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Functional Effects of Cardiomyocyte Injury in COVID-19.
Siddiq, Mustafa M; Chan, Angel T; Miorin, Lisa; Yadaw, Arjun S; Beaumont, Kristin G; Kehrer, Thomas; Cupic, Anastasija; White, Kris M; Tolentino, Rosa E; Hu, Bin; Stern, Alan D; Tavassoly, Iman; Hansen, Jens; Sebra, Robert; Martinez, Pedro; Prabha, Som; Dubois, Nicole; Schaniel, Christoph; Iyengar-Kapuganti, Rupa; Kukar, Nina; Giustino, Gennaro; Sud, Karan; Nirenberg, Sharon; Kovatch, Patricia; Albrecht, Randy A; Goldfarb, Joseph; Croft, Lori; McLaughlin, Maryann A; Argulian, Edgar; Lerakis, Stamatios; Narula, Jagat; García-Sastre, Adolfo; Iyengar, Ravi.
  • Siddiq MM; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Chan AT; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Miorin L; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Yadaw AS; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Beaumont KG; Department of Medicine and Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  • Kehrer T; Department of Microbiology, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Cupic A; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • White KM; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Tolentino RE; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Hu B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Stern AD; Black Family Stem Cell Center, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Tavassoly I; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Hansen J; Department of Microbiology, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Sebra R; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Martinez P; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Prabha S; Department of Microbiology, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Dubois N; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Schaniel C; Department of Microbiology, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Iyengar-Kapuganti R; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Kukar N; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Giustino G; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Sud K; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Nirenberg S; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Kovatch P; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Albrecht RA; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Goldfarb J; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Croft L; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • McLaughlin MA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Argulian E; Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Lerakis S; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Narula J; Black Family Stem Cell Center, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • García-Sastre A; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
  • Iyengar R; Sema4, a Mount Sinai Venture, Stamford, Connecticut, USA.
J Virol ; 96(2): e0106321, 2022 01 26.
Article in English | MEDLINE | ID: covidwho-1476388
ABSTRACT
COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-6 / Interleukin-10 / Myocytes, Cardiac / Interleukin-1beta / Induced Pluripotent Stem Cells / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.01063-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-6 / Interleukin-10 / Myocytes, Cardiac / Interleukin-1beta / Induced Pluripotent Stem Cells / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study Limits: Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.01063-21