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  1. Article ; Online: Microthrombi cause cardiac injury in COVID-19.

    Fernández-Ruiz, Irene

    Nature reviews. Cardiology

    2021  Volume 18, Issue 5, Page(s) 306

    MeSH term(s) COVID-19 ; Humans ; SARS-CoV-2 ; Thrombosis
    Language English
    Publishing date 2021-02-04
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2490375-9
    ISSN 1759-5010 ; 1759-5002
    ISSN (online) 1759-5010
    ISSN 1759-5002
    DOI 10.1038/s41569-021-00524-5
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  2. Article ; Online: Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study.

    Pellegrini, Dario / Kawakami, Rika / Guagliumi, Giulio / Sakamoto, Atsushi / Kawai, Kenji / Gianatti, Andrea / Nasr, Ahmed / Kutys, Robert / Guo, Liang / Cornelissen, Anne / Faggi, Lara / Mori, Masayuki / Sato, Yu / Pescetelli, Irene / Brivio, Matteo / Romero, Maria / Virmani, Renu / Finn, Aloke V

    Circulation

    2021  Volume 143, Issue 10, Page(s) 1031–1042

    Abstract: ... strategies may be useful to counteract the cardiac effects of COVID-19 infection. ... 2019 (COVID-19) and portends poorer prognosis. However, the mechanism and the type of myocardial damage ... We conducted a systematic pathological analysis of 40 hearts from hospitalized patients dying of COVID-19 ...

    Abstract Background: Cardiac injury is common in patients who are hospitalized with coronavirus disease 2019 (COVID-19) and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain uncertain.
    Methods: We conducted a systematic pathological analysis of 40 hearts from hospitalized patients dying of COVID-19 in Bergamo, Italy, to determine the pathological mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury.
    Results: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Compared with subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and have shorter symptom onset to admission. The incidence of severe coronary artery disease (ie, >75% cross-sectional narrowing) was not significantly different between those with and without necrosis. Three of 14 (21.4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction, defined as ≥1 cm
    Conclusions: The most common pathological cause of myocyte necrosis was microthrombi. Microthrombi were different in composition from intramyocardial thromboemboli from COVID-19-negative subjects and from coronary thrombi retrieved from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. Tailored antithrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.
    MeSH term(s) Aged ; COVID-19/pathology ; COVID-19/virology ; Coronary Thrombosis/etiology ; Coronary Thrombosis/pathology ; Coronary Thrombosis/virology ; Coronary Vessels/pathology ; Coronary Vessels/virology ; Female ; Heart/virology ; Humans ; Italy ; Male ; Middle Aged ; Myocardial Infarction/pathology ; Myocardial Infarction/virology ; Myocardium/pathology ; SARS-CoV-2 ; ST Elevation Myocardial Infarction/epidemiology ; ST Elevation Myocardial Infarction/virology
    Language English
    Publishing date 2021-01-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.120.051828
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  3. Article ; Online: Letter by Wong and Siu Regarding Article, "Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study".

    Wong, Chun-Ka / Siu, Chung-Wah

    Circulation

    2021  Volume 144, Issue 7, Page(s) e156–e157

    MeSH term(s) COVID-19 ; Heart Injuries/etiology ; Humans ; SARS-CoV-2 ; Thrombosis
    Language English
    Publishing date 2021-08-16
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.121.054509
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  4. Article ; Online: Response by Pellegrini et al to Letter Regarding Article, "Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study".

    Pellegrini, Dario / Guagliumi, Giulio / Finn, Aloke V

    Circulation

    2021  Volume 144, Issue 7, Page(s) e158–e159

    MeSH term(s) COVID-19 ; Heart Injuries ; Humans ; SARS-CoV-2 ; Thrombosis
    Language English
    Publishing date 2021-08-16
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.121.055585
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  5. Article ; Online: COVID-19-Associated Nonocclusive Fibrin Microthrombi in the Heart.

    Bois, Melanie C / Boire, Nicholas A / Layman, Andrew J / Aubry, Marie-Christine / Alexander, Mariam P / Roden, Anja C / Hagen, Catherine E / Quinton, Reade A / Larsen, Christopher / Erben, Young / Majumdar, Ramanath / Jenkins, Sarah M / Kipp, Benjamin R / Lin, Peter T / Maleszewski, Joseph J

    Circulation

    2020  Volume 143, Issue 3, Page(s) 230–243

    Abstract: ... clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide ... of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing ... and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 ...

    Abstract Background: 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.
    Methods: 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.
    Results: Male sex was more common in the COVID-19 group (
    Conclusions: 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.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme 2/biosynthesis ; COVID-19/metabolism ; COVID-19/mortality ; COVID-19/pathology ; Child ; Child, Preschool ; Coronary Thrombosis/metabolism ; Coronary Thrombosis/mortality ; Coronary Thrombosis/pathology ; Female ; Fibrin/metabolism ; Gene Expression Regulation, Enzymologic ; Humans ; Immunohistochemistry ; Infant ; Male ; Middle Aged ; Myocardium/metabolism ; Myocardium/pathology ; SARS-CoV-2/metabolism
    Chemical Substances Fibrin (9001-31-4) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-11-16
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.120.050754
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  6. Article ; Online: Clinico-histopathologic and single-nuclei RNA-sequencing insights into cardiac injury and microthrombi in critical COVID-19.

