{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:07:18Z","timestamp":1783969638406,"version":"3.55.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medizinische Hochschule Hannover (MHH)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Identifying symptom clusters in post-COVID-19 condition (PCC) is a necessary step toward for developing more targeted therapeutic interventions for this heterogeneous condition. Therefore, the aim of this study was to identify symptom clusters based on 14 specific PCC symptoms, accounting for both symptom presence and impairment. The identified clusters were then compared with respect to sociodemographic, clinical, and psychological factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A clinical sample of individuals with a PCC diagnosis lasting at least one year was included (final\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091673). A two-step cluster analysis was performed to identify symptom clusters. Subsequent comparisons between clusters were performed using Mann-Whitney U tests for continuous variables and chi-square tests for categorical variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of four clusters were identified: two symptom burden clusters (\n                      <jats:italic>Systemic<\/jats:italic>\n                      (high burden) and\n                      <jats:italic>Few Symptoms<\/jats:italic>\n                      (low burden)) and two symptom-specific clusters (\n                      <jats:italic>Neurocognitive<\/jats:italic>\n                      and\n                      <jats:italic>Pain<\/jats:italic>\n                      ). Participants in the\n                      <jats:italic>Systemic<\/jats:italic>\n                      (high burden) cluster exhibited the highest levels of psychological distress, reported the most severe fatigue, and were most frequently unemployed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In PCC, different symptom clusters can be identified that differ in terms of sociodemographic, clinical, and psychological factors. Future research using biomarker, imaging, and longitudinal designs is needed to determine whether these symptom-based clusters correspond to distinct biological subgroups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08582-4","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T02:34:46Z","timestamp":1783737286000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Symptom-based clusters in people with post-COVID-19 condition (PCC)"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5978-1029","authenticated-orcid":false,"given":"Charlotte","family":"Kuczyk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Herrmann-Lingen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Stolz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Krauth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Burger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jona Theodor","family":"Stahmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariel","family":"N\u00f6hre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Debener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"K\u00e4ufer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Richter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Derad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hellmich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"de Zwaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"issue":"7","key":"8582_CR1","doi-asserted-by":"publisher","first-page":"e231933","DOI":"10.1001\/jamahealthforum.2023.1933","volume":"4","author":"GM Katz","year":"2023","unstructured":"Katz GM, Bach K, Bobos P, Cheung A, D\u00e9cary S, Goulding S, Herridge MS, McNaughton CD, Palmer KS, Razak FA, Zhang B, Quinn KL. Understanding How Post-COVID-19 Condition Affects Adults and Health Care Systems. JAMA Health Forum. 