{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:49:57Z","timestamp":1779083397606,"version":"3.51.4"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"else-kr\u00f6ner-fresenius foundation"},{"DOI":"10.13039\/501100017268","name":"berlin institute of health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100017268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010447","name":"dzhk","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"crossref"}]},{"name":"bmbf"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Aims and methods<\/jats:title>\n<jats:p>We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1\u03b2 antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41\u00b15%; 1\/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154\u00b143 U\/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca<jats:sup>2+<\/jats:sup> transient amplitudes and altered baseline [Ca<jats:sup>2+<\/jats:sup>] upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca<jats:sup>2+<\/jats:sup> release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca<jats:sup>2+<\/jats:sup> release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca<jats:sup>2+<\/jats:sup> release or Ca<jats:sup>2+<\/jats:sup> signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca<jats:sup>2+<\/jats:sup> signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca<jats:sup>2+<\/jats:sup> imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0255976","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T18:47:29Z","timestamp":1629398849000},"page":"e0255976","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["COVID19-associated cardiomyocyte dysfunction, arrhythmias and the effect of Canakinumab"],"prefix":"10.1371","volume":"16","author":[{"given":"Sanzio","family":"Dimai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Semmler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashok","family":"Prabhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-4605","authenticated-orcid":true,"given":"Harald","family":"Stachelscheid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Huettemeister","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra C.","family":"Klaucke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Lacour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Blaschke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Kruse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul","family":"Parwani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif-Hendrik","family":"Boldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Bullinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkert M.","family":"Pieske","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank R.","family":"Heinzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-4615","authenticated-orcid":true,"given":"Felix","family":"Hohendanner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"pone.0255976.ref001","article-title":"Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan","author":"S Shi","year":"2020","journal-title":"China. 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