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SARS-CoV-2 has been found in cardiac tissue of a child from Brazil with multisystem inflammatory syndrome (MIS-C) related to COVID-19 who presented with myocarditis and died of heart failure.
It's believed to be the first evidence of direct infection of heart muscle cells by the virus; viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.
The case is described in a report published online August 20 in The Lancet Child & Adolescent Health.
"The presence of the virus in various cell types of cardiac tissue, as evidenced by electron microscopy, shows that myocarditis in this case is likely a direct inflammatory response to the virus infection in the heart," first author Marisa Dolhnikoff, MD, Department of Pathology, University of Sao Paulo, Brazil, told Medscape Medical News.
There have been previous reports in adults with COVID-19 of both SARS-CoV-2 RNA by reverse transcription polymerase chain reaction (RT-PCR) and viral particles by electron microscopy in cardiac tissue from endomyocardial specimens, the researchers note. One of these reports, published in April by Tavazzi and colleagues, they write, "detected viral particles in cardiac macrophages in an adult patient with acute cardiac injury associated with COVID-19; no viral particles were seen in cardiomyocytes or endothelial cells.
"Our case report is the first to our knowledge to document the presence of viral particles in the cardiac tissue of a child affected by MIS-C," they add. "Moreover, viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells."
"Concerning" Case Report
"This is a concerning report as it shows for the first time that the virus can actually invade the heart muscle cells themselves," C. Michael Gibson, MD, CEO of the Baim Institute for Clinical Research in Boston, Massachusetts, told Medscape Medical News.
"Previous reports of COVID-19 and the heart found that the virus was in the area outside the heart muscle cells. We do not know yet the relative contribution of the inflammatory cells invading the heart, the release of blood-borne inflammatory mediators, and the virus inside the heart muscle cells themselves to heart damage," Gibson said.
The patient was a previously healthy 11-year-old girl of African descent with MIS-C related to COVID-19. She developed cardiac failure and died after one day in the hospital, despite aggressive treatment.
SARS-CoV-2 RNA was detected on a postmortem nasopharyngeal swab and in cardiac and pulmonary tissues by RT-PCR.
Postmortem ultrasound examination of the heart showed a "hyperechogenic and diffusely thickened endocardium (mean thickness 10 mm), a thickened myocardium (18 mm thick in the left ventricle), and a small pericardial effusion," Dolhnikoff and colleagues report.
Histopathological exam revealed myocarditis, pericarditis, and endocarditis characterized by infiltration of inflammatory cells. Inflammation was mainly interstitial and perivascular, associated with foci of cardiomyocyte necrosis and was mainly composed of CD68+ macrophages, a few CD45+ lymphocytes, and a few neutrophils and eosinophils.
Electron microscopy of cardiac tissue revealed spherical viral particles in shape and size consistent with the Coronaviridae family in the extracellular compartment and within cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts.
Microthrombi in the pulmonary arterioles and renal glomerular capillaries were also seen at autopsy. SARS-CoV-2-associated pneumonia was mild.
Lymphoid depletion and signs of hemophagocytosis were observed in the spleen and lymph nodes. Acute tubular necrosis in the kidneys and hepatic centrilobular necrosis, secondary to shock, were also seen. Brain tissue showed microglial reactivity.
"Fortunately, MIS-C is a rare event and, although it can be severe and life threatening, most children recover," Dolhnikoff commented.
"This case report comes at a time when the scientific community around the world calls attention to MIS-C and the need for it to be quickly recognized and treated by the pediatric community. Evidence of a direct relation between the virus and myocarditis confirms that MIS-C is one of the possible forms of presentation of COVID-19 and that the heart may be the target organ. It also alerts clinicians to possible cardiac sequelae in these children," she added.
Experts Weigh In
Scott Aydin, MD, medical director, Pediatric Cardiac Intensive Care, Mount Sinai Kravis Children's Hospital in New York City, told Medscape Medical News this case report is "unfortunately not all that surprising."
"Since the initial presentations of MIS-C several months ago, we have suspected mechanisms of direct and indirect injury to the myocardium. This important work is just the next step in further understanding the mechanisms of how COVID-19 creates havoc in the human body and the choices of possible therapies we have to treat children with COVID-19 and MIS-C," said Aydin, who was not involved with the case report.
Anish Koka, MD, a cardiologist in private practice in Philadelphia, Pennsylvania, noted that, in these cases, endomyocardial biopsy is "rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis."
"While reports like this are sure to spawn viral tweets, it's vital to understand that it's not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in," Koka told Medscape Medical News.
He noted that in the case of the young girl who died, it took high PCR-cycle threshold values to isolate virus from the lung and heart samples.
"This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs," said Koka, who was also not associated with the case report.
This research had no specific funding. The authors have declared no competing interests. Aydin has disclosed no relevant financial relationships. Koka has disclosed financial relationships with Boehringer Ingelheim and Jardiance.
Lancet Child Adolesc Health. Published online August 20, 2020. Case report
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Cite this: First Evidence of SARS-CoV-2 in Heart Cells - Medscape - Aug 24, 2020.