2023;4(7):e231933. https:\/\/doi.org\/10.1001\/jamahealthforum.2023.1933.","journal-title":"JAMA Health Forum"},{"key":"8582_CR2","doi-asserted-by":"publisher","unstructured":"Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133-146. https:\/\/doi.org\/10.1038\/s41579-022-00846-2. Erratum in: Nat Rev Microbiol. 2023;21(6):408. https:\/\/doi.org\/10.1038\/s41579-023-00896-0.","DOI":"10.1038\/s41579-022-00846-2"},{"key":"8582_CR3","doi-asserted-by":"publisher","unstructured":"Boaventura P, Macedo S, Ribeiro F, Jaconiano S, Soares P. Post-COVID-19 condition: where are we now? Life (Basel). 2022;12(4):517. https:\/\/doi.org\/10.3390\/life12040517.","DOI":"10.3390\/life12040517"},{"issue":"11","key":"8582_CR4","doi-asserted-by":"publisher","first-page":"e32058","DOI":"10.7759\/cureus.32058","volume":"14","author":"SA Alghamdi","year":"2022","unstructured":"Alghamdi SA, Alfares MA, Alsulami RA, Alghamdi AF, Almalawi AM, Alghamdi MS, Hazazi HA. Post-COVID-19 Syndrome: Incidence, Risk Factor, and the Most Common Persisting Symptoms. Cureus. 2022;14(11):e32058. https:\/\/doi.org\/10.7759\/cureus.32058.","journal-title":"Cureus"},{"key":"8582_CR5","doi-asserted-by":"publisher","unstructured":"Domingo FR, Waddell LA, Cheung AM, Cooper CL, Belcourt VJ, Zuckermann AM, Corrin T, Ahman R, Boland L, Laprise C, Idzerda L, Khan A, Morissette K, Garcia AJ. Prevalence of long-term effects in individuals diagnosed with COVID-19: an updated living systematic review. medRxiv. 2021 Jun. https:\/\/doi.org\/10.1101\/2021.06.03.21258317.","DOI":"10.1101\/2021.06.03.21258317"},{"issue":"1","key":"8582_CR6","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1080\/07853890.2022.2076901","volume":"54","author":"D Castanares-Zapatero","year":"2022","unstructured":"Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, Primus-de Jong C, Cleemput I, Van den Heede K. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022;54(1):1473\u201387. https:\/\/doi.org\/10.1080\/07853890.2022.2076901.","journal-title":"Ann Med"},{"issue":"1","key":"8582_CR7","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s12985-022-01891-2","volume":"19","author":"GE Batiha","year":"2022","unstructured":"Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Welson NN. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J. 2022;19(1):158. https:\/\/doi.org\/10.1186\/s12985-022-01891-2.","journal-title":"Virol J"},{"key":"8582_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijid.2023.05.003","volume":"134","author":"P Kuodi","year":"2023","unstructured":"Kuodi P, Gorelik Y, Gausi B, Bernstine T, Edelstein M. Characterization of post-COVID syndromes by symptom cluster and time period up to 12 months post-infection: A systematic review and meta-analysis. Int J Infect Dis. 2023;134:1\u20137. https:\/\/doi.org\/10.1016\/j.ijid.2023.05.003.","journal-title":"Int J Infect Dis"},{"issue":"12","key":"8582_CR9","doi-asserted-by":"publisher","first-page":"102994","DOI":"10.1016\/j.jiph.2025.102994","volume":"18","author":"T Grafstr\u00f6m","year":"2025","unstructured":"Grafstr\u00f6m T, Barros GWF, Persson IL, Sundh J, Forsell MNE, Ahlm C, M\u00e5nsson E, Tevell S, Lind A, Normark J, Cajander S. Post COVID-19 condition phenotypes: A prospective cohort study identifying four symptom clusters and their impact on long-term outcomes. J Infect Public Health. 2025;18(12):102994. https:\/\/doi.org\/10.1016\/j.jiph.2025.102994.","journal-title":"J Infect Public Health"},{"key":"8582_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02353-x","author":"M Aid","year":"2026","unstructured":"Aid M, et al. Long COVID involves activation of proinflammatory and immune exhaustion pathways. Nat Immunol. 2026. https:\/\/doi.org\/10.1038\/s41590-025-02353-x.","journal-title":"Nat Immunol"},{"key":"8582_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2024.108507","author":"EC Rusu","year":"2024","unstructured":"Rusu EC, et al. Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights. Comput Biol Med. 2024. https:\/\/doi.org\/10.1016\/j.compbiomed.2024.108507. | PMID: 38657468.","journal-title":"Comput Biol Med"},{"key":"8582_CR12","doi-asserted-by":"publisher","unstructured":"Mohammed Y, et al. Proteomic evolution from acute to post-COVID-19 conditions. J Proteome Res. 2024. https:\/\/doi.org\/10.1021\/acs.jproteome.3c00324 | PMID: 38048423.","DOI":"10.1021\/acs.jproteome.3c00324"},{"key":"8582_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2024.102571","author":"A Seco-Gonz\u00e1lez","year":"2024","unstructured":"Seco-Gonz\u00e1lez A, et al. Proteomic analysis of post-COVID condition: Insights from plasma and pellet blood fractions. J Infect Public Health doi. 2024. https:\/\/doi.org\/10.1016\/j.jiph.2024.102571. | PMID: 39486386.","journal-title":"J Infect Public Health doi"},{"key":"8582_CR14","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae318","author":"NJ Epsi","year":"2025","unstructured":"Epsi NJ, et al. Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae. J Infect Dis. 2025. https:\/\/doi.org\/10.1093\/infdis\/jiae318.","journal-title":"J Infect Dis"},{"key":"8582_CR15","doi-asserted-by":"publisher","DOI":"10.1111\/all.16526","author":"N Baalbaki","year":"2025","unstructured":"Baalbaki N, et al. The Omics Landscape of Long COVID\u2014A. Compr Syst Rev Allergy. 2025. https:\/\/doi.org\/10.1111\/all.16526.","journal-title":"Compr Syst Rev Allergy"},{"issue":"12","key":"8582_CR16","doi-asserted-by":"publisher","first-page":"e0316335","DOI":"10.1371\/journal.pone.0316335","volume":"19","author":"M Brinkmann","year":"2024","unstructured":"Brinkmann M, Stolz M, Herr A, Herrmann-Lingen C, Koch I, M\u00fcller C, M\u00fcller F, Sekanina U, Stahmeyer JT, de Zwaan M, Krauth C, Schneider N. Care for post-COVID-19 condition in Germany from the perspectives of patients, informal caregivers and general practitioners: Study protocol for a mixed methods study. PLoS ONE. 2024;19(12):e0316335. https:\/\/doi.org\/10.1371\/journal.pone.0316335.","journal-title":"PLoS ONE"},{"issue":"4","key":"8582_CR17","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1016\/S1473-3099(21)00703-9","volume":"22","author":"JB Soriano","year":"2022","unstructured":"Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22(4):e102\u20137. https:\/\/doi.org\/10.1016\/S1473-3099(21)00703-9.","journal-title":"Lancet Infect Dis"},{"key":"8582_CR18","unstructured":"World Health Organization (WHO) clinical case definition working group on post COVID-19 condition. A clinical case definition of post COVID-19 condition by a Delphi consensus. Geneva: World Health Organization; 2021. https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1"},{"issue":"1\u20132","key":"8582_CR19","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jad.2009.06.019","volume":"122","author":"B L\u00f6we","year":"2010","unstructured":"L\u00f6we B, Wahl I, Rose M, Spitzer C, Glaesmer H, Wingenfeld K, Schneider A, Br\u00e4hler E. A 4-item measure of depression and anxiety: validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J Affect Disord. 2010;122(1\u20132):86\u201395. https:\/\/doi.org\/10.1016\/j.jad.2009.06.019.","journal-title":"J Affect Disord"},{"issue":"9\u201310","key":"8582_CR20","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1055\/a-1088-1354","volume":"70","author":"U Berger","year":"2020","unstructured":"Berger U, Kirschner H, Muehleck J, Gl\u00e4ser A, Werner B, Kurz M, Schwager S, Wick K, Strau\u00df B. Kurz-Skala zur Erfassung wahrgenommener sozialer Teilhabe (KsT-5): faktorielle Struktur, interne Konsistenz, inhaltliche und konvergente Validit\u00e4t sowie Normwerte in einer repr\u00e4sentativen Stichprobe [Short Scale Measuring Perceived Social Participation: Factorial Structure, Internal Consistency, Content Validity, Convergent Validity and Standard Values in a Representative German Sample]. Psychother Psychosom Med Psychol. 