth A. Chrischilles; Cynthia H. Chuang; Linday G. Cowell; Daniel Fort; Carol R. Horowitz; Susan Kim; Nathalia Ladino; David M. Liebovitz; Mei Liu; Abu S. M. Mosa; Hayden T. Schwenk; Srinivasan Suresh; Bradley W. Taylor; David A. Williams; Jeffrey S. Morris; Christopher B. Forrest; Yong Chen; the RECOVER Consortium

IMPORTANCE
Post-acute sequelae of SARS-CoV-2 infection (PASC) remains a major public health challenge. While previous studies have focused on characterizing PASC and identifying its subphenotypes in children and adolescents following an initial SARS-CoV-2 infection, the risks of PASC with Omicron-variant reinfections remain unclear. Using a real-world data approach, this study investigates the risks of PASC following reinfections during the Omicron phase in the pediatric population.

OBJECTIVE
To investigate the risks of PASC diagnosis and 24 PASC symptoms and conditions after reinfection of SARS-CoV-2 during Omicron period in the pediatric population.

DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data from the RECOVER consortium comprising 40 children9s hospitals and health institutions in U.S. between January 2022 and October 2023.

EXPOSURES
A second SARS-CoV-2 infection, confirmed by a positive polymerase-chain-reaction (PCR) or antigen tests, or a diagnose of COVID-19, occurring at least 60 days after the initial infection, compared to the initial infection.

MAIN OUTCOMES AND MEASURES
PASC was identified using two approaches: (1) the ICD-10-CM diagnosis code U09.9 and (2) a symptom-based definition including 24 physician-identified symptoms and conditions. Absolute risks of incident PASC were reported, and relative risks (RRs) were calculated by comparing the second infection episode with the first infection episode groups using a modified Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through exact matching and propensity scoring matching.

RESULTS
A total of 465,717 individuals under 21 years old (mean [SD] age 8.17 [6.58] years; 52% male) were included. Compared to the first infection, a second infection was associated with significantly increased risk of an overall PASC diagnosis (RR, 2.08; 95% confidence interval [CI], 1.68-2.59), and with many specific conditions including: myocarditis (RR, 3.60; 95% CI, 1.46-8.86); changes in taste and smell (RR, 2.83; 95% CI, 1.41-5.67); thrombophlebitis and thromboembolism (RR, 2.28; 95% CI, 1.71-3.04); heart disease (RR, 1.96; 95% CI, 1.69 to 2.28); acute kidney injury (RR, 1.90; 95% CI, 1.38 to 2.61); fluid and electrolyte (RR, 1.89; 95% CI, 1.62 to 2.20); generalized pain (RR, 1.70; 95% CI, 1.48 to 1.95); arrhythmias (RR, 1.59; 95% CI, 1.45-1.74); abnormal liver enzyme (RR, 1.56; 95% CI, 1.24 to 1.96); fatigue and malaise (RR, 1.50; 95% CI, 1.38 to 1.64); musculoskeletal pain (RR, 1.45; 95% CI, 1.37 to 1.54); abdominal pain (RR, 1.42; 95% CI, 1.34 to 1.50); postural orthostatic tachycardia syndromes (POTS)/dysautonomia (RR, 1.35; 95% CI, 1.20 to 1.51); cognitive functions (RR, 1.32; 95% CI, 1.15 to 1.50); and respiratory signs and symptoms (RR, 1.29; 95% CI, 1.25 to 1.33). The risks were consistent across various organ systems, including cardiovascular, respiratory, gastrointestinal, neurological, and musculoskeletal systems.

CONCLUSIONS AND RELEVANCE
Children and adolescents face significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings suggest a cumulative risk of PASC and highlight the urgent need for targeted prevention strategies to reduce reinfections, which includes an increased emphasis on initial or re-vaccination of children.


Link | PDF (Preprint: MedRxiv) [Open Access]
 
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It seems like symptoms are much more common than a PASC diagnosis.
The data indicate that second infection episode individuals generally have higher incidences. For example, the PASC diagnosis showed 903.7 and 1883.7 incidence rates per million persons per 6 months in the first and second infection groups, respectively. The highest incidence rate observed was respiratory signs and symptoms, with a rate of 61008.2 and 78342.3 in the first and second infection groups per million persons per 6 months.
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Table 2 (low quality):
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Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study

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.

 
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Danilo Buonseno has written a comment about the study for the Lancet

Long COVID is here to stay - even in children

Quote:

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. Governments, health-care systems, and funding bodies must act now by prioritising long COVID as a major medical and research focus, enabling access to care, and ensuring children are not left behind. Without decisive action, the long-term societal cost of long COVID will continue to rise.
 
Without decisive action, the long-term societal cost of long COVID will continue to rise.​

FFS, when are governments and the general community going to accept that improving indoor air quality, and basic masking, are two of the best and most sustainable protections we have against all air-borne infectious diseases, which are one of our greatest ongoing health threats and costs?

