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Fukuma, Nobuaki J; Brener, Michael; Hulke, Michelle; Fukuma, Nobuaki; Golob, Stephanie; Zilinyi, Robert; Zhou, Zhipeng; Tzimas, Christos; Russo, Ilaria; McGroder, Claire; Chong, Alexander; Pfeiffer, Ryan; Geping, Zhang; Uhlemann, Anne-Catrin; Moses, Jeffrey; Leon, Martin; Burkhoff, Daniel; Maurer, Mathew; Redfors, Bjorn; Uriel, Nir; Szabolcs, Matthias; Marboe, Charles C; Baldwin, Matthew; Tucker, Nathan R

Abstract 14422: Molecular Pathogenesis of Cardiac Microthrombi in Fatal Covid-19: Insights from Clinico-histopathologic and Single Nuclei RNA Sequencing Analyses

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  • Medientyp: E-Artikel
  • Titel: Abstract 14422: Molecular Pathogenesis of Cardiac Microthrombi in Fatal Covid-19: Insights from Clinico-histopathologic and Single Nuclei RNA Sequencing Analyses
  • Beteiligte: Fukuma, Nobuaki J; Brener, Michael; Hulke, Michelle; Fukuma, Nobuaki; Golob, Stephanie; Zilinyi, Robert; Zhou, Zhipeng; Tzimas, Christos; Russo, Ilaria; McGroder, Claire; Chong, Alexander; Pfeiffer, Ryan; Geping, Zhang; Uhlemann, Anne-Catrin; Moses, Jeffrey; Leon, Martin; Burkhoff, Daniel; Maurer, Mathew; Redfors, Bjorn; Uriel, Nir; Szabolcs, Matthias; Marboe, Charles C; Baldwin, Matthew; Tucker, Nathan R
  • Erschienen: Ovid Technologies (Wolters Kluwer Health), 2021
  • Erschienen in: Circulation, 144 (2021) Suppl_1
  • Sprache: Englisch
  • DOI: 10.1161/circ.144.suppl_1.14422
  • ISSN: 0009-7322; 1524-4539
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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 in-hospital 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, P non-linearity 0.015, P association =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.
  • Zugangsstatus: Freier Zugang