{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:21:36Z","timestamp":1787649696775,"version":"build-2736575974"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Ministry for Innovation and Technology, Hungary","award":["GINOP-2.3.2-15-2016-00043"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00043"]}]},{"name":"Ministry for Innovation and Technology, Hungary","award":["GINOP-2.3.2-15-2016-00050"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00050"]}]},{"name":"Ministry for Innovation and Technology, Hungary","award":["EFOP-3.6.2-16-2017-00006 LIVE LONGER"],"award-info":[{"award-number":["EFOP-3.6.2-16-2017-00006 LIVE LONGER"]}]},{"name":"National Research, Development and Innovation Office","award":["FK 128809"],"award-info":[{"award-number":["FK 128809"]}]},{"name":"National Research, Development and Innovation Office","award":["FK 135327"],"award-info":[{"award-number":["FK 135327"]}]},{"name":"National Research, Development and Innovation Office","award":["K123975"],"award-info":[{"award-number":["K123975"]}]},{"name":"National Research, Development and Innovation Office","award":["K 132623"],"award-info":[{"award-number":["K 132623"]}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"crossref","award":["POST-COVID2021-33"],"award-info":[{"award-number":["POST-COVID2021-33"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry for Innovation and Technology in Hungary","award":["TKP2020-IKA-04"],"award-info":[{"award-number":["TKP2020-IKA-04"]}]},{"name":"Ministry for Innovation and Technology in Hungary","award":["TKP2020-NKA-04"],"award-info":[{"award-number":["TKP2020-NKA-04"]}]},{"name":"Ministry for Innovation and Technology in Hungary","award":["TKP2021-EGA-19"],"award-info":[{"award-number":["TKP2021-EGA-19"]}]},{"name":"Ministry for Innovation and Technology in Hungary","award":["TKP2021-EGA-20"],"award-info":[{"award-number":["TKP2021-EGA-20"]}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"crossref","award":["BO\/00069\/21\/5"],"award-info":[{"award-number":["BO\/00069\/21\/5"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009232","name":"University of Debrecen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009232","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Severe cases of COVID-19 are characterized by an inflammatory burst, which is accompanied by multiorgan failure. The elderly population has higher risk for severe or fatal outcome for COVID-19. Inflammatory mediators facilitate the immune system to combat viral infection by producing antibodies against viral antigens. Several studies reported that the pro-inflammatory state and tissue damage in COVID-19 also promotes autoimmunity by autoantibody generation. We hypothesized that a subset of these autoantibodies targets cardiac antigens. Here we aimed to detect anti-cardiac autoantibodies in severe COVID-19 patients during hospitalization. For this purpose, 104 COVID-19 patients were recruited, while 40 heart failure patients with dilated cardiomyopathy and 20 patients with severe aortic stenosis served as controls. Patients were tested for anti-cardiac autoantibodies, using human heart homogenate as a bait. Follow-up samples were available in 29 COVID-19 patients. Anti-cardiac autoantibodies were detected in 68% (71 out of 104) of severe COVID-19 patients. Overall, 39% of COVID-19 patients had anti-cardiac IgG autoantibodies, while 51% had anti-cardiac autoantibodies of IgM isotype. Both IgG and IgM anti-cardiac autoantibodies were observed in 22% of cases, and multiple cardiac antigens were targeted in 38% of COVID-19 patients. These anti-cardiac autoantibodies targeted a diverse set of myocardial proteins, without apparent selectivity. As controls, heart failure patients (with dilated cardiomyopathy) had similar occurrence of IgG (45%, <jats:italic>p<\/jats:italic>\u2009=\u20090.57) autoantibodies, while significantly lower occurrence of IgM autoantibodies (30%, <jats:italic>p<\/jats:italic>\u2009=\u20090.03). Patients with advanced aortic stenosis had significantly lower number of both IgG (11%, <jats:italic>p<\/jats:italic>\u2009=\u20090.03) and IgM (10%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) type anti-cardiac autoantibodies than that in COVID-19 patients. Furthermore, we detected changes in the anti-cardiac autoantibody profile in 7 COVID-19 patients during hospital treatment. Surprisingly, the presence of these anti-cardiac autoantibodies did not affect the clinical outcome and the prevalence of the autoantibodies did not differ between the elderly (over 65\u00a0years) and the patients younger than 65\u00a0years of age. Our results demonstrate that the majority of hospitalized COVID-19 patients produce novel anti-cardiac IgM autoantibodies. COVID-19 also reactivates resident IgG autoantibodies. These autoantibodies may promote autoimmune reactions, which can complicate post-COVID recuperation, contributing to post-acute sequelae of COVID-19 (long COVID).