{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:50:12Z","timestamp":1777657812197,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010118","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000}}],"reference-count":72,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009396","name":"Universit\u00e4tsSpital Z\u00fcrich","doi-asserted-by":"publisher","award":["Innovation Fund (INNOV00096)"],"award-info":[{"award-number":["Innovation Fund (INNOV00096)"]}],"id":[{"id":"10.13039\/501100009396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009396","name":"Universit\u00e4tsSpital Z\u00fcrich","doi-asserted-by":"publisher","award":["Innovation Fund (INNOV00096)"],"award-info":[{"award-number":["Innovation Fund (INNOV00096)"]}],"id":[{"id":"10.13039\/501100009396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006447","name":"Universit\u00e4t Z\u00fcrich","doi-asserted-by":"publisher","award":["Institutional core funding"],"award-info":[{"award-number":["Institutional core funding"]}],"id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009396","name":"Universit\u00e4tsSpital Z\u00fcrich","doi-asserted-by":"publisher","award":["Institutional core funding"],"award-info":[{"award-number":["Institutional core funding"]}],"id":[{"id":"10.13039\/501100009396","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss Personalized Health Network","award":["Driver Grant 2017DRI17"],"award-info":[{"award-number":["Driver Grant 2017DRI17"]}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC Prion2020, 670958"],"award-info":[{"award-number":["ERC Prion2020, 670958"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008483","name":"NOMIS Stiftung","doi-asserted-by":"publisher","award":["Distinguished Scientist Award"],"award-info":[{"award-number":["Distinguished Scientist Award"]}],"id":[{"id":"10.13039\/501100008483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity in targeting phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and\/or aPL against cardiolipin and\/or \u03b22-glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by\u2013among other factors\u2013viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL with prothrombin (PT). The strength of the antibody response against SARS-CoV-2 was further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity, and aPL against PT in patients with SARS-CoV-2.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010118","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T13:28:47Z","timestamp":1638538127000},"page":"e1010118","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6073-8811","authenticated-orcid":true,"given":"Marc","family":"Emmenegger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-6474","authenticated-orcid":true,"given":"Sreedhar Saseendran","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishalini","family":"Emmenegger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-5529","authenticated-orcid":true,"given":"Tomas","family":"Malinauskas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Buettner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Rose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Schierack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin F.","family":"Sprinzl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens J.","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl J.","family":"Lackner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriano","family":"Aguzzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6861-6827","authenticated-orcid":true,"given":"Dirk","family":"Roggenbuck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1372-3297","authenticated-orcid":true,"given":"Katrin B. M.","family":"Frauenknecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"ppat.1010118.ref001","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.abd4585","article-title":"Autoantibodies against type I IFNs in patients with life-threatening COVID-19","volume":"370","author":"P Bastard","year":"2020","journal-title":"Science (80-)."},{"key":"ppat.1010118.ref002","article-title":"Clinically identifiable autoreactivity is common in severe SARS-CoV-2 infection","author":"MC Woodruff","year":"2020","journal-title":"medRxiv"},{"key":"ppat.1010118.ref003","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/cts.12805","article-title":"Clinical and Autoimmune Characteristics of Severe and Critical Cases of COVID-19","volume":"13","author":"Y Zhou","year":"2020","journal-title":"Clin Transl 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A solution to dependency: Using multilevel analysis to accommodate nested data","volume":"17","author":"E Aarts","year":"2014","journal-title":"Nat Neurosci"},{"key":"ppat.1010118.ref033","volume-title":"Applied Mixed Models in Medicine.","author":"H Brown","year":"2015","edition":"3"},{"key":"ppat.1010118.ref034","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fpsyg.2015.00002","article-title":"Linear mixed-effects models for within-participant psychology experiments: an introductory tutorial and free, graphical user interface (LMMgui).","volume":"0","author":"DA Magezi","year":"2015","journal-title":"Front