SARS-CoV-2 and Cytomegalovirus Coinfection in a Patient With Myocarditis and Severe COVID-19 Infection.

A 29-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, complicated by septic shock, was admitted to the intensive care unit (blood pressure: 70/50 mm Hg; heart rate: 120 per minute; oxygen saturation: 90%). Laboratory tests revealed elevated parameters of inflammation and myocardial damage: C-reactive protein (CRP): 444, 6 mg/L; procalcitonin: 18 ng/mL; ferritin: 3504 ng/mL; elevation of troponin (TnI): 2375.1 pg/mL; N-terminal pro b-type natriuretic peptide (Nt-proBNP): 12,788 pg/mL. Electrocardiogram (ECG) showed normal sinus rhythm and no signs of ischemia. The patient developed acute respiratory distress syndrome and heart failure, requiring invasive mechanical ventilation. Transthoracic echocardiography revealed decreased left ventricular ejection fraction (LVEF) 28%, global longitudinal strain (GLS) –7.8%, and no pericardial effusion. Cardiac magnetic resonance imaging showed the presence of hypokinesis of all walls, myocardial edema (subendocardium), pericardial effusion (6 mm), and the presence of late gadolinium enhancement. Myocarditis was diagnosed according to the Lake Louise Criteria. Endomyocardial biopsy was performed 11 days after the onset of the symptoms and revealed diffused lymphomonocytic inflammatory infiltrates: LCA+ > 14 cells/mm2, CD3+ > 7 cells/mm2, monocytic infiltrates CD68+ > 4 cells/mm2, and myocytolysis without features of significant fibrosis. Staining against immunoglobulin G (IgG)4 was negative. The microscopic picture indicated chronic active inflammatory myocarditis (Figs. 1 and 2). Virologic investigation revealed the presence of SARS-CoV-2 RNA in biopsy (Ct = 38) and peripheral blood (Ct = 34), with concomitant presence of CMV (Cytomegalovirus) DNA in peripheral blood (230 copies/mL) and in blood from cardiac cavities (100 copies/mL). Therapy with ganciclovir and methylprednisolone (25 mg per day) was introduced, with further modification to prednisone (35 mg per day) and colchicine (0.5 mg per day).Figure 2Electron microscopy revealed leukocytic infiltrate and platelet containing round structures smaller than 130 nm (which may correspond to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] virions) in sarcoplasmic reticulum (bold red arrows), numerous swollen pleiotropic mitochondria with blurred mitochondrial cristae (red arrows).View Large Image Figure ViewerDownload Hi-res image Download (PPT) During a follow-up visit 4 months after hospitalization, LVEF was 55%, and GLS was –16,6%, New York Heart Association class I, blood pressure: 136/74 mm Hg, heart rate: 87 per minute. Five months after hospitalization, cytomegalovirus (CMV) serologic tests were performed, and the results were as follows: IgG positive (236,4 AU/mL), IgM negative (0,63 index). To the best of our knowledge, this is the first case of a patient with severe myocarditis caused by SARS-COV 2 infection, confirmed by real-time polymerase chain reaction (RT-PCR) of a myocardial biopsy and CMV coinfection confirmed by the presence of CVM DNA in the blood. Earlier work indicated the possibility of a more severe course of SARS-COV 2 infection in CMV-postinfected patients, based on the presence of IgG antibodies to CMV (more frequent hospitalizations and hospital deaths in the coinfection group) or CMV reactivation in immunocompetent critically ill patients.1Gatto I. Biagioni E. Coloretti I. et al.on behalf of the Modena COVID-19 Working Group. Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality.Intensive Care Med. 2022; 48: 706-713Crossref PubMed Scopus (25) Google Scholar Moreover, analysis of the biopsy by electron microscopy revealed an enlarged sarcoplasmic reticulum with the presence of oval structures corresponding in size to SARS-COV-2 virus. This image may explain the mechanism of increased prothrombotic readiness observed in patients with COVID-19.2Barrett T.J. Bilaloglu S. Cornwell M. et al.Platelets contribute to disease severity in COVID-19.J Thromb Haemost. 2021; 19: 3139-3153Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar CMV in patients with COVID-19 could be a risk factors of the severity course of disease, hospitalization, and mortality. No funding was provided for this paper.