First There Was MIS-C, Now There Is MIS-A
By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: Multisystem inflammatory syndrome in adults (MIS-A), similar to multisystem inflammatory syndrome in children (MIS-C), is described by the Centers for Disease Control and Prevention.
SOURCE: Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection — United Kingdom and United States, March–August 2020. MMWR Morb Mortal Wkly Rep 2020;69:1450-1456.
The occurrence of the multisystem inflammatory syndrome in children (MIS-C) has been linked to SARS-CoV-2 infection. The case definition of this illness, which may resemble Kawasaki disease, includes the presence of fever, laboratory evidence of an inflammatory response, and illness severe enough to require hospitalization with involvement of at least two organ systems in an individual younger than 21 years of age — all without a reasonable alternative diagnosis. Also required is a positive current or recent SARS-CoV-2 real time polymerase chain reaction (RT-PCR), antigen, or serology — or exposure within the previous four weeks to an individual with suspected or confirmed COVID-19.
Beginning in June 2020, case reports of a similar illness began to be reported in adults, but with at least one major difference — the lack of severe respiratory illness. This syndrome has been called the multisystem inflammatory syndrome in adults (MIS-A).
Centers for Disease Control and Prevention (CDC) investigators identified cases of MIS-A from voluntary reports and published case reports, with the former yielding nine cases and the latter yielding seven cases. These 16 patients ranged in age from 21 to 50 years; nine were women; nine were African-American, and one was of African origin but was from the United Kingdom. Nine had no reported comorbidity.
Twelve patients had measured or subjective fever on hospital admission. All 16 patients had cardiac abnormalities, including arrhythmias, elevated troponin, and/or echocardiographic evidence of ventricular dysfunction. Gastrointestinal symptoms were present in 13 patients, and five patients had dermatologic manifestations and/or mucositis. Respiratory symptoms were, by definition, at most minimal, but chest imaging identified ground glass opacities in 10 patients, while four patients had pleural effusions. Lymphocytopenia was present in 10 patients. One or more inflammatory markers, including C-reactive protein (CRP) and ferritin, were greatly elevated in all 16 patients, and D-dimer also was elevated.
Treatment, each administered to varying numbers of patients, included corticosteroids, intravenous immunoglobulin, and tocilizumab. Ten patients required intensive care, seven patients received inotropes or vasopressors, three required mechanical ventilation, and one received extracorporeal membrane oxygenation (ECMO). Two of the 16 patients died. An additional 11 patients with illness consistent with MIS-A, but with incomplete information, were identified in three published case series. In one report, all seven patients developed mixed cardiogenic and vasogenic shock. In a second report, both patients had large vessel strokes, and a third report described two patients with endothelitis with associated complement deposition. Overall, eight (30%) of the 27 patients had negative PCR tests but positive antibody tests — a proportion comparable to the 45% reported in MIS-C.
This CDC study suggests that a syndrome quite similar to MIS-C, which by definition was limited to those younger than 21 years of age, also may occur in adults and which they have called MIS-A. In contrast to the frequent presence of severe respiratory abnormalities in MIS-C, however, adults with such findings were excluded from MIS-A to distinguish this group from those who simply had severe COVID-19 or whose extrapulmonary multi-organ dysfunction was caused by hypoxemia, at least in part.
The fact that the SARS-CoV-2 test is negative in the majority of cases of MIS-A, with the remainder being seropositive, suggests that it may result from immunologic/inflammatory post-infectious mechanisms. Of note is that in patients who reported a prior episode of “typical” COVID-19 symptoms, the interval to the development of MIS-A was two to five weeks. The pathologic mechanisms may result in many tissue injuries, including, e.g., endothelial damage and procoagulant effects.
Morris and colleagues indicated that both virologic and antibody testing should be performed in suspected cases. Fortunately, 24 of 27 of the patients described by this group survived, despite their complex and severe disease. The anti-inflammatory treatment they received seems reasonable, but whether it is effective remains undetermined.
Multisystem inflammatory syndrome in adults (MIS-A), similar to multisystem inflammatory syndrome in children (MIS-C), is described by the Centers for Disease Control and Prevention.
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