    Brener, Michael I / Hulke, Michelle L / Fukuma, Nobuaki / Golob, Stephanie / Zilinyi, Robert S / Zhou, Zhipeng / Tzimas, Christos / Russo, Ilaria / McGroder, Claire / Pfeiffer, Ryan D / Chong, Alexander / Zhang, Geping / Burkhoff, Daniel / Leon, Martin B / Maurer, Mathew S / Moses, Jeffrey W / Uhlemann, Anne-Catrin / Hibshoosh, Hanina / Uriel, Nir /
    Szabolcs, Matthias J / Redfors, Björn / Marboe, Charles C / Baldwin, Matthew R / Tucker, Nathan R / Tsai, Emily J

    JCI insight

    2022  Volume 7, Issue 2

    Abstract: Acute cardiac injury is prevalent in critical COVID-19 and associated with increased mortality ... uncommon. To elucidate the pathophysiology of COVID-19-associated cardiac injury, we conducted ... of microthrombi-positive COVID-19 hearts. Our findings warrant further mechanistic study as cardiac fibroblasts ...

    Abstract Acute cardiac injury is prevalent in critical COVID-19 and associated with increased mortality. Its etiology remains debated, as initially presumed causes - myocarditis and cardiac necrosis - have proved uncommon. To elucidate the pathophysiology of COVID-19-associated cardiac injury, we conducted a prospective study of the first 69 consecutive COVID-19 decedents at CUIMC in New York City. Of 6 acute cardiac histopathologic features, presence of microthrombi was the most commonly detected among our cohort. We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak erythrocyte sedimentation rate and C-reactive protein were independently associated with increased odds of microthrombi, supporting an immunothrombotic etiology. Using single-nuclei RNA-sequencing analysis on 3 patients with and 4 patients without cardiac microthrombi, we discovered an enrichment of prothrombotic/antifibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling among cardiac fibroblasts in microthrombi-positive, relative to microthrombi-negative, COVID-19 hearts. Non-COVID-19, nonfailing hearts were used as reference controls. Our study identifies a specific transcriptomic signature in cardiac fibroblasts as a salient feature of microthrombi-positive COVID-19 hearts. Our findings warrant further mechanistic study as cardiac fibroblasts may represent a potential therapeutic target for COVID-19-associated cardiac microthrombi.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; COVID-19/genetics ; COVID-19/metabolism ; COVID-19/pathology ; Female ; Heart Injuries/genetics ; Heart Injuries/metabolism ; Heart Injuries/pathology ; Humans ; Male ; Middle Aged ; Myocardium/metabolism ; Myocardium/pathology ; Prospective Studies ; RNA-Seq ; SARS-CoV-2/metabolism ; Thrombosis/genetics ; Thrombosis/metabolism ; Thrombosis/pathology
    Language English
    Publishing date 2022-01-25
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.154633
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  7. Article: COVID-19-associated Non-Occlusive Fibrin Microthrombi in the Heart

    Bois, Melanie C / Boire, Nicholas A / Layman, Andrew J / Aubry, Marie-Christine / Alexander, Mariam P / Roden, Anja C / Hagen, Catherine E / Quinton, Reade A / Larsen, Christopher / Erben, Young / Majumdar, Ramanath / Jenkins, Sarah M / Kipp, Benjamin R / Lin, Peter T / Maleszewski, Joseph J

    Circulation

    Abstract: ... presentation, COVID-19, is an emergent cause of mortality worldwide. Cardiac complications ... of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi ... microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls ...

    Abstract Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, 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 COVID-19 individuals undergoing postmortem evaluation is provided, with four aims: 1) describe the pathologic spectrum of the myocardium; 2) compare to an alternate viral illness; 3) investigate angiotensin converting enzyme 2 (ACE2) expression; and 4) provide the first description of the cardiac findings in patients with cleared infection. Methods: Study cases were identified from institutional files and included COVID-19 (n=15; 12 active, 3 cleared), influenza A/B (n=6), and non-virally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An ACE2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction (ddPCR). Results: Male sex was more common in the COVID-19 group (p=0.05). Non-occlusive 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 (p=0.006). Four active COVID-19 cases showed focal myocarditis, while one case of cleared COVID-19 showed extensive disease. Arteriolar ACE2 endothelial expression was lower in COVID-19 cases versus controls (p=0.004). ACE2 myocardial expression did not differ by disease category, sex, age or number of patient comorbidities (p=0.69, p=1.00, p=0.46, p=0.65, respectively). SARS-CoV-2 immunohistochemistry showed non-specific staining, while ultrastructural examination and ddPCR were negative for viral presence. Four (26.7%) COVID-19 patients had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. Conclusions: 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 active and cleared COVID-19 patients, but is usually limited in extent. Histologic features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #33197204
    Database COVID19

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