The emerging threat of multisystem inflammatory syndrome in adults (MIS-A) in COVID-19: A systematic review

Abstract

Background: The exact prevalence of Multisystem Inflammatory Syndrome in Adults (MIS-A) is largely unknown. Vague and multiple definitions and treatment options often add to the confusion on how to label the diagnosis with certainty.

Objectives: The objective of the study was to determine the demographic profile, clinical presentation, laboratory findings and outcomes of MIS-A in COVID-19.

Methods: A systematic review was conducted after registering with PROSPERO. Multiple databases were systematically searched to encompass studies characterizing MIS-A from 1st January 2020 up to 31st August 2021. The inclusion criteria were- to incorporate all published or in press peer-reviewed articles reporting cases of MIS-A. We accepted the following types of studies: case reports, case-control, case series, cross-sectional studies and letters to the editors that incorporated clinical, laboratory, imaging, as well as the hospital course of MIS-A patients. The exclusion criteria for the review were- articles not in English, only abstracts published, no data on MIS-A and articles which have focus on COVID-19, and not MIS-A. Two independent authors screened the articles, extracted the data, and assessed the risk of bias.

Results: A total of 53 articles were included in this review with a sample size of 79 cases. Majority of the patients were males (73.4%) with mean age of 31.67±10.02 years. Fever (100%) and skin rash (57.8%) were the two most common presenting symptoms. Echocardiographic data was available for 73 patients of whom 41 (73.2%) had reduced left ventricular ejection fraction. Cardiovascular system was most frequently involved (81%) followed by gastrointestinal (73.4%) and mucocutaneous (51.9%) involvement. Anti-inflammatory therapies used in treatment included steroids (60.2%), intravenous immunoglobulin (37.2%) and biologics (10.2%). Mean duration of the hospital stay was 11.67±8.08 days. Data regarding the outcomes was available for all 79 subjects of whom 4 (5.1%) died during course of hospital stay.

Conclusions: Emergence of MIS-A calls for further large-scale studies to establish standard case definitions and definite treatment guidelines.

Keywords: Adult; COVID-19; Multisystem inflammatory syndrome; Steroids.

Fig. 1

Figure highlighting the pathophysiology of MIS-A. SARS-CoV-2 infection is characterized by an inflammatory immune response comprising both the innate as well as the adaptive immune system leading to recovery in majority of cases. However, in a fraction of cases following recovery, there develops a dysregulated immune response leading to a hyperinflammatory phase characterized by macrophage activation which leads to activation of innate as well as adaptive immune system comprising B-cells and T-cells with the production of inflammatory cytokines as well as antibodies. These inflammatory cytokines lead to multisystem inflammatory response and development of MIS-A. The exact cause for the dysregulated immune response following recovery is not known however, has been speculated to be due to super antigens or persistent viral antigens or even autoantibodies. Figure created by Biorender.com. * Altered sensorium implies decreased consciousness, altered mental status, altered awareness or confusion.

Fig. 2

PRISMA flow diagram of the systematic review.