2020;70(9\u201310):396\u2013404. https:\/\/doi.org\/10.1055\/a-1088-1354. German.","journal-title":"Psychother Psychosom Med Psychol"},{"issue":"10","key":"8582_CR21","doi-asserted-by":"publisher","first-page":"e0186516","DOI":"10.1371\/journal.pone.0186516","volume":"12","author":"ME Beutel","year":"2017","unstructured":"Beutel ME, Br\u00e4hler E, Wiltink J, Michal M, Klein EM, J\u00fcnger C, Wild PS, M\u00fcnzel T, Blettner M, Lackner K, Nickels S, Tibubos AN. Emotional and tangible social support in a German population-based sample: Development and validation of the Brief Social Support Scale (BS6). PLoS ONE. 2017;12(10):e0186516. https:\/\/doi.org\/10.1371\/journal.pone.0186516.","journal-title":"PLoS ONE"},{"issue":"2","key":"8582_CR22","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0022-3999(93)90081-p","volume":"37","author":"T Chalder","year":"1993","unstructured":"Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147\u201353. https:\/\/doi.org\/10.1016\/0022-3999(93)90081-p.","journal-title":"J Psychosom Res"},{"issue":"1","key":"8582_CR23","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1026\/1616-3443\/a000010","volume":"9","author":"A Martin","year":"2010","unstructured":"Martin A, Staufenbiel T, Gaab J, Rief W, Br\u00e4hler E. Messung chronischer Ersch\u00f6pfung\u2013Teststatistische Pr\u00fcfung der Fatigue Skala (FS). Z f\u00fcr klinische Psychologie und Psychother. 2010;9(1):33\u201344. https:\/\/doi.org\/10.1026\/1616-3443\/a000010.","journal-title":"Z f\u00fcr klinische Psychologie und Psychother"},{"issue":"1","key":"8582_CR24","doi-asserted-by":"publisher","first-page":"2524087","DOI":"10.1080\/07853890.2025.2524087","volume":"57","author":"L Krakau","year":"2025","unstructured":"Krakau L, Wicke F, H\u00e4user W, Beutel ME, Br\u00e4hler E, Hettich-Damm N. Chronic fatigue: psychometric properties and updated norm values of the Chalder fatigue scale in a cross-sectional sample representative of the German population. Ann Med. 2025;57(1):2524087. https:\/\/doi.org\/10.1080\/07853890.2025.2524087.","journal-title":"Ann Med"},{"issue":"3","key":"8582_CR25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3390\/diagnostics8030066","volume":"8","author":"J Cotler","year":"2018","unstructured":"Cotler J, Holtzman C, Dudun C, Jason LA. A Brief Questionnaire to Assess Post-Exertional Malaise. Diagnostics (Basel). 2018;8(3):66. https:\/\/doi.org\/10.3390\/diagnostics8030066.","journal-title":"Diagnostics (Basel)"},{"key":"8582_CR26","doi-asserted-by":"publisher","first-page":"1647040","DOI":"10.3389\/fpsyt.2025.1647040","volume":"16","author":"C Kuczyk","year":"2025","unstructured":"Kuczyk C, N\u00f6hre M, Herrmann-Lingen C, Stolz M, Krauth C, Br\u00e4hler E, Jason LA, de Zwaan M. Reliability and validity of the German version of the DePaul Symptom Questionnaire Post-Exertional Malaise (DSQ-PEM). Front Psychiatry. 2025;16:1647040. https:\/\/doi.org\/10.3389\/fpsyt.2025.1647040.","journal-title":"Front Psychiatry"},{"issue":"1","key":"8582_CR27","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.datak.2007.01.002","volume":"63","author":"R Gelbard","year":"2007","unstructured":"Gelbard R, Goldman O, Spiegler I. Investigating diversity of clustering methods: an empirical comparison. Data Knowl Eng. 2007;63(1):155\u201366. doi: 10 1016\/j.datak 2007 01 002.","journal-title":"Data Knowl Eng"},{"key":"8582_CR28","doi-asserted-by":"crossref","unstructured":"Kent P, Jensen RK, Kongsted A. A comparison of three clustering methods for finding subgroups in MRI, SMS or clinical data: SPSS TwoStep cluster analysis, Latent Gold, and SNOB. BMC Med Res Methodol. 2014;14(1):113.","DOI":"10.1186\/1471-2288-14-113"},{"key":"8582_CR29","unstructured":"Bacher J, Wenzig K, Vogler M. SPSS TwoStep Cluster - a first evaluation. 2nd corr. ed. N\u00fcrnberg: Universit\u00e4t Erlangen-N\u00fcrnberg, Wirtschafts- und Sozialwissenschaftliche Fakult\u00e4t, Sozialwissenschaftliches Institut, Lehrstuhl f\u00fcr Soziologie; 2004. (Arbeits- und Diskussionspapiere \/ Universit\u00e4t Erlangen-N\u00fcrnberg, Sozialwissenschaftliches Institut, Lehrstuhl f\u00fcr Soziologie; 2004-2). https:\/\/nbn-resolving.org\/urn:nbn:de:0168-ssoar-327153"},{"issue":"5","key":"8582_CR30","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373\u201383. https:\/\/doi.org\/10.1016\/0021-9681(87)90171-8.","journal-title":"J Chronic Dis"},{"issue":"5","key":"8582_CR31","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1017\/s0033291700037417","volume":"25","author":"I Hickie","year":"1995","unstructured":"Hickie I, Lloyd A, Hadzi-Pavlovic D, Parker G, Bird K, Wakefield D. Can the chronic fatigue syndrome be defined by distinct clinical features? Psychol Med. 1995;25(5):925\u201335. https:\/\/doi.org\/10.1017\/s0033291700037417.","journal-title":"Psychol Med"},{"key":"8582_CR32","doi-asserted-by":"publisher","unstructured":"Collin SM, Nikolaus S, Heron J, Knoop H, White PD, Crawley E. Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and the Netherlands. J Psychosom Res. 2016;81:14-23. https:\/\/doi.org\/10.1016\/j.jpsychores.2015.12.006. Erratum in: J Psychosom Res. 2023;168:111324. doi: https:\/\/doi.org\/10.1016\/j.jpsychores.2023.111324.","DOI":"10.1016\/j.jpsychores.2015.12.006"},{"key":"8582_CR33","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jpsychores.2017.11.007","volume":"104","author":"SM Collin","year":"2018","unstructured":"Collin SM, Heron J, Nikolaus S, Knoop H, Crawley E. Chronic fatigue syndrome (CFS\/ME) symptom-based phenotypes and 1-year treatment outcomes in two clinical cohorts of adult patients in the UK and the Netherlands. J Psychosom Res. 2018;104:29\u201334. https:\/\/doi.org\/10.1016\/j.jpsychores.2017.11.007.","journal-title":"J Psychosom Res"},{"issue":"1","key":"8582_CR34","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12967-023-03946-6","volume":"21","author":"AW Vaes","year":"2023","unstructured":"Vaes AW, Van Herck M, Deng Q, Delbressine JM, Jason LA, Spruit MA. Symptom-based clusters in people with ME\/CFS: an illustration of clinical variety in a cross-sectional cohort. J Transl Med. 2023;21(1):112. https:\/\/doi.org\/10.1186\/s12967-023-03946-6.","journal-title":"J Transl Med"},{"key":"8582_CR35","doi-asserted-by":"publisher","unstructured":"Moniz M, Ruivinho C, Goes AR, Soares P, Leite A. Long COVID is not the same for everyone: a hierarchical cluster analysis of Long COVID symptoms 9 and 12 months after SARS-CoV-2 test. BMC Infect Dis. 2024;24(1):1001. https:\/\/doi.org\/10.1186\/s12879-024-09896-8. Erratum in: BMC Infect Dis. 2024;24(1):1178. https:\/\/doi.org\/10.1186\/s12879-024-10086-9.","DOI":"10.1186\/s12879-024-09896-8"},{"issue":"1","key":"8582_CR36","doi-asserted-by":"publisher","first-page":"bpae076","DOI":"10.1093\/biomethods\/bpae076","volume":"9","author":"P Mfouth Kemajou","year":"2024","unstructured":"Mfouth Kemajou P, Besse-Hammer T, Lebouc C, Coppieters Y. Cluster analysis identifies long COVID subtypes in Belgian patients. Biol Methods Protoc. 2024;9(1):bpae076. https:\/\/doi.org\/10.1093\/biomethods\/bpae076.","journal-title":"Biol Methods Protoc"},{"key":"8582_CR37","doi-asserted-by":"publisher","DOI":"10.2900\/5489226","volume-title":"Does COVID-19 vaccination reduce the risk and duration of post-COVID-19 condition? Rapid systematic literature review","author":"European Centre for Disease Prevention and Control","year":"2025","unstructured":"European Centre for Disease Prevention and Control. Does COVID-19 vaccination reduce the risk and duration of post-COVID-19 condition? Rapid systematic literature review. Stockholm: ECDC; 2025. https:\/\/doi.org\/10.2900\/5489226."