But for some perverse reason both have become so toxic that you are barely allowed to even mention them anymore, let alone get a fair hearing.

Few things in my life have disappointed me more than our collective failure to accept and implement these well established protections.

And there is plenty of blame to go around for that, including the health authorities' initial failure to recommend masks during the early stages of Covid.
 
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Sean said:
And there is plenty of blame to go around for that, including the health authorities' initial failure to recommend masks during the early stages of Covid.​
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They don't even recommend masks now. Its worse I think because they now use surgical masks instead of FFP3's for known concerns like TB after the standard was changed in 2020 to conserve the FFP3 masks. Mitigations have gone backwards and once again we find cochrane is a large part responsible for disinformation on masking.
 
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There is a giant gulf of a gap that has appeared on the various studies on prevalence. The research studies show very high prevalences especially this year, the meta studies of those equally show its not an isolated one off but something many studies are finding. Then you have the population studies which show a lot of people think they have Long Covid but most people are unsure, likely due to a lack of public messaging. Then you have the medical studies from hospitals and such which show this tiny number of people and are largely entirely focussed on PASC, the post severe intervention condition.

These studies just show that medicine isn't actually looking very well, its not reporting the symptoms let alone the diagnoses and that directly aligns with what all the patients are saying as well.
 
Kalliope said:
Danilo Buonseno has written a comment about the study for the Lancet

Long COVID is here to stay - even in children

Quote:

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. Governments, health-care systems, and funding bodies must act now by prioritising long COVID as a major medical and research focus, enabling access to care, and ensuring children are not left behind. Without decisive action, the long-term societal cost of long COVID will continue to rise.
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The Lancet publishing this, with zero mention of ME/CFS and the fact that thousands have warned about this, with copious data, to no effect has the same impact on me as people who sell weapons to two sides of a war because it's good for business. And I think the author actually is on the right side of things, possibly wrote it and was asked to remove it, because we know it's been happening systematically.

Except this is all without any actual business. Humans will sell, exploit or doom people for money, this is known. We are easy to corrupt. Recently some rich comedians made controversy for participating in a comedy festival in a rich authoritarian country, excusing it saying "they pay me enough to look the other way". But here it's happening without a single person actually benefiting from it. Everyone employed at this would have plenty of real work to do on other matters. Even the scammers who peddle bullshit pseudoscience are probably losing a lot out of this.

And truly the only lesson learned from the AIDS crisis is that you have to crush a patient movement hard, make them deeply unpopular, target of derision, and nothing else.
 
www.eurekalert.org

The Lancet Infectious Diseases: New study suggests risk of long COVID in children may be twice as high after a second infection

A new study published in The Lancet Infectious Diseases involving over 460,000 children and adolescents across 40 paediatric hospitals in the USA suggests that children who were infected with COVID-19 for the second time during the Omicron wave had more than double the risk of developing long COVID.
www.eurekalert.org

News Release 30-Sep-2025

The Lancet Infectious Diseases: New study suggests risk of long COVID in children may be twice as high after a second infection​

Peer-Reviewed Publication
The Lancet


A new study published in The Lancet Infectious Diseases involving over 460,000 children and adolescents across 40 paediatric hospitals in the USA suggests that children who were infected with COVID-19 for the second time during the Omicron wave had more than double the risk of developing long COVID.

Conducted by researchers under the US National Institutes of Health (NIH)-funded RECOVER Initiative*, this is the largest study to date examining the long-term effects of COVID-19 reinfection in young people. The study analysed electronic health records from January 2022 through October 2023, a period dominated by the highly transmissible Omicron variant. Researchers compared health outcomes following children’s first and second documented COVID-19 infections to isolate the risks associated with reinfection.

They found that after a first COVID-19 infection, about 904 children per million developed long COVID within six months. Following a second infection (reinfection), this number more than doubled to approximately 1,884 children per million. The higher risk was observed across many different groups in the study, regardless of whether they were vaccinated, how serious their first illness was, their age, gender, race or ethnicity, or if they were living with overweight or obesity. The authors say this increased risk of long COVID following reinfections highlights the continued importance of preventing COVID-19 infections through vaccination and other protective measures such as masking and social distancing.

Reinfection was linked to a wide range of rare but persistent and sometimes serious conditions potentially associated with long COVID in children, including heart inflammation (myocarditis), blood clots, kidney injury, cognitive difficulties, fatigue, and respiratory problems.

The authors emphasise that while vaccines and other prevention measures may not completely eliminate the risk of contracting COVID-19, they remain the most effective way to prevent both initial infections and reinfections, thereby reducing the risk of long-lasting symptoms in children. They say the study’s findings reinforce the need to strengthen public health efforts to increase COVID-19 vaccination coverage among children and adolescents.

