{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:02:18Z","timestamp":1781712138530,"version":"3.54.5"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2021,1,19]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A\/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Male sex was more common in the COVID-19 group (\n              <jats:italic>P<\/jats:italic>\n              =0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (\n              <jats:italic>P<\/jats:italic>\n              =0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (\n              <jats:italic>P<\/jats:italic>\n              =0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (\n              <jats:italic>P<\/jats:italic>\n              =0.69,\n              <jats:italic>P<\/jats:italic>\n              =1.00,\n              <jats:italic>P<\/jats:italic>\n              =0.46,\n              <jats:italic>P<\/jats:italic>\n              =0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.120.050754","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T21:15:22Z","timestamp":1605561322000},"page":"230-243","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":153,"title":["COVID-19\u2013Associated Nonocclusive Fibrin Microthrombi in the Heart"],"prefix":"10.1161","volume":"143","author":[{"given":"Melanie C.","family":"Bois","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Boire","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Layman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Aubry","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam P.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja C.","family":"Roden","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reade A.","family":"Quinton","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Larsen","sequence":"additional","affiliation":[{"name":"Arkana Laboratories, Little Rock (C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young","family":"Erben","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Mayo Clinic, Jacksonville, FL (Y.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramanath","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology (M.C.B., N.A.B., A.J.L., M.-C.A., M.P.A., A.C.R., C.E.H., R.A.Q., R.M., B.R.K., P.T.L., J.J.M.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Division of Biomedical Statistics and Informatics (S.M.J.), Mayo Clinic, Rochester, 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