{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:03:53Z","timestamp":1776420233528,"version":"3.51.2"},"posted":{"date-parts":[[2025,3,30]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DESIGN, SETTING, AND PARTICIPANTS<\/jats:title>\n                  <jats:p>This retrospective cohort study used data from the RECOVER consortium comprising 40 children\u2019s hospitals and health institutions in U.S. between January 2022 and October 2023.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>EXPOSURES<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>MAIN OUTCOMES AND MEASURES<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS AND RELEVANCE<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Question<\/jats:title>\n                    <jats:p>Do children and adolescents face an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) following reinfection during the Omicron era?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>During the post-acute phase, children and adolescents with reinfection are at statistically significant increased risk of incident PASC outcomes, including an overall PASC diagnosis and 24 most commonly complaints\/symptoms\/diagnoses associated with PASC. The risks remained consistent across different demographic and clinical subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Meaning<\/jats:title>\n                    <jats:p>These findings underscore the significant long-term health risks associated with SARS-CoV-2 reinfection in children and adolescents. Public health strategies should prioritize reinfection prevention, including enhanced vaccination efforts, to mitigate the burden of PASC in the pediatric population.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.28.25324858","type":"posted-content","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T15:30:11Z","timestamp":1743348611000},"source":"Crossref","is-referenced-by-count":7,"title":["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"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7176-249X","authenticated-orcid":false,"given":"Bingyu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Jhaveri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Becich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuriy","family":"Bisyuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Blancer\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Chrischilles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia H.","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linday G.","family":"Cowell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Fort","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol R.","family":"Horowitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalia","family":"Ladino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Liebovitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abu S. 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