{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T22:21:48Z","timestamp":1778538108251,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Post-COVID-19 syndrome (PCS), characterized by persistent fatigue, can develop after a SARS-CoV-2 infection. Myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS) is a chronic, post-infectious condition marked by severe fatigue and post-exertional malaise. This study aimed to determine the incidence and characteristics of PCS and ME\/CFS in a cohort of hospital employees (HEs) with SARS-CoV-2 infections. Materials and Methods: All HEs who tested SARS-CoV-2-positive between March 2020 and May 2021 who later reported persistent fatigue were invited for an assessment from July to December 2022. Canadian Consensus Criteria were used for the diagnosis of ME\/CFS. Assessments included the Montreal Cognitive Assessment (MoCA), and determination of coagulation factors, Epstein\u2013Barr virus (EBV) antibodies and autoantibodies (AABs) against G-protein-coupled receptors (GPCRs). Results: Of the 221 HEs, 11.8% (95% confidence interval (CI95%) 7.8\u201316.8, 26\/221) still reported persistent fatigue and 3.2% (CI95% 1.3\u20136.4, 7\/221) were diagnosed with ME\/CFS. In total, 19 HEs (median age 51.0 years, 89.4% female, 63.1% possible or confirmed nosocomial infection) participated in our assessment. In 42.1% (8\/19) MoCA results were below normal. Laboratory values showed increased GPCR AABs in 66.6% (12\/18), possible EBV reactivation in 86.7% (13\/15) and coagulation parameters suggesting inflammatory processes in 38.9% (7\/18). Conclusions: Our study was able to determine lower-bound incidences of PCS with fatigue and ME\/CFS and demonstrated a diagnostic pathway for HEs following SARS-CoV-2 infections. Possible EBV reactivation, increased GPCR AABs and potential coagulation cascade activation may play a pathogenic role.<\/jats:p>","DOI":"10.3390\/medicina62030480","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T08:51:33Z","timestamp":1772614293000},"page":"480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment and Incidence Determination of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome Following a SARS-CoV-2 Infection in a Prospective Cohort of Hospital Employees"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0960-3983","authenticated-orcid":false,"given":"Matthias","family":"Tack","sequence":"first","affiliation":[{"name":"Institute of Hygiene, Cologne Merheim Medical Center, University of Witten\/Herdecke, Ostmerheimerstra\u00dfe 200, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalie","family":"Gruber","sequence":"additional","affiliation":[{"name":"Institute of Hygiene, Cologne Merheim Medical Center, University of Witten\/Herdecke, Ostmerheimerstra\u00dfe 200, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3470-5600","authenticated-orcid":false,"given":"Leia","family":"Betting","sequence":"additional","affiliation":[{"name":"Statistical Consulting and Analysis, Center for Higher Education, TU Dortmund University, Vogelpothsweg 78, 44227 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4350-0748","authenticated-orcid":false,"given":"Swetlana","family":"Herbrandt","sequence":"additional","affiliation":[{"name":"Statistical Consulting and Analysis, Center for Higher Education, TU Dortmund University, Vogelpothsweg 78, 44227 Dortmund, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuling","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Cologne Merheim Medical Center, Ostmerheimerstra\u00dfe 200, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Schl\u00f6\u00dfer","sequence":"additional","affiliation":[{"name":"Institute of Transfusion Medicine, Cologne Merheim Medical Center, Ostmerheimerstra\u00dfe 200, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"H\u00e4ussermann","sequence":"additional","affiliation":[{"name":"Department of Geriatric Psychiatry and Psychotherapy, LVR Hospital Cologne, Wilhelm-Griesinger-Stra\u00dfe 23, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Maegele","sequence":"additional","affiliation":[{"name":"Department of Traumatology and Orthopedic Surgery, Cologne Merheim Medical Center, Institute for Research in Operative Medicine (IFOM), University of Witten\/Herdecke, Ostmerheimerstra\u00dfe 200, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerlinde","family":"Schlang","sequence":"additional","affiliation":[{"name":"Department of Occupational Medicine, Cologne Merheim Medical Center, Ostmerheimerstra\u00dfe 200, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2268-6310","authenticated-orcid":false,"given":"Frauke","family":"Mattner","sequence":"additional","affiliation":[{"name":"Institute of Hygiene, Cologne Merheim Medical Center, University of Witten\/Herdecke, Ostmerheimerstra\u00dfe 200, 51109 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, April 04). WHO COVID-19 Dashboard. