- This study examined data from 41 sequential autopsies of patients who died of COVID-19 between March and July 2020
- 30 patients (73%) had myocardial cells infected by SARS-CoV-2 and four had myocarditis
- Among the 38 patients who died in the hospital, all four patients with myocarditis required renal replacement therapy compared with 6/34 without myocarditis (P=0.002)
- New atrial fibrillation or premature atrial complexes occurred only in patients with cardiac SARS-CoV-2 infection (11/24 vs. 0/10 without infection; P=0.01)
- Nonbiologic immunosuppression (predominantly with corticosteroids) was associated with significantly lower incidences of myocarditis and cardiac infection by SARS-CoV-2, which may help explain the efficacy of corticosteroids against COVID-19
Arrhythmias and acute heart failure have been reported in patients with COVID-19, and autopsy studies have documented multiple types of cardiac pathology, from microvascular thrombi to full myocarditis.
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To investigate the effects of cardiac pathology, Mayara Bearse, MD, research fellow, and James Stone, MD, PhD, director of Autopsy and Cardiovascular Pathology, both of the Department of Pathology at Massachusetts General Hospital, and colleagues examined data from 41 sequential autopsies of patients who died of COVID-19 between March and July 2020, using in situ hybridization and NanoString transcriptome profiling.
They report in Modern Pathology that infection of the heart by SARS-CoV-2 is common, although limited, and is linked to differences in clinical features and COVID-19 treatment.
Pathologically Defined Groups
The researchers stratified patients into three groups:
- Four who had SARS-CoV-2–infected cells in the myocardium (V+) and had myocarditis (M+)
- 26 who were V+ and M−
- 11 who were V− and M−
Thus, 30 patients (73%) had infected myocardial cells and four had myocarditis. In three patients the myocarditis was limited to multiple small discrete foci; in the fourth, it was more extensive.
The three groups did not differ with regard to individual comorbidities or a composite risk factor score that considered age, body mass index, heart weight, severe coronary artery disease, and previous history of diabetes, hypertension, hyperlipidemia, myocardial infarction, autoimmune disease or smoking.
Variation in Cardiac Inflammation
Compared with the 11 patients who did not have a cardiac infection by SARS-CoV-2, the 30 V+ patients had increased densities of myocardial CD68+ macrophages, CD3+ T cells and CD4+ helper T cells. The four patients with myocarditis had increased densities of the same cell types when compared with the V+M− and V−M− groups.
Key Clinical Findings
Renal replacement therapy (RRT)—Of the 38 patients who died in the hospital, 4/4 with myocarditis required RRT compared with 6/34 without myocarditis (P=0.002).
Cardiac rhythm assessment was available for 34 patients who died in the hospital and did not have a prior history of atrial fibrillation. In this group, atrial fibrillation or premature atrial complexes occurred only in patients with cardiac SARS-CoV-2 infection (11/24 vs. 0/10 without infection; P=0.01).
Echocardiography was performed on the four myocarditis patients (within one week of death in three cases). All four had normal left ventricular function and myocarditis was not the cause of death in any of them.
Serious cardiac outcomes—Two patients had cardiac-related causes of death (acute heart failure or refractory ventricular tachycardia) and three had reduced left ventricular ejection fraction; all had SARS-CoV-2–infected myocardial cells.
Correlations Between Clinical Features and Myocardial Inflammation
Regardless of the presence of myocarditis or cardiac SARS-CoV-2 infection, myocardial inflammation correlated positively and strongly with the duration of symptoms and hospitalization and negatively with the red blood cell count. Myocardial inflammation may result in many patients having a long COVID-19 illness prior to death.
SARS-CoV-2 infection of myocardial cells was less prevalent in patients who received nonbiologic immunosuppressants (predominantly corticosteroids) than in those who did not (7/14 vs. 21/24; P=0.02). Similarly, patients treated with nonbiologic immunosuppressants had a lower prevalence of myocarditis than those treated with interleukin-6 blockade without nonbiologic immunosuppression (0/14 vs. 2/3; P=0.02).
Part of the efficacy of corticosteroids against COVID-19 might be related to reduced cardiac infection by the virus along with reduced myocardial inflammation and myocarditis.
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