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Early identification of patients at risk for severe disease, including myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS), is crucial for timely and adequate care. This monocentric, observational registry study, performed at a tertiary pediatric hospital in Germany, included CYP aged 7\u201325\u00a0years with PCCcyp at diagnosis. Standardized clinical assessment tools and patient-reported outcome measures were applied, including the novel Munich Long COVID Symptom Questionnaire (MLCSQ). Severe PCC was defined by chronic symptom clusters, Fatigue Severity Scale (FSS), Total Composite Autonomic Symptom Score-31 (COMPASS-31), SF-36 composite scores, Bell Score, and confirmed ME\/CFS diagnosis. Among 120 participants, severe PCCcyp was associated with a higher number of acute symptoms (OR\n                    <jats:sub>adj<\/jats:sub>\n                    1.22,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001), acute orthostatic intolerance (OR\n                    <jats:sub>adj<\/jats:sub>\n                    9.87,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.002), acute trouble concentrating (OR\n                    <jats:sub>adj<\/jats:sub>\n                    11.8,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.005), and female sex (OR 3.31,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.031). Categorizing acute symptoms at a threshold of\u2009\u2265\u200912 yielded optimal model performance (AUC 0.857; sensitivity 65.6%; specificity 90.2%). ME\/CFS was diagnosed in 24% of participants, all within the severe PCCcyp cluster, and was characterized by greater acute symptom complexity, more fatigue, more autonomic symptoms, and poorer function.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    : The number and pattern of acute symptoms during SARS-CoV-2 infection may serve as early, specific predictors of severe PCCcyp. Patients with\u2009\u2265\u200912 acute symptoms should be closely monitored to enable early diagnosis of severe PCCcyp and ME\/CFS. A distinct cluster of severely affected patients, frequently with ME\/CFS, was identified.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Trial registration<\/jats:italic>\n                    : ClinicalTrials.gov: NCT05638724; Ethics approval (511\/21, 2025\u2013465-S-SB).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td colspan=\"3\">\n                              <jats:bold>What is Known:<\/jats:bold>\n                              \u2022\n                              <jats:italic>Post-COVID condition in children and young people (PCCcyp) is increasingly reported, yet clinicians lack reliable markers to identify patients at risk of severe disease early on<\/jats:italic>\n                              .\n                            <\/jats:td>\n                          <\/jats:tr>\n                          <jats:tr>\n                            <jats:td colspan=\"3\">\n                              <jats:bold>What is New:<\/jats:bold>\n                              \u2022\n                              <jats:italic>Severe PCCcyp in pediatric patients can be predicted during the acute phase of the SARS-CoV-2 infection<\/jats:italic>\n                              .\u2022\n                              <jats:italic>A high acute symptom load (\u2265\u200912 symptoms), female sex, acute orthostatic intolerance, and acute trouble concentrating predict severe PCCcyp<\/jats:italic>\n                              .\u2022\n                              <jats:italic>24% of patients fulfilled ME\/CFS criteria\u2014all within the severe cluster\u2014highlighting a distinct high-risk subgroup that necessitates early stratification and care<\/jats:italic>\n                              .\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s00431-026-06995-3","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:14:47Z","timestamp":1777932887000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Risk factors for severe post-COVID condition in children, adolescents, and young 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Ethical approval for the MLC-R registry study was granted on 23 August 2021 by the Ethics Committee of the Technical University of Munich (TUM) (511\/21). The data analysis received separate ethical approval from the Ethics Committee of the TUM on 5 September 2025 (2025\u2013465-S-SB).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all subjects (or their legal guardian) involved in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Written informed consent was obtained from all subjects (or their legal guardians) involved in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors have completed the ICMJE uniform disclosure form. U.B. reports research funding from the Bavarian State Ministry of Health and Care, the Bavarian State Ministry of Science and Art, the German Center for Infection Research (DZIF), the Federal Ministry of Research, Technology and Space, the Federal Ministry of Health, and the Federal Joint Committee. CS received grants from the Federal Ministry of Health, consulting fees from Celltrend, and payment or honoraria from Bayer, Fresenius, Roche, Celltrend, Haus\u00e4rzteverband Berlin, AGBAN AKADEMIE, and Berufsverband Dt. Internisten. Further, CS is a participant in advisory boards at Berlin cures and the Federal Institute for Drugs and Medical Devices (BfArM). M.A. received financial compensation from BioNTech and Pfizer for participating in advisory board meetings on Long COVID. C.C. received personal payment from the Austrian Chamber of Pharmacists for delivering vaccination training lectures. Q.D. and LC.P. report an MD scholarship from the German Center for Infection Research. LC.P. received a travel scholarship from the Lost Voices Foundation to attend the 2023 IACFS\/ME Research and Clinical Conference. N.T. serves as Vice President of the German Society of Pediatric Infectious Diseases (DGPI). U.B. and C.S. are members of the medical advisory board of the German association for ME\/CFS. All other authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"344"}}