Infective and nonbacterial thrombotic endocarditis in patients with post-COVID-19 viral-immune myocarditis

The possibility of heart inflammation (both myocardial and endocardial) months after a coronavirus disease 2019 (COVID-19) has not been practically studied, especially since approaches to the treatment of myocarditis in combination with various endocarditis forms have not been developed.

Aim. To study the prevalence and mechanisms of SARS-CoV-2-associated endocardial injury in patients with morphologically verified post-COVID-19 myocarditis, as well as to develop approaches to comprehensive therapy.

Material and methods. The study included 18 patients with severe morphologically verified post-COVID-19 myocarditis (men, 9; 51,1±9,4 years; 35 to 66 years). Patients with prior verified myocarditis/myocardial infarction, rheumatic heart disease, and systemic immune diseases were excluded. The average time after COVID-19 was 6,5 [3.5; 10] months The diagnosis of myocarditis was confirmed by endomyocardial biopsy (including immunohistochemical examination with antibodies to CD3, CD20, CD45, CD68, and to SARS-CoV-2 antigens; polymerase chain reaction for SARS-CoV-2 RNA, DNA of cardiotropic viruses). The blood level of anticardiac antibodies was determined by indirect immunofluorescence. In addition, echocardiography, magnetic resonance imaging (n=8), cardiac multislice tomography (n=1), and coronary angiography (n=14) were performed.

Results. Biopsy revealed active (n=12) and borderline (n=3) lymphocytic myocarditis, eosinophilic (n=2) and giant cell (n=1) myocarditis. In 4 patients, nonbacterial thrombotic endocarditis (NBTE) with parietal and intravascular thrombosis was diagnosed, and in one patient — infective endocarditis (IE) of the bicuspid aortic valve. Myocardial persistence of SARS-CoV-2 was detected in 72% of cases (in 3 patients — with NBTE; in 1 — with IE; in 9 — without endocarditis). Titers of anticardiac antibodies increased by 3-4 times in 94% of patients. Patients with endocarditis were characterized by larger heart chambers, lower ejection fraction (27,5±6,6 vs 36,0±13,4%), more severe pulmonary hypertension, and valvular regurgitation. Intraventricular thrombosis according to echocardiography/magnetic resonance imaging and cardiac embolism was not observed. Treatment in all patients included methylprednisolone at an average dose of 24 mg a day. In 10 patients, the result was monitored for at least 3 months as follows: the ejection fraction was 46,0±12,7% and 44,3±7,3% in patients with and without endocarditis, respectively.

Conclusion. Endocarditis in patients with post-COVID-19 myocarditis was detected in 28% (1 patient — IE; 4 — NBTE). The key mechanisms of post-COVID-19 myocarditis and NBTE are long-term (up to 18 months) myocardial persistence of SARS-Cov-2 and the development of an autoimmune reaction. Endocarditis was diagnosed in more severe patients, including those with giant cell and eosinophilic myocarditis. The effectiveness of steroid therapy in combination with anticoagulants in patients with NBTE requires further study. In case of IE, steroids can also be used in the treatment of myocarditis (in combination with antibiotics and immunoglobulin).

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