key: cord-0814680-14d8n0j1
authors: Kerkerian, Geneviève; Vaughan, Stephen D.
title: Multisystem inflammatory syndrome in an adult after SARS-CