Cellular Therapy Shows Promise for COVID-Related MIS-C in Kids

NEW YORK (Reuters Health) – Two children severely ill with COVID-19-related multisystem inflammatory syndrome (MIS-C) showed significant improvement within 24 hours of receiving remestemcel-L, an investigational cellular therapy being developed by Mesoblast Inc.

“This treatment appears promising as a novel immunomodulatory cellular therapy for children with clinically significant cardiovascular manifestations of MIS-C,” Dr. Allison Eckard of The Medical University of South Carolina (MUSC) in Charleston and colleagues report in Pediatrics.

MIS-C is an uncommon but potentially life-threatening post-infectious autoimmune process associated with COVID-19 that may include cardiovascular dysfunction, hemodynamic instability, shock and multisystem organ failure. With no standard or approved treatments, current care consists of nonspecific anti-inflammatory and antithrombotic therapies.

Remestemcel-L is an investigational mesenchymal stromal cell therapy with “beneficial anti-inflammatory, immunomodulatory, endothelial function, and vascular stabilizing effects, which align well with the pathophysiology of MIS-C,” the researchers say.

The children described in the Pediatrics paper are the first two patients with life-threatening MIS-C to receive remestemcel-L under an expanded-access program – one was a 4-year-old non-Hispanic Black boy and the other a 10-year old non-Hispanic Black girl.

Both were treated at MUSC during August to September and both had “strikingly similar” presentations, the authors report. Both were previously healthy and experienced a preceding illness lasting about five days and consisting of high fever (39.0 to 40.6°C), gastrointestinal symptoms, and generalized malaise.

On presentation, both children had severe clinical illness, including hemodynamic instability, hypotension, acute kidney injury and shock requiring vasopressors. They also had significant myocardial dysfunction, with markedly elevated biomarkers of cardiac injury and/or congestion and systemic inflammation and/or coagulation. One child also had changes in mental status and significant respiratory distress (secondary to poor cardiac function and fluid overload), which led to intubation.

In neither case was there a known exposure to someone with COVID-19 or symptoms suggestive of COVID-19 in the preceding month. However, both children had positive immunoglobulin G antibodies against SARS-CoV-2 nucleocapsid and spike proteins with a negative SARS-CoV-2 PCR test.

While both children improved somewhat with standard treatment for MIS-C, left ventricular ejection fraction remained reduced and inflammatory biomarkers remained significantly elevated.

“When treated with two intravenous doses of remestemcel-L separated by 48 hours, rapid normalization of left ventricular ejection fraction, notable reductions in biomarkers of systemic and cardiac inflammation, and improved clinical status occurred,” Dr. Eckard and colleagues report.

Although both children were showing some level of clinical improvement when they received remestemcel-L, the data suggest that this therapy “contributed to further improvements in myocardial and endothelial function and promoted additional reductions in systemic and cardiac inflammation,” they note.

Neither child experienced any adverse effects associated with remestemcel-L therapy.

“This therapy holds promise as a novel treatment for MIS-C,” the researchers conclude.

Mesoblast, Inc provided remestemcel-L at no cost to the patients. One author on the paper is a consultant to Mesoblast and one is an employee of the company.

SOURCE: https://bit.ly/32D2XgH Pediatrics, online April 23, 2021.

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