},{"key":"8582_CR38","doi-asserted-by":"publisher","first-page":"1686572","DOI":"10.3389\/fimmu.2025.1686572","volume":"16","author":"GN Guimar\u00e3es","year":"2025","unstructured":"Guimar\u00e3es GN, Brunetti NS, De Lima DG, Proenca-Modena JL, Farias AS. Vaccination and COVID-19: impact on long-COVID. Front Immunol. 2025;16:1686572. https:\/\/doi.org\/10.3389\/fimmu.2025.1686572.","journal-title":"Front Immunol"},{"issue":"1","key":"8582_CR39","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12967-021-02713-9","volume":"19","author":"TT Asprusten","year":"2021","unstructured":"Asprusten TT, Sletner L, Wyller VBB. Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers. J Transl Med. 2021;19(1):48. https:\/\/doi.org\/10.1186\/s12967-021-02713-9.","journal-title":"J Transl Med"},{"key":"8582_CR40","doi-asserted-by":"publisher","DOI":"10.1002\/path.6443","author":"LE Vlaming-van Eijk","year":"2025","unstructured":"Vlaming-van Eijk LE, et al. Post-COVID-19 condition: clinical phenotypes, pathophysiological mechanisms, pathology, and management strategies. J Pathol. 2025. https:\/\/doi.org\/10.1002\/path.6443.","journal-title":"J Pathol"},{"key":"8582_CR41","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens13050388","author":"L Lupi","year":"2024","unstructured":"Lupi L, et al. The Potential Role of Viral Persistence in the Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). Pathogens. 2024. https:\/\/doi.org\/10.3390\/pathogens13050388.","journal-title":"Pathogens"},{"key":"8582_CR42","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adk3295","author":"MJ Peluso","year":"2024","unstructured":"Peluso MJ, et al. Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection. Sci Transl Med. 2024. https:\/\/doi.org\/10.1126\/scitranslmed.adk3295.","journal-title":"Sci Transl Med"},{"key":"8582_CR43","doi-asserted-by":"publisher","unstructured":"Whitcomb LA, Berry K, LaVergne SM, Natter N, Baxter BA, Rao S, Tipton M, Gritsenko MA, Weitz KK, Gerbasi V, Bramer LM, Piehowski PD, Webb TL, Henao-Tamayo M, Chicco AJ, Dunn J, Dutt TS, Ryan EP. Blood pro-thrombotic analytes and platelet activation are associated with post-acute sequelae of COVID-19. BMC Infect Dis. 2025 Dec;10. https:\/\/doi.org\/10.1186\/s12879-025-11824-3.","DOI":"10.1186\/s12879-025-11824-3"},{"key":"8582_CR44","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.bbi.2025.05.021","volume":"129","author":"CS Schreiber","year":"2025","unstructured":"Schreiber CS, Navarro Ramil L, Bieligk J, Meineke R, Rimmelzwaan G, K\u00e4ufer C, Richter F. Intravenous SARS-CoV-2 Spike protein induces neuroinflammation and alpha-Synuclein accumulation in brain regions relevant to Parkinson\u2019s disease. Brain Behav Immun. 2025;129:102\u201323. https:\/\/doi.org\/10.1016\/j.bbi.2025.05.021.","journal-title":"Brain Behav Immun"},{"key":"8582_CR45","doi-asserted-by":"publisher","unstructured":"Jiang Z, Shan T, Li Y, Han F, Feng B, Zhen X, Ni H, Peng J, Xu M. Persistent attenuation of lymphocyte subsets after mass SARS-CoV-2 Infection. Int J Infect Dis. 2025;108287. https:\/\/doi.org\/10.1016\/j.ijid.2025.108287.","DOI":"10.1016\/j.ijid.2025.108287"},{"key":"8582_CR46","doi-asserted-by":"publisher","DOI":"10.3390\/v15020400","author":"A Vojdani","year":"2023","unstructured":"Vojdani A, et al. Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID. Viruses. 2023. https:\/\/doi.org\/10.3390\/v15020400.","journal-title":"Viruses"},{"key":"8582_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2025.06.009","author":"EF Abu Shady","year":"2025","unstructured":"Abu Shady EF, et al. Epstein-Barr virus (EBV) reactivation in post COVID-19. Auris Nasus Larynx. 2025. https:\/\/doi.org\/10.1016\/j.anl.2025.06.009.","journal-title":"Auris Nasus Larynx"},{"key":"8582_CR48","doi-asserted-by":"publisher","unstructured":"Chien MH, Wang J, Lu KC, Lu CL. Herpes zoster reactivation following COVID-19 and the risk of renal, infectious, and autoimmune complications: a global propensity-matched cohort study. Biomedicines. 