Functional Effects of Cardiomyocyte Injury in COVID-19.

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.

Obstructive sleep apnoea and left ventricular diastolic dysfunction among first responders to the 9/11 World Trade Center terrorist attack: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnoea (OSA) is often linked to cardiovascular disease. A limited number of studies have reported an association between OSA and left ventricular diastolic dysfunction (LVDD). However, prior studies were performed on small patient populations. Studies have shown a high prevalence of OSA among first responders to the 9/11 World Trade Center (WTC) terrorist attack. We investigated the relationship between OSA and LVDD in a large population of WTC responders. DESIGN: Cross-sectional study. SETTING: One-time screening programme as part of the WTC-CHEST Study (NCT10466218), performed at a quaternary medical centre in New York City, from November 2011 to June 2014. PARTICIPANTS: A total of 1007 participants with mean age of 51 years of mostly non-Hispanic white men were evaluated. Patients from the WTC Health Program-Clinical Center of Excellence, who were over the age of 39 years, were eligible to participate. RESULTS: Evaluation of those without OSA diagnosis showed no significant association with LVDD when comparing those screened (Berlin Questionnaire) as OSA high risk versus OSA low risk (p=0.101). Among those diagnosed with LVDD, there was a significant association when comparing those with and without patient-reported OSA (OR 1.50, 95% CI 1.13 to 2.00, p=0.005), but the significance was not maintained after adjusting for pertinent variables (OR 1.3, 0.94 to 1.75, p=0.119). Notably, comparing those with OSA diagnosis and those low risk of OSA, the OR for LVDD was significant (1.69, 1.24 to 2.31, p=0.001), and after adjusting for waist-hip ratio, diabetes and coronary artery calcium score percentile, the relationship remained significant (OR 1.45, 1.03 to 2.04, p=0.032). CONCLUSION: The strong association of OSA with LVDD in this population may inform future guidelines to recommend screening for LVDD in high-risk asymptomatic patients with OSA.

Physiology of cardiomyocyte injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System shows 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 integrate cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with SARS-CoV-2 in the presence of interleukins, with clinical findings, to investigate 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 interleukins. We find that interleukin treatment and infection results in disorganization of myofibrils, extracellular release of troponin-I, and reduced and erratic beating. Although interleukins do not increase the extent, they increase the severity of 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 prior 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 can underlie the heart disease in COVID-19 patients.