*The NIH’s RECOVER (Researching COVID to Enhance Recovery) Initiative is dedicated to understanding long COVID, developing better treatments, and guiding strategies to protect people of all ages from the prolonged effects of COVID-19.

Journal​

The Lancet Infectious Diseases

DOI​

10.1016/S1473-3099(25)00476-1

Method of Research​

Observational study

Subject of Research​

People

Article Title​

Long COVID associated with SARS-CoV-2 reinfection among children and adolescents in the omicron era (RECOVER-EHR): a retrospective cohort study

Article Publication Date​

30-Sep-2025

COI Statement​

RJ is a consultant for AstraZeneca, Seqirus, Gilead, and Sanofi; receives an editorial stipend from the Pediatric Infectious Diseases Society; research support from GSK; and royalties from Up To Date (Wolters Kluwer). DML received institutional funding from the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Initiative via a subcontract from Joan and Sanford I Weill Medical College of Cornell University (grants office ID SP0072825). ASMM received institutional funding from Patient-Centered Outcomes Research Institute (PCORI) for PCORnet Common Data Model creation, and from the NIH RECOVER Initiative through the University of Missouri as site principal investigator and serves as a board member of the i2b2 tranSMART Foundation, a nonprofit organisation supporting the development of the i2b2 informatics platform. All other authors declare no competing interests.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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www.eurekalert.org

Risk of long COVID in kids doubles after second infection

Children and adolescents were twice as likely to experience long COVID after catching COVID for the second time, compared to their peers with a single previous infection, according to a large study funded by the National Institutes of Health (NIH) and published in Lancet Infectious Diseases...
www.eurekalert.org

News Release 30-Sep-2025

Risk of long COVID in kids doubles after second infection​

Study findings reinforce the importance of COVID vaccination in children

Peer-Reviewed Publication
Ann & Robert H. Lurie Children's Hospital of Chicago


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Children and adolescents were twice as likely to experience long COVID after catching COVID for the second time, compared to their peers with a single previous infection, according to a large study funded by the National Institutes of Health (NIH) and published in Lancet Infectious Diseases. These results run counter to the popular perceptions that COVID in children is "mild" and that reinfections with COVID do not carry the same risk of long COVID that initial infections do.

Among the conditions associated with long COVID in youth, myocarditis (swelling of the heart muscle that can weaken the heart and even prove fatal) was most common with the risk tripling after a second COVID infection compared to the initial infection. Blood clots in children were more than twice as likely after a second COVID infection. Kids were also at increased risk for many other conditions after getting COVID twice, including damaged kidneys, abnormal heartbeats, headache, abdominal pain and severe fatigue.

“The results of this study further support one of the strongest reasons I give patients, families and physicians about getting vaccinated: More vaccines should lead to fewer infections, which should lead to less long COVID,” said co-author Ravi Jhaveri, MD, Head of Pediatric Infectious Diseases at Ann & Robert H. Lurie Children's Hospital of Chicago and Professor of Pediatrics at Northwestern University Feinberg School of Medicine.

Researchers analyzed data from electronic health records (EHR) of more than 465,000 children and adolescents from January 1, 2022, to October 13, 2023, when Omicron was the dominant variant. This study is part of the NIH-funded RECOVER Initiative, which includes 40 U.S. children’s hospitals and health institutions and aims to learn about the long-term effects of COVID. The current study is the first and largest longitudinal EHR-based investigation of long COVID following reinfection in children and adolescents.

“The level of coordination, data sharing, and analysis requires massive infrastructure and sustained support,” said senior author Yong Chen, PhD, a Professor of Biostatistics and the Director of PennCIL at the Perelman School of Medicine at the University of Pennsylvania. “Without this investment, we wouldn’t have had access to such a large and diverse pediatric population, nor the capacity to rigorously evaluate long COVID in a way that is applicable across many different levels of care.”

Moving forward, researchers plan to track data on pediatric patients that span longer periods of time, examine whether newer COVID variants change the risk pattern, and explore specific strategies that might help prevent severe long-term effects.

Dr. Jhaveri holds the Virginia H. Rogers Professorship in Infectious Disease at Lurie Children’s.

Ann & Robert H. Lurie Children’s Hospital of Chicago is a nonprofit organization committed to providing access to exceptional care for every child. It is the only independent, research-driven children’s hospital in Illinois and one of less than 35 nationally. This is where the top doctors go to train, practice pediatric medicine, teach, advocate, research and stay up to date on the latest treatments. Exclusively focused on children, all Lurie Children’s resources are devoted to serving their needs. Research at Lurie Children’s is conducted through Stanley Manne Children’s Research Institute, which is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is the pediatric training ground for Northwestern University Feinberg School of Medicine. It is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report.

Journal​

The Lancet Infectious Diseases
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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