<\/jats:p>","DOI":"10.1007\/s11357-022-00649-6","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T11:03:52Z","timestamp":1663326232000},"page":"2347-2360","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The majority of severe COVID-19 patients develop anti-cardiac autoantibodies"],"prefix":"10.1007","volume":"44","author":[{"given":"Mikl\u00f3s","family":"Fagyas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"B\u00e9la","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold P\u00e9ter","family":"R\u00e1duly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivetta Siket","family":"M\u00e1nyin\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilla","family":"M\u00e1rtha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Erd\u0151si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"S\u00e1ndor","family":"Sipka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enik\u0151","family":"Enyedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila \u00c1d\u00e1m","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia","family":"P\u00f3lik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Kappelmayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Borb\u00e9ly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Balla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Balla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"B\u00e1csi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-3653","authenticated-orcid":false,"given":"Attila","family":"T\u00f3th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"649_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s11357-020-00186-0","volume":"42","author":"J Nikolich-Zugich","year":"2020","unstructured":"Nikolich-Zugich J, Knox KS, Rios CT, et al. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. GeroScience. 2020;42:505\u201314. https:\/\/doi.org\/10.1007\/s11357-020-00186-0.","journal-title":"GeroScience"},{"key":"649_CR2","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s11739-020-02616-5","volume":"16","author":"A Krishnan","year":"2021","unstructured":"Krishnan A, Hamilton JP, Alqahtani SA, A. Woreta T,. A narrative review of coronavirus disease 2019 (COVID-19) clinical epidemiological characteristics and systemic manifestations. Intern Emerg Med. 2021;16:815\u201330. https:\/\/doi.org\/10.1007\/s11739-020-02616-5.","journal-title":"Intern Emerg Med"},{"key":"649_CR3","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.dsx.2021.04.007","volume":"15","author":"AV Raveendran","year":"2021","unstructured":"Raveendran AV, Jayadevan R, Sashidharan S. Diabetes & metabolic syndrome: clinical research & reviews long COVID: an overview. Diabetes Metab Syndr Clin Res Rev. 2021;15:869\u201375.","journal-title":"Diabetes Metab Syndr Clin Res Rev"},{"key":"649_CR4","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1001\/jama.2020.12603","volume":"324","author":"A Carf\u00ec","year":"2020","unstructured":"Carf\u00ec A, Bernabei R, Landi F, Group for the GAC-19 P-ACS. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324:603\u20135. https:\/\/doi.org\/10.1001\/jama.2020.12603.","journal-title":"JAMA"},{"key":"649_CR5","doi-asserted-by":"publisher","first-page":"993","DOI":"10.15585\/mmwr.mm6930e1","volume":"69","author":"MW Tenforde","year":"2020","unstructured":"Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom duration and risk factors for delayed return to usual health among [1] M. W. Tenforde et al., Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network \u2014 united. MMWR Morb Mortal Wkly Rep. 2020;69:993\u20138.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"649_CR6","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.15585\/mmwr.mm6940e1","volume":"69","author":"SB Morris","year":"2020","unstructured":"Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection \u2014 United Kingdom and United States. MMWR Morb Mortal Wkly Rep. 2020;69:1450\u20136. https:\/\/doi.org\/10.15585\/mmwr.mm6940e1.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"649_CR7","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1136\/annrheumdis-2020-218009","volume":"79","author":"PG Vlachoyiannopoulos","year":"2020","unstructured":"Vlachoyiannopoulos PG, Magira E, Alexopoulos H, et al. Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19. Ann Rheum Dis. 2020;79:1661\u20133.","journal-title":"Ann Rheum Dis"},{"key":"649_CR8","doi-asserted-by":"publisher","unstructured":"Bastard P, Rosen LB, Zhang Q, et al.\u00a0Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370. https:\/\/doi.org\/10.1126\/science.abd4585","DOI":"10.1126\/science.abd4585"},{"key":"649_CR9","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/s41586-021-03234-7","volume":"591","author":"AJ Combes","year":"2021","unstructured":"Combes AJ, Courau T, Kuhn NF, et al. Global absence and targeting of protective immune states in severe COVID-19. Nature. 2021;591:124\u201330. https:\/\/doi.org\/10.1038\/s41586-021-03234-7.","journal-title":"Nature"},{"key":"649_CR10","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41586-021-03631-y","volume":"595","author":"EY Wang","year":"2021","unstructured":"Wang EY, Mao T, Klein J, et al. Diverse functional autoantibodies in patients with COVID-19. Nature. 