MIS-A: A Severe Inflammatory Syndrome in Adults After COVID-19 Infection, 2020

Early in the COVID-19 pandemic, doctors in Europe and the United States began reporting a new condition in children: multisystem inflammatory syndrome in children (MIS-C), a rare but severe illness with shock, heart problems, abdominal pain and very high inflammation markers. From June 2020, reports described a similar syndrome in adults. In October 2020, CDC reviewed 27 such cases and called the illness multisystem inflammatory syndrome in adults (MIS-A).

How MIS-A was defined

A patient had to meet five working criteria:

1. a severe illness requiring hospitalization, aged 21 or older
2. a positive test for current or past SARS-CoV-2 infection — PCR, antigen or antibody — during admission or in the previous 12 weeks
3. severe dysfunction of one or more organ systems outside the lungs — such as shock, heart dysfunction, blood clots or acute liver injury
4. laboratory evidence of severe inflammation
5. no severe respiratory illness, to separate MIS-A from severe COVID-19

The 27 cases came from 9 patients reported to CDC, 7 published case reports, and 11 patients in 3 published case series.

The 16 detailed cases

The patients reported to CDC and in single case reports, from seven U.S. jurisdictions and the United Kingdom, were aged 21 to 50: seven men and nine women. Nine had no known underlying conditions; six had obesity.

• 12 had fever when they arrived; all 16 showed heart involvement — arrhythmias, raised troponin or weakened heart function on ultrasound.
• 13 had gastrointestinal symptoms and 5 had skin or mucous-membrane signs.
• Despite few breathing symptoms, 10 had ground-glass shadows and 6 had fluid around the lungs on imaging.
• Inflammation markers were very high in all — C-reactive protein peaking at 84–580 mg/L (normal under 10).
• Only half (8) had any documented respiratory illness beforehand; in those who did, MIS-A came approximately 2–5 weeks later.

Testing: 10 had a positive PCR test when first assessed; of 6 with a negative PCR, 4 had positive antibody tests.

Treatment and outcomes: 7 received intravenous immunoglobulin, 10 corticosteroids and 2 tocilizumab. 10 needed intensive care, 7 drugs to support blood pressure or the heart, 1 mechanical circulatory support, and 3 mechanical ventilation. Two died.

The case series

• Seven previously healthy young men, aged 20–42, with shock from heart failure and blood-vessel dilation, very high inflammation and high antibody levels; four had negative PCR tests. All needed heart-support drugs, three needed balloon pumps, and all seven recovered after 7–18 days in hospital.
• Two patients, aged 21 and 50, with large-vessel strokes and minimal respiratory symptoms; such strokes in young adults had been significantly less common in the same period a year earlier.
• Two patients with heart problems, abdominal symptoms and rash whose tissues showed inflamed blood-vessel linings; one recovered and one, with several underlying conditions, died within hours.

What it means

• 24 of 27 patients survived, with hospital, often intensive, care.
• 8 of 27 (30%) had negative PCR but positive antibody tests — as did 45% of 440 children with MIS-C — suggesting both syndromes may often follow infection rather than accompany it, though persistent infection outside the airways is possible. The cause is unknown.
• Clinicians should consider MIS-A in adults with matching signs, use antibody testing when PCR or antigen tests are negative, and check a panel of inflammation, clotting and organ-damage markers.
• All but one of the patients whose race or ethnicity was reported belonged to racial or ethnic minority groups, in line with long-standing inequities that raise COVID-19 risk in communities of color — but this small, voluntary sample cannot show the true burden, and better race and ethnicity data are needed.
• Preventing COVID-19 is the surest way to prevent MIS-A.

Limits: the cases were voluntarily reported or published and may not reflect the full picture; excluding severe respiratory illness may miss overlapping cases; and the working definition may sweep in other diseases.

Sources

Based on 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 Vol. 69, No. 40, CDC; a work of the United States government in the public domain.