Psychol"},{"key":"ppat.1010118.ref035","doi-asserted-by":"crossref","first-page":"6071","DOI":"10.1074\/jbc.M115.700401","article-title":"How the Linker Connecting the Two Kringles Influences Activation and Conformational Plasticity of Prothrombin","volume":"291","author":"N Pozzi","year":"2016","journal-title":"J Biol Chem"},{"key":"ppat.1010118.ref036","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.chom.2020.06.010","article-title":"Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike","volume":"28","author":"J Huo","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ppat.1010118.ref037","doi-asserted-by":"crossref","first-page":"e575","DOI":"10.1016\/S2352-3026(20)30216-7","article-title":"Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study","volume":"7","author":"G Goshua","year":"2020","journal-title":"Lancet Haematol"},{"key":"ppat.1010118.ref038","first-page":"1","article-title":"The unique characteristics of COVID-19 coagulopathy","volume":"24","author":"T Iba","year":"2020","journal-title":"Crit Care"},{"key":"ppat.1010118.ref039","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3390\/jcm10020191","article-title":"Proposal of the Definition for COVID-19-Associated Coagulopathy","volume":"10","author":"T Iba","year":"2021","journal-title":"J Clin Med"},{"key":"ppat.1010118.ref040","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Z Varga","year":"2020","journal-title":"Lancet"},{"key":"ppat.1010118.ref041","first-page":"63","article-title":"SARS-CoV-2 leads to a small vessel endotheliitis in the heart","author":"U Maccio","year":"2021","journal-title":"EBioMedicine"},{"key":"ppat.1010118.ref042","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jaut.2009.02.008","article-title":"Catastrophic antiphospholipid syndrome (CAPS): Descriptive analysis of a series of 280 patients from the \u201cCAPS Registry.\u201d","volume":"32","author":"R Cervera","year":"2009","journal-title":"J Autoimmun"},{"key":"ppat.1010118.ref043","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1177\/096120339400300417","article-title":"\u2018Primary\u2019, \u2018Secondary\u2019 and Other Variants of the Antiphospholipid Syndrome","volume":"3","author":"RA Asherson","year":"1994","journal-title":"Lupus"},{"key":"ppat.1010118.ref044","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11926-009-0073-6","article-title":"Update on the Diagnosis, Treatment, and Prognosis of the Catastrophic Antiphospholipid Syndrome","volume":"12","author":"R. Cervera","year":"2010","journal-title":"Curr Rheumatol Rep."},{"key":"ppat.1010118.ref045","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1111\/jth.14994","article-title":"Antiphospholipid antibodies in patients with COVID-19: A relevant observation?","volume":"18","author":"K Devreese","year":"2020","journal-title":"J Thromb Haemost"},{"key":"ppat.1010118.ref046","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1111\/jth.14867","article-title":"Lupus anticoagulant is frequent in patients with Covid-19","volume":"18","author":"I Harzallah","year":"2020","journal-title":"J Thromb Haemost"},{"key":"ppat.1010118.ref047","first-page":"754","article-title":"Frequency and clinical correlates of antiphospholipid antibodies arising in patients with SARS-CoV-2 infection: Findings from a multicentre study on 122 cases","volume":"38","author":"M Gatto","year":"2020","journal-title":"Clin Exp 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Xiao","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"ppat.1010118.ref055","first-page":"1","article-title":"Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies","author":"A Cristiano","year":"2021","journal-title":"Clin Rheumatol."},{"key":"ppat.1010118.ref056","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s10495-006-0581-z","article-title":"Identification of poly-reactive natural IgM antibody that recognizes late apoptotic cells and promotes phagocytosis of the cells","volume":"12","author":"M Fu","year":"2007","journal-title":"Apoptosis"},{"key":"ppat.1010118.ref057","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1084\/jem.153.3.694","article-title":"Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 Streptococcus pneumoniae","volume":"153","author":"DE Briles","year":"1981","journal-title":"J Exp Med"},{"key":"ppat.1010118.ref058","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-017-0894-6","article-title":"Natural IgM antibodies that bind neoepitopes exposed as a result of spinal cord injury, drive secondary injury by activating complement","volume":"14","author":"A Narang","year":"2017","journal-title":"J Neuroinflammation"},{"key":"ppat.1010118.ref059","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-020-00334-0","article-title":"SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation.","volume":"5","author":"S Li","year":"2020","journal-title":"Signal Transduct Target Ther"},{"key":"ppat.1010118.ref060","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1165\/rcmb.2016-0011PS","article-title":"Surfactant lipids at the host-environment interface metabolic sensors, suppressors, and effectors of inflammatory lung disease","volume":"54","author":"MB Fessler","year":"2016","journal-title":"Am J 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