2021;595:283\u20138. https:\/\/doi.org\/10.1038\/s41586-021-03631-y.","journal-title":"Nature"},{"key":"649_CR11","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijid.2021.11.028","volume":"115","author":"M Fagyas","year":"2022","unstructured":"Fagyas M, Fejes Z, S\u00fct\u0151 R, et al. Circulating ACE2 activity predicts mortality and disease severity in hospitalized COVID-19 patients. Int J Infect Dis. 2022;115:8\u201316. https:\/\/doi.org\/10.1016\/j.ijid.2021.11.028.","journal-title":"Int J Infect Dis"},{"key":"649_CR12","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1007\/s11357-021-00467-2","volume":"43","author":"M Fagyas","year":"2021","unstructured":"Fagyas M, B\u00e1nhegyi V, \u00dari K, et al. Changes in the SARS-CoV-2 cellular receptor ACE2 levels in cardiovascular patients: a potential biomarker for the stratification of COVID-19 patients. 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BMC Bioinformatics. 2017;18:529. https:\/\/doi.org\/10.1186\/s12859-017-1934-z.","journal-title":"BMC Bioinformatics"},{"key":"649_CR15","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1590\/0037-8682-0147-2020","volume":"53","author":"BC Muniz","year":"2020","unstructured":"Muniz BC, Milito MA, Marchiori E. COVID-19-computed tomography findings in two patients in Petr\u00f3polis, Rio de Janeiro, Brazil. Rev Soc Bras Med Trop. 2020;53:3\u20134. https:\/\/doi.org\/10.1590\/0037-8682-0147-2020.","journal-title":"Rev Soc Bras Med Trop"},{"key":"649_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2020.587517","volume":"11","author":"D Gagiannis","year":"2020","unstructured":"Gagiannis D, Steinestel J, Hackenbroch C, et al. Clinical, serological, and histopathological similarities between severe COVID-19 and acute exacerbation of connective tissue disease-associated interstitial lung disease (CTD-ILD). Front Immunol. 2020;11:1\u201311. https:\/\/doi.org\/10.3389\/fimmu.2020.587517.","journal-title":"Front Immunol"},{"key":"649_CR17","doi-asserted-by":"publisher","unstructured":"Su Y, Yuan D, Chen DG, et al.\u00a0Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2020. https:\/\/doi.org\/10.1016\/j.cell.2022.01.014","DOI":"10.1016\/j.cell.2022.01.014"},{"key":"649_CR18","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s00392-020-01626-9","volume":"109","author":"B Li","year":"2020","unstructured":"Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;109:531\u20138. https:\/\/doi.org\/10.1007\/s00392-020-01626-9.","journal-title":"Clin Res Cardiol"},{"key":"649_CR19","doi-asserted-by":"publisher","first-page":"100025","DOI":"10.1016\/j.ahjo.2021.100025","volume":"5","author":"NM Dixit","year":"2021","unstructured":"Dixit NM, Churchill A, Nsair A, Hsu JJ. Post-acute COVID-19 syndrome and the cardiovascular system: what is known? Am Hear J Plus Cardiol Res Pract. 2021;5:100025. https:\/\/doi.org\/10.1016\/j.ahjo.2021.100025.","journal-title":"Am Hear J Plus Cardiol Res Pract"},{"key":"649_CR20","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1080\/08916930701619235","volume":"41","author":"ALP Caforio","year":"2008","unstructured":"Caforio ALP, Tona F, Bottaro S, et al. Clinical implications of anti-heart autoantibodies in myocarditis and dilated cardiomyopathy. Autoimmunity. 2008;41:35\u201345. https:\/\/doi.org\/10.1080\/08916930701619235.","journal-title":"Autoimmunity"},{"key":"649_CR21","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1016\/j.hrthm.2011.06.032","volume":"8","author":"H-C Lee","year":"2011","unstructured":"Lee H-C, Huang KTL, Wang X-L, Shen W-K. Autoantibodies and cardiac arrhythmias. Hear Rhythm. 2011;8:1788\u201395. https:\/\/doi.org\/10.1016\/j.hrthm.2011.06.032.","journal-title":"Hear Rhythm"},{"key":"649_CR22","doi-asserted-by":"publisher","first-page":"5417","DOI":"10.1038\/s41467-021-25509-3","volume":"12","author":"SE Chang","year":"2021","unstructured":"Chang SE, Feng A, Meng W, et al. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat Commun. 2021;12:5417. https:\/\/doi.org\/10.1038\/s41467-021-25509-3.","journal-title":"Nat Commun"},{"key":"649_CR23","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.cell.2020.09.034","volume":"183","author":"CN Gruber","year":"2020","unstructured":"Gruber CN, Patel RS, Trachtman R, et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell. 2020;183:982-995.e14. https:\/\/doi.org\/10.1016\/j.cell.2020.09.034.","journal-title":"Cell"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-022-00649-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-022-00649-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-022-00649-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T02:14:23Z","timestamp":1671588863000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-022-00649-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["649"],"URL":"https:\/\/doi.org\/10.1007\/s11357-022-00649-6","relation":{},"ISSN":["2509-2715","2509-2723"],"issn-type":[{"value":"2509-2715","type":"print"},{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]},"assertion":[{"value":"27 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}