2025;13(7):1628. https:\/\/doi.org\/10.3390\/biomedicines13071628.","DOI":"10.3390\/biomedicines13071628"},{"issue":"28","key":"8582_CR49","doi-asserted-by":"publisher","first-page":"e2426564122","DOI":"10.1073\/pnas.2426564122","volume":"122","author":"V Shankar","year":"2025","unstructured":"Shankar V, Wilhelmy J, Curtis EJ, Michael B, Cervantes L, Mallajosyula V, Davis RW, Snyder M, Younis S, Robinson WH, Shankar S, Mischel PS, Bonilla H, Davis MM. Oxidative stress is a shared characteristic of ME\/CFS and Long COVID. Proc Natl Acad Sci U S A. 2025;122(28):e2426564122. https:\/\/doi.org\/10.1073\/pnas.2426564122.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8582_CR50","doi-asserted-by":"publisher","DOI":"10.1177\/11786469231220781","author":"M Taenzer","year":"2023","unstructured":"Taenzer M, et al. Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study. Int J Tryptophan Res. 2023. https:\/\/doi.org\/10.1177\/11786469231220781.","journal-title":"Int J Tryptophan Res"},{"key":"8582_CR51","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1186\/s12967-026-07684-3","volume":"24","author":"MC Garc\u00eda-Hidalgo","year":"2026","unstructured":"Garc\u00eda-Hidalgo MC, et al. Multilayer metabolomic integration reveals bioenergetic disruption in Long COVID. J Translational Med. 2026;24:237. https:\/\/doi.org\/10.1186\/s12967-026-07684-3.","journal-title":"J Translational Med"},{"issue":"1","key":"8582_CR52","doi-asserted-by":"publisher","first-page":"10552","DOI":"10.1038\/s41467-025-65597-z","volume":"16","author":"D Seo","year":"2025","unstructured":"Seo D, Choi Y, Jeong E, Bang S, Lee JS, Jang IH, Choi L, Kim JH, Shin W, Seo BR, Kim S, Jung HJ, Kim JY, Kim H, Lim YM, Kwon JS, Chang E, Lee J, Kam TI, Park SH, Lee EJ, Kim SH. Distinct brain alterations and neurodegenerative processes in cognitive impairment associated with post-acute sequelae of COVID-19. Nat Commun. 2025;16(1):10552. https:\/\/doi.org\/10.1038\/s41467-025-65597-z.","journal-title":"Nat Commun"},{"key":"8582_CR53","doi-asserted-by":"publisher","first-page":"103999","DOI":"10.1016\/j.ebiom.2022.103999","volume":"79","author":"C K\u00e4ufer","year":"2022","unstructured":"K\u00e4ufer C, Schreiber CS, Hartke AS, Denden I, Stanelle-Bertram S, Beck S, Kouassi NM, Beythien G, Becker K, Schreiner T, Schaumburg B, Beineke A, Baumg\u00e4rtner W, Gabriel G, Richter F. Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model. EBioMedicine. 2022;79:103999. https:\/\/doi.org\/10.1016\/j.ebiom.2022.103999.","journal-title":"EBioMedicine"},{"key":"8582_CR54","doi-asserted-by":"publisher","first-page":"105191","DOI":"10.1016\/j.ebiom.2024.105191","volume":"105","author":"CS Schreiber","year":"2024","unstructured":"Schreiber CS, Wiesweg I, Stanelle-Bertram S, Beck S, Kouassi NM, Schaumburg B, Gabriel G, Richter F, K\u00e4ufer C. Sex-specific biphasic alpha-synuclein response and alterations of interneurons in a COVID-19 hamster model. EBioMedicine. 2024;105:105191. https:\/\/doi.org\/10.1016\/j.ebiom.2024.105191.","journal-title":"EBioMedicine"},{"issue":"11","key":"8582_CR55","doi-asserted-by":"publisher","first-page":"102449","DOI":"10.1016\/j.xcrm.2025.102449","volume":"6","author":"S Shahbaz","year":"2025","unstructured":"Shahbaz S, Osman M, Syed H, Mason A, Rosychuk RJ, Cohen Tervaert JW, Elahi S. Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME\/CFS. Cell Rep Med. 2025;6(11):102449. https:\/\/doi.org\/10.1016\/j.xcrm.2025.102449.","journal-title":"Cell Rep Med"},{"key":"8582_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2025.101110","author":"AS Padhye","year":"2025","unstructured":"Padhye AS, et al. Blood diagnostic biomarkers for neurologic manifestations of long COVID. Brain Behav Immun - Health. 