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Multisystem inflammatory syndrome in adults
Other Resources UpToDate PubMed

Multisystem inflammatory syndrome in adults

Contributors: Paritosh Prasad MD, Eric Ingerowski MD, FAAP
Other Resources UpToDate PubMed


A multisystem inflammatory disorder was identified during the coronavirus disease 2019 (COVID-19) pandemic called multisystem inflammatory syndrome in children (MIS-C) that primarily affects children and presents with some combination of shock, cardiac dysfunction, abdominal pain, and elevated inflammatory markers.

Since June 2020, similar case reports have been reported in adults, leading to the description of a clinical disorder named multisystem inflammatory syndrome in adults, or MIS-A. Onset is days to weeks following COVID-19 illness from SARS-CoV-2 infection.

According to the US Centers for Disease Control and Prevention (CDC), the case definition is as follows.

A patient aged ≥ 21 years hospitalized for ≥ 24 hours, or with an illness resulting in death, who meets the following clinical and laboratory criteria. The patient should not have a more likely alternative diagnosis for the illness (eg, bacterial sepsis, exacerbation of a chronic medical condition).

Clinical Criteria
Subjective fever or documented fever (≥ 38.0°C) for ≥ 24 hours prior to hospitalization or within the first THREE days of hospitalization* and at least THREE of the following clinical criteria occurring prior to hospitalization or within the first THREE days of hospitalization.* At least ONE must be a primary clinical criterion.

Primary clinical criteria:
  1. Severe cardiac illness (includes myocarditis, pericarditis, coronary artery dilatation / aneurysm, or new-onset right or left ventricular dysfunction [LVEF < 50%], 2nd/3rd degree A-V block, or ventricular tachycardia) (Note: cardiac arrest alone does not meet this criterion)
  2. Rash AND nonpurulent conjunctivitis
Secondary clinical criteria:
  1. New-onset neurologic signs and symptoms (includes encephalopathy in a patient without prior cognitive impairment, seizures, meningeal signs, or peripheral neuropathy) (including Guillain-Barré syndrome)
  2. Shock or hypotension not attributable to medical therapy (eg, sedation, renal replacement therapy)
  3. Abdominal pain, vomiting, or diarrhea
  4. Thrombocytopenia (platelet count < 150 000/microliter)
Laboratory evidence – The presence of laboratory evidence of inflammation AND SARS-CoV-2 infection:
  • Elevated levels of at least TWO of the following: C-reactive protein (CRP), ferritin, interleukin (IL)-6, erythrocyte sedimentation rate (ESR), procalcitonin
  • A positive SARS-CoV-2 test for current or recent infection by reverse transcription polymerase chain reaction (RT-PCR), serology, or antigen detection
NOTE: *These criteria must be met by the end of hospital day 3, where the date of hospital admission is hospital day 0.

An October 2020 Morbidity and Mortality Weekly Report summarized a total of 16 individual case reports and 3 case series published of patients meeting criteria for MIS-A. These patients were aged 20-50 years, with a roughly equal ratio of men to women (7 men, 9 women) in the individual case reports; 9 of the 16 case report patients were African American, 1 was of African descent born in the United Kingdom, 5 were of Hispanic descent, and 1 was of Asian descent. This was similar to the ethnic breakdown of the one case series that reported ethnicity in which 2 of 7 reported patients were African American, 2 were of Hispanic descent, and 2 were of Middle Eastern descent, with 1 reported as White. About half of the case report patients (9 of 16) had no reported past medical history, 6 were obese, 1 had type 2 diabetes, 2 had hypertension, and 1 had obstructive sleep apnea. One-half of case report patients had a documented respiratory illness prior to developing symptoms of MIS-A, and one-half did not.

Seventy-five percent of case report patients (12 of 16) had fever > 100.4°F (38°C) for over 24 hours or reported subjective fevers for greater than 24 hours upon presentation; 6 of these 16 had chest pain or palpitations, and all 16 had cardiac effects such as cardiac arrhythmias, elevated troponin levels, or echocardiographic evidence of ventricular dysfunction. Thirteen of the sixteen had gastrointestinal symptoms on admission, and 5 had dermatologic findings, 3 of whom had mucositis. While most did not have significant respiratory symptoms, 10 of 16 had ground glass opacities noted on chest CT, and 6 had pleural effusions.

All patients described with MIS-A had elevated inflammatory makers including elevated CRP, ferritin, and D-dimers. Ten of the sixteen were also found to be leukopenic.

With respect to SARS-CoV-2 testing, 10 of the 16 case reports were positive for SARS-CoV-2 by PCR at the time of initial assessment for MIS-A. Of these 10, 7 also had positive SARS-CoV-2 antibody (Ab) testing. Six had negative SARS-CoV-2 PCR, of whom four had positive SARS-CoV-2 Ab testing. Five of the sixteen had documentation of SARS-CoV-2 PCR positivity in the preceding weeks, ranging from 14 to 41 days prior to presentation with MIS-A.

Treatment is largely supportive, although patients have received intravenous (IV) immunoglobulin (IVIG), corticosteroids, or tocilizumab (IL-6 inhibitor). There is very little evidence available to guide the use of these immunomodulatory therapies in MIS-A.

While it is difficult to assess the mortality of the condition given the limited number of published cases, at least 2 of the 16 case report patients ultimately succumbed to the illness.

Related topics: post-COVID conditions, skin and oral mucosal manifestations of COVID-19


M35.81 – Multisystem inflammatory syndrome

1119306006 – Multisystem inflammatory syndrome in adults

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Last Reviewed:03/06/2022
Last Updated:09/26/2023
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Multisystem inflammatory syndrome in adults
A medical illustration showing key findings of Multisystem inflammatory syndrome in adults : Chest pain, Diarrhea, Nausea/vomiting, Diffuse rash
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