Atrial inflammation and microvascular thrombogenicity are increased in deceased COVID-19 patients.

BACKGROUND: Histopathological studies have shown inflammation, cardiomyocyte injury, and microvascular thrombosis in the ventricular myocardium of patients with coronavirus disease 2019 (COVID-19). However, although atrial dysfunction is common in COVID-19, little is known about histopathological changes in the atria of the heart. We therefore analyzed inflammation, cardiomyocyte injury, and microvascular thrombogenicity in the atria of deceased patients with COVID-19. METHODS: Atrial tissue was obtained from autopsied COVID-19 (n=16) patients and control patients (n=10) and analyzed using immunohistochemistry. The infiltration of CD45+ leukocytes, CD3+ T lymphocytes, CD68+ macrophages, MPO+ neutrophils, and Tryptase+ mast cells were quantified as well as cardiomyocyte damage and microvascular thrombosis. In addition, Tissue Factor (TF) and Factor XII (FXII) were quantified as markers of microvascular thrombogenicity. RESULTS: The numbers of lymphocytes, macrophages, and neutrophils were significantly increased in the atrial myocardium and epicardial atrial adipose tissue of COVID-19 patients compared with the control group. This was accompanied by dispersed cardiomyocyte injury, the occasional presence of microvascular thrombosis, and an increased presence of TF and FXII in the microvascular endothelium. CONCLUSIONS: Severe COVID-19 induces inflammation, cardiomyocyte injury, and microvascular thrombosis in the atria of the heart.

NOX2 and NOX5 are increased in cardiac microvascular endothelium of deceased COVID-19 patients.

BACKGROUND: Cardiac injury and inflammation are common findings in COVID-19 patients. Autopsy studies have revealed cardiac microvascular endothelial damage and thrombosis in COVID-19 patients, indicative of microvascular dysfunction in which reactive oxygen species (ROS) may play a role. We explored whether the ROS producing proteins NOX2, NOX4 and NOX5 are involved in COVID-19-induced cardio-microvascular endothelial dysfunction. METHODS: Heart tissue were taken from the left (LV) and right (RV) ventricle of COVID-19 patients (n = 15) and the LV of controls (n = 14) at autopsy. The NOX2-, NOX4-, NOX5- and Nitrotyrosine (NT)-positive intramyocardial blood vessels fractions were quantitatively analyzed using immunohistochemistry. RESULTS: The LV NOX2+, NOX5+ and NT+ blood vessels fractions in COVID-19 patients were significantly higher than in controls. The fraction of NOX4+ blood vessels in COVID-19 patients was comparable with controls. In COVID-19 patients, the fractions of NOX2+, NOX5+ and NT+ vessels did not differ significantly between the LV and RV, and correlated positively between LV and RV in case of NOX5 (r = 0.710; p = 0.006). A negative correlation between NOX5 and NOX2 (r = -0.591; p = 0.029) and between NOX5 and disease time (r = -0.576; p = 0.034) was noted in the LV of COVID-19 patients. CONCLUSION: We show the induction of NOX2 and NOX5 in the cardiac microvascular endothelium in COVID-19 patients, which may contribute to the previously observed cardio-microvascular dysfunction in COVID-19 patients. The exact roles of these NOXes in pathogenesis of COVID-19 however remain to be elucidated.

Cardiac inflammation and microvascular procoagulant changes are decreased in second wave compared to first wave deceased COVID-19 patients.

BACKGROUND: Compelling evidence has shown cardiac involvement in COVID-19 patients. However, the overall majority of these studies use data obtained during the first wave of the pandemic, while recently differences have been reported in disease course and mortality between first- and second wave COVID-19 patients. The aim of this study was to analyze and compare cardiac pathology between first- and second wave COVID-19 patients. METHODS: Autopsied hearts from first- (n = 15) and second wave (n = 10) COVID-19 patients and from 18 non-COVID-19 control patients were (immuno)histochemically analyzed. CD45+ leukocyte, CD68+ macrophage and CD3+ T lymphocyte infiltration, cardiomyocyte necrosis and microvascular thrombosis were quantified. In addition, the procoagulant factors Tissue Factor (TF), Factor VII (FVII), Factor XII (FXII), the anticoagulant protein Dipeptidyl Peptidase 4 (DPP4) and the advanced glycation end-product N(ε)-Carboxymethyllysine (CML), as markers of microvascular thrombogenicity and dysfunction, were quantified. RESULTS: Cardiac inflammation was significantly decreased in second wave compared to first wave COVID-19 patients, predominantly related to a decrease in infiltrated lymphocytes and the occurrence of lymphocytic myocarditis. This was accompanied by significant decreases in cardiomyocyte injury and microvascular thrombosis. Moreover, microvascular deposits of FVII and CML were significantly lower in second wave compared to first wave COVID-19 patients. CONCLUSIONS: These results show that in our cohort of fatal COVID-19 cases cardiac inflammation, cardiomyocyte injury and microvascular thrombogenicity were markedly decreased in second wave compared to first wave patients. This may reflect advances in COVID-19 treatment related to an increased use of steroids in the second COVID-19 wave.