PMC9995372_01
COVID-19 associated Multisystem Inflammatory Syndrome of Adults (MIS-A) is associated with critical illness, cytokine dysregulation and altered immune cell landscape. (A) MIS-A case outlining timeline of prior mild COVID-19 upper respiratory tract infection (URTI) and subsequent presentation of critical illness due to MIS-A with symptoms, treatments, and investigational sampling times (T=1 and T=2) highlighted. (B) A multi-disciplinary pre-existing COVID-19 investigational approach was utilized to investigate immune responses in this rare syndrome with relevant healthy and recovered COVID-19 controls. (C) Multiplex cytokine arrays (i) defined upregulated and down regulated cytokines, notably IL-10 and IP-10, and soluble cytokine receptors (ii) including sCD25 (IL2alphaR) as key markers of cytokine storm. (D) Single cell RNA seq (scRNAseq) immune cell annotation using the Azimuth database (i) with identification of cellular source (ii) identifying increased B cell and neutrophil populations in MIS-A.
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On exam he was noted to have a macular blanching skin rash on his torso and proximal extremities, bilateral non-purulent conjunctivitis, sore throat, and prominent non-exertional chest pressure associated with progressive shortness of breath ( Figure 1A ). In the emergency department he was febrile, hypotensive due to cardiogenic shock, and started on vasopressors to maintain systolic blood pressure and was eventually transferred to the Cardiac Care Unit (CCU) for cardiac support ( Figure 1A ,  Supplementary Table 1 ). An initial chest Computed Tomography (CT) scan using a pulmonary embolism protocol was negative with remarkably normal lungs ( Figure 1A ). Eventually while still in CCU he had an indium white blood scan that did not show any active infection or inflammation (Supplementary  Figure 1 ). A repeat echocardiogram prior to discharge showed normal right and left ventricular function which was corroborated by cardiac MRI showing no signs of myocarditis (Supplementary  Figure 1 ).