ABSTRACT
Background: Myocardial involvement in COVID-19 has been described as either coronary artery related ischemic lesions, lymphocyte myocarditis or microangiopathy. Assessment of the link between COVID-19 and the cause of death has been hampered by the limited number of autopsies performed during the pandemics and risk factors associated with the type and extent of myocardial damage remain poorly described. In Russia, the mandatory autopsy approach has been advocated for the cases of suspected COVID- 19 related deaths. Purpose: To describe the prevalence, extent and risk factors associated with myocardial damage in an unselected cohort of patients deceased with COVID-19. Methods: Consecutive patients with PCR-confirmed or suspected COVID- 19 who died either in-hospital (clinical autopsy) or out-of-hospital (forensic autopsy) during COVID-19 pandemic underwent post-mortem PCR on pulmonary parenchymal tissue. Tissue PCR-positive cases were referred for histology study of pulmonary and extrapulmonary organ specimens through a central laboratory. Based on the extent of diffuse alveolar damage (DAD), COVID-19 was categorized as either being related to death or a concomitant condition not associated with death. Myocardial involvement was categorized as either (1) coronary artery related myocardial infarction, (2) microangiopathy with interstitial edema and erythrocyte aggregates occluding the capillaries with or without lymphomononuclear infiltration and (3) lymphocyte myocarditis. The presence of myocardial involvement was assessed with regard to age, gender and autopsy-verified significant coronary artery disease (CAD) and diabetes (information available only for the clinical autopsy cohort). Results: 102 autopsies were included, of whom 42 were clinical and 60 forensic (age 73±15 years, 50% men;58% had CAD). Ten patients from the clinical autopsy cohort had diabetes (24%). Deaths were COVID-19 related in 80 patients (78%). Myocardial infarction was noted in 3 (2.9%) patients. Microangiopathy was seen in 45 (44%) and lymphocyte myocarditis in 2 (1.9%) patients, of whom it was the primary cause of death in one. The prevalence of microangiopathy did not differ between patients with and without significant DAD (46% vs 45%, p=0.848). Patients with diabetes were more likely to have microangiopathy with lymphomononuclear infiltration in the myocardium than patients without diabetes (40% vs 3.1%, p=0.008;OR=22, 95% CI 1.63-305, p=0.020 after adjustment for age, gender and CAD) Conclusion: Systematically performed autopsies revealed causative association between SARS-CoV2 and death in the vast majority. Myocardial involvement was observed in nearly half of the patients and was not related to the extent of DAD. Myocarditis appears to be a rare finding, though it can be the primary cause of death. Microangiopathy with capillary occlusion and lymphomononuclear infiltration in the myocardium was associated with the history of diabetes.
ABSTRACT
IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.