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Molecular pathogenesis of cardiac microthrombi in fatal covid-19: Insights from clinicohistopathologic and single nuclei rna sequencing analyses
Circulation ; 144(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1632416
ABSTRACT
Cardiac microthrombi are postulated to underlie cardiac injury in critical COVID-19. To determine pathogenic mechanism(s) of cardiac injury in fatal COVID-19, we conducted a single-center prospective cohort study of 69 consecutive COVID-19 decedents. Microthrombi was the most commonly detected acute cardiac histopathologic feature (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with inhospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi (ESR, Pnonlinearity 0.015, Passociation=0.008;CRP per 20mg/L increase, OR 1.17, 95%CI 1.00-1.36). Using single nuclei RNA-sequence analysis, we discovered an enrichment of prothrombotic, anti-fibrinolytic, and extracellular matrix signaling amongst cardiac fibroblasts in microthrombi-positive COVID-19 hearts, compared with microthrombi-negative COVID-19 hearts and non-COVID-19 donor hearts. Our cumulative findings identify these specific transcriptomic changes in cardiac fibroblasts as salient features of COVID-19-associated cardiac microthrombi.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Etiology study / Observational study / Prognostic study / Risk factors Language: English Journal: Circulation Year: 2021 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Etiology study / Observational study / Prognostic study / Risk factors Language: English Journal: Circulation Year: 2021 Document Type: Article