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bbi.2021.12.020","article-title":"Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis","volume":"101","author":"Ceban","year":"2022","journal-title":"Brain. Behav. Immun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/S0140-6736(22)01214-4","article-title":"Persistence of somatic symptoms after COVID-19 in The Netherlands: An observational cohort study","volume":"400","author":"Ballering","year":"2022","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41579-022-00846-2","article-title":"Long COVID: Major findings, mechanisms and recommendations","volume":"21","author":"Davis","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S0140-6736(24)01136-X","article-title":"Long COVID: A clinical update","volume":"404","author":"Greenhalgh","year":"2024","journal-title":"Lancet"},{"key":"ref_6","unstructured":"World Health Organization (2021). A Clinical Case Definition of Post COVID-19 Condition by a Delphi Consensus, World Health Organization."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Peter, R.S., Nieters, A., Kr\u00e4usslich, H.-G., Brockmann, S.O., G\u00f6pel, S., Kindle, G., Merle, U., Steinacker, J.M., Rothenbacher, D., and Kern, W.V. (2022). Post-acute sequelae of COVID-19 six to 12 months after infection: Population based study. BMJ, 379.","DOI":"10.1136\/bmj-2022-071050"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Steiner, S., Fehrer, A., Hoheisel, F., Schoening, S., Aschenbrenner, A., Babel, N., Bellmann-Strobl, J., Finke, C., Fluge, O., and Froehlich, L. (2023). Understanding, diagnosing, and treating Myalgic encephalomyelitis\/chronic fatigue syndrome\u2014State of the art: Report of the 2nd international meeting at the Charite Fatigue Center. Autoimmun. Rev., 22.","DOI":"10.1016\/j.autrev.2023.103452"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00508-024-02372-y","article-title":"Interdisziplin\u00e4res, kollaboratives D-A-CH Konsensus-Statement zur Diagnostik und Behandlung von Myalgischer Enzephalomyelitis\/Chronischem Fatigue-Syndrom","volume":"136","author":"Hoffmann","year":"2024","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12967-020-02269-0","article-title":"Systematic review and meta-analysis of the prevalence of chronic fatigue syndrome\/myalgic encephalomyelitis (CFS\/ME)","volume":"18","author":"Lim","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nacul, L., Authier, F.J., Scheibenbogen, C., Lorusso, L., Helland, I.B., Martin, J.A., Sirbu, C.A., Mengshoel, A.M., Polo, O., and Behrends, U. (2021). European Network on Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME\/CFS in Europe. Medicina, 57.","DOI":"10.3390\/medicina57050510"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cotler, J., Holtzman, C., Dudun, C., and Jason, L. (2018). A Brief Questionnaire to Assess Post-Exertional Malaise. Diagnostics, 8.","DOI":"10.3390\/diagnostics8030066"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/joim.13792","article-title":"Epigenetic reprograming in myalgic encephalomyelitis\/chronic fatigue syndrome: A narrative of latent viruses","volume":"296","author":"Apostolou","year":"2024","journal-title":"J. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.autrev.2018.01.009","article-title":"Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome\u2014Evidence for an autoimmune disease","volume":"17","author":"Sotzny","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5104","DOI":"10.1038\/s41467-022-32507-6","article-title":"A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity","volume":"13","author":"Kedor","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Legler, F., Meyer-Arndt, L., M\u00f6dl, L., Kedor, C., Freitag, H., Stein, E., Hoppmann, U., Rust, R., Wittke, K., and Siebert, N. (2023). Long-term symptom severity and clinical biomarkers in post-COVID-19\/chronic fatigue syndrome: Results from a prospective observational cohort. eClinicalMedicine, 63.","DOI":"10.1016\/j.eclinm.2023.102146"},{"key":"ref_17","first-page":"830","article-title":"Post-COVID-Syndrom mit Fatigue und Belastungsintoleranz: Myalgische Enzephalomyelitis bzw. Chronisches Fatigue-Syndrom","volume":"63","author":"Scheibenbogen","year":"2022","journal-title":"Inn. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gruber, R., Montilva Ludewig, M.V., We\u00dfels, C., Schlang, G., Jedhoff, S., Herbrandt, S., and Mattner, F. (2024). Long-term symptoms after SARS-CoV-2 infection in a cohort of hospital employees: Duration and predictive factors. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-023-08710-1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"61","author":"Altman","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Westerlind, E., Palstam, A., Sunnerhagen, K.S., and Persson, H.C. (2021). Patterns and predictors of sick leave after COVID-19 and long Covid in a national Swedish cohort. BMC Public Health, 21.","DOI":"10.1186\/s12889-021-11013-2"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Augustin, M., Schommers, P., Stecher, M., Dewald, F., Gieselmann, L., Gruell, H., Horn, C., Vanshylla, K., Cristanziano, V.D., and Osebold, L. (2021). Post-COVID syndrome in non-hospitalised patients with COVID-19: A longitudinal prospective cohort study. Lancet Reg. Health\u2014Eur., 6.","DOI":"10.1016\/j.lanepe.2021.100122"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2147\/POR.S316186","article-title":"Risk Predictors and Symptom Features of Long COVID Within a Broad Primary Care Patient Population Including Both Tested and Untested Patients","volume":"12","author":"Jones","year":"2021","journal-title":"Pragmatic Obs. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Katsoularis, I., Fonseca-Rodriguez, O., Farrington, P., Jerndal, H., Lundevaller, E.H., Sund, M., Lindmark, K., and Fors Connolly, A.M. (2022). Risks of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19: Nationwide self-controlled cases series and matched cohort study. BMJ, 377.","DOI":"10.1136\/bmj-2021-069590"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e14251","DOI":"10.1111\/nmo.14251","article-title":"Prevalence and risk factors for gastrointestinal symptoms after recovery from COVID-19","volume":"34","author":"Blackett","year":"2022","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1300\/J092v11n01_02","article-title":"Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Clinical Working Case Definition, diagnostic and treatment protocols","volume":"11","author":"Carruthers","year":"2003","journal-title":"J. Chronic Fatigue Syndr."},{"key":"ref_26","unstructured":"Charit\u00e9 Fatigue Centrum (2022, March 21). Kanadische Kriterien f\u00fcr die Diagnose CFS\/ME; Bell-Score. Available online: https:\/\/www.privatpraxis-kosttor.de\/wp-content\/uploads\/2022\/08\/kanadische-kriterien-bell-score-cfs-mit-auswertung.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bell, D.S. (1995). The Doctor\u2019s Guide to Chronic Fatigue Syndrome, Da Capo Press Inc.","DOI":"10.1300\/J092v01n01_03"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s10286-019-00619-7","article-title":"The Schellong test: Detecting orthostatic blood pressure and heart rate changes in German-speaking countries","volume":"29","author":"Fanciulli","year":"2019","journal-title":"Clin. Auton. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10286-011-0119-5","article-title":"Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome","volume":"21","author":"Freeman","year":"2011","journal-title":"Clin. Auton. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1093\/eurheartj\/ehy037","article-title":"2018 ESC Guidelines for the diagnosis and management of syncope","volume":"39","author":"Brignole","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Levine, T.D. (2018). Small Fiber Neuropathy: Disease Classification Beyond Pain and Burning. J. Cent. Nerv. Syst. Dis., 10.","DOI":"10.1177\/1179573518771703"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Malecki, M., Luesebrink, J., Wendel, A.F., and Mattner, F. (2021). Analysis of external quality assessment samples revealed crucial performance differences between commercial RT-PCR assays for SARS-CoV-2 detection when taking extraction methods and real-time-PCR instruments into account. J. Virol. Methods, 295.","DOI":"10.1016\/j.jviromet.2021.114202"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Laubscher, G.J., Lourens, P.J., Venter, C., Kell, D.B., and Pretorius, E. (2021). TEG, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy. J. Clin. Med., 10.","DOI":"10.3390\/jcm10225381"},{"key":"ref_35","unstructured":"R Core Team (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_36","unstructured":"World Health Organization (2024, November 04). Living Guidance for Clinical Management of COVID-19. Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-clinical-2021-2."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/s41591-022-01840-0","article-title":"Long COVID after breakthrough SARS-CoV-2 infection","volume":"28","author":"Bowe","year":"2022","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s13365-021-00949-1","article-title":"Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19","volume":"27","author":"Simani","year":"2021","journal-title":"J. Neurovirol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Unger, E.R., Lin, J.-M.S., Wisk, L.E., Yu, H., L\u2019Hommedieu, M., Lavretsky, H., Montoy, J.C.C., Gottlieb, M.A., Rising, K.L., and Gentile, N.L. (2024). Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome After SARS-CoV-2 Infection. JAMA Netw. Open, 7.","DOI":"10.1001\/jamanetworkopen.2024.23555"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s11606-024-09290-9","article-title":"Incidence and Prevalence of Post-COVID-19 Myalgic Encephalomyelitis: A Report from the Observational RECOVER-Adult Study","volume":"40","author":"Vernon","year":"2025","journal-title":"J. Gen. Intern. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Donadio, V., Incensi, A., Furia, A., Parisini, S., Colaci, F., Giannoccaro, M.P., Morelli, L., Ricciardiello, F., Di Stasi, V., and De Maria, A. (2025). Small fiber neuropathy associated with COVID-19 infection and vaccination: A prospective case\u2013control study. Eur. J. Neurol., 32.","DOI":"10.1111\/ene.16538"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.bbi.2023.11.028","article-title":"Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment","volume":"116","author":"Besteher","year":"2024","journal-title":"Brain. Behav. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1186\/s12933-022-01623-4","article-title":"Proteomics of fibrin amyloid microclots in long COVID\/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system","volume":"21","author":"Kruger","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbi.2015.09.013","article-title":"Antibodies to beta adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome","volume":"52","author":"Loebel","year":"2016","journal-title":"Brain. Behav. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.clnesp.2024.11.023","article-title":"Decreased levels of vitamin D in Post-Corona Virus-19 Disease syndrome (PCS) patients compared to a control group","volume":"65","author":"Braunlich","year":"2025","journal-title":"Clin. Nutr. 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