2025. https:\/\/doi.org\/10.1016\/j.bbih.2025.101110.","journal-title":"Brain Behav Immun - Health"},{"key":"8582_CR57","doi-asserted-by":"publisher","unstructured":"Bevan S, Javed H, Israel M, Primicheru L, Mumu M, Sun H, Maurer M, Oey O, Fedele L, Ribiero A, Serra J, Lang L, Birklein F, Dresel C, Chalabi J, Seibert F, Westhoff T, Wiemers L, Babel N, et al. Autoantibodies mediate pain and sensory dysfunction in post-COVID syndrome [Preprint]. Research Square. 2025. https:\/\/doi.org\/10.21203\/rs.3.rs-7989936\/v1.","DOI":"10.21203\/rs.3.rs-7989936\/v1"},{"key":"8582_CR58","doi-asserted-by":"publisher","DOI":"10.1101\/2025.11.20.689423","author":"M Mignolet","year":"2025","unstructured":"Mignolet M, Deroux C, Florkin T, Bielarz V, Swert KD, Halloin N, Sprimont L, Ladang A, George F, Gilloteaux J, Abeloos L, Weyenbergh JV, Jamoulle M, Diederich C, Gillet NA, Bulpa P, Nicaise C. Pathogenic IgG from long COVID patients with neurological sequelae triggers sensitive but not cognitive impairments upon transfer into mice. BioRxiv. 2025. https:\/\/doi.org\/10.1101\/2025.11.20.689423. Preprint.","journal-title":"BioRxiv"},{"key":"8582_CR59","doi-asserted-by":"publisher","DOI":"10.1101\/2025.12.01.691535","author":"BE Silva","year":"2025","unstructured":"Silva BE, dos Santos RS, Veras FP, Cilli EM, Olivier DdaS, de A. Belo MA, Charlie-Silva I, Caixeta ES, Barchuk AR, Nunes-Silva A, Romero TRL, Galdino G. SARS-CoV-2 Spike Peptides Trigger Nociceptive Responses Through Spinal TLR4 Pathways. BioRxiv. 2025. https:\/\/doi.org\/10.1101\/2025.12.01.691535. Preprint.","journal-title":"BioRxiv"},{"issue":"5","key":"8582_CR60","doi-asserted-by":"publisher","first-page":"106641","DOI":"10.1016\/j.jinf.2025.106641","volume":"91","author":"K Sano","year":"2025","unstructured":"Sano K, Kimura Y, Hirahata K, Kato H, Hasegawa H, Akutsu H, Ryo A, Goto A, Miyakawa K. SARS-CoV-2 spike-specific IgG4 class switching associates with clinical recovery in Long COVID. J Infect. 2025;91(5):106641. https:\/\/doi.org\/10.1016\/j.jinf.2025.106641.","journal-title":"J Infect"},{"key":"8582_CR61","doi-asserted-by":"publisher","unstructured":"Kwissa M, Mathayan M, Salunkhe SS, Bakthavachalam V, Ye Z, Sanborn MA, Condo S, Upadhye A, Nemakal A, Richner JM, Basu S, Novak RM, Jacobson JR, Ganesh BB, Cerda M, Utz PJ, Krishnan JA, Prabhakar BS, Rehman J. Persistent immune dysregulation during post-acute sequelae of COVID-19 is manifested in antibodies targeting envelope and nucleocapsid proteins [Preprint]. bioRxiv. 2025. https:\/\/doi.org\/10.1101\/2025.08.18.670908.","DOI":"10.1101\/2025.08.18.670908"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08582-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08582-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08582-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:02:05Z","timestamp":1783969325000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08582-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8582"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08582-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8764088\/v1","asserted-by":"object"}]},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]},"assertion":[{"value":"3 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics approval was obtained from the Ethics Committee of Hannover Medical School (reference number 11077_BO_K_2023). Furthermore, approval for the use of health insurance data according to \u00a7\u00a075 SGB X (Social Security Code Book 10) was given by the competent supervisory authority. The study was conducted in accordance with the principles of the Declaration of Helsinki. All potential participants were informed that their participation in the study was voluntary and that they had the right to refuse or withdraw at any time without any disadvantage. Participation in the study was based on electronic informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All the authors approved the final draft of the manuscript and are aware that this paper is being submitting to this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"892"}}