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Smoking Gun Found for Virus in MIS-C Heart Damage Case

— First case report documenting viral particles in the heart in MIS-C

MedpageToday
A computer rendering of coronaviruses in the heart

SARS-CoV-2 turned up extensively in the heart of a girl who died of cardiac complications from multisystem inflammatory syndrome in children (MIS-C), according to a case report from Brazil.

Viral particles were found in the 11-year-old's cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells, Marisa Dolhnikoff, MD, of the Universidade de São Paulo, Brazil, and colleagues .

"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 wrote.

Cardiogenic shock and signs of myocarditis have been not uncommonly reported with MIS-C since a wave of cases was identified trailing about a month behind COVID-19 surges in Europe and New York in the spring.

The mechanism of heart failure, though, in these patients and how it relates to the SARS-CoV-2 virus has been unclear, the researchers noted. Possibilities are that the virus triggers a severe systemic immune response similar to that suspected in Kawasaki disease, or it may cause direct tissue damage, or both.

In adults, viral presence in the heart has been well documented by COVID-19 autopsy studies, even when myocarditis had not been suspected clinically, but without an influx of inflammatory cells. Cardiac MRI on adults suggested lingering cardiac inflammation after COVID-19 recovery, although .

These new "pathological observations support the hypothesis that the direct effect of SARS-CoV-2 infection on cardiac tissue was a major contributor to myocarditis and heart failure in our patient," they wrote.

However, a more cautious take came from Kevin Friedman, MD, of Boston Children's Hospital and a member of the American Heart Association's Young Hearts Council and its Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee.

"The patient was still PCR-positive and had active viral infection in multiple organs, so I think it is more representative of severe, acute COVID 19 disease, which has been reported to involve the heart and cause acute, severe left ventricular dysfunction in lots of adult cases," he told ľֱ.

"I am not sure that this case and the biopsy results are representative of the broader group of children who develop cardiac dysfunction later on due to MIS-C, as the PCR is typically negative at that time," he added. "While there is inflammation of multiple organs in MIS-C, it is unlikely that there is active virus in the organs in MIS-C."

The girl, who had been otherwise healthy and had no detectable immune disorder, developed cardiac failure and died 1 day after hospital admission.

Her initial symptoms were fever for 7 days, painful swallowing, myalgia, and abdominal pain. Two other symptoms typical of Kawasaki disease were present as well: non-exudative conjunctivitis and cracked lips. At pediatric ICU admission, she had respiratory distress and hypoxia, along with signs of congestive heart failure.

SARS-CoV-2 was detected in cardiac tissue by RT-PCR and electron microscopy. Autopsy showed intense and diffuse tissue inflammation in the heart tissue along with necrosis of cardiomyocytes. A small number of eosinophils were found.

"Despite the evident systemic inflammation and final progression to multiorgan failure, clinical, echocardiographic, and laboratory findings strongly indicated that heart failure was the main determinant of the fatal outcome," Dolhnikoff's group wrote.

They proposed, based on their combination of findings, that "infection of cardiomyocytes probably leads to local inflammation in response to cell injury; both the virus-induced injury and the inflammatory response could lead to necrosis of cardiomyocytes. The finding of viral particles in neutrophils supports the idea of virus-induced inflammation."

"Hopefully, our findings could help to shed light on the understanding of the complex interaction between SARS-CoV-2 infection, MIS-C, and cardiac dysfunction in children and adolescents with COVID-19," the group concluded.

Disclosures

The researchers disclosed no relevant relationships with industry.

Primary Source

The Lancet Child and Adolescent Health

Dolhnikoff M, et al "SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome" Lancet Child Adolesc Health 2020; DOI: 10.1016/ S2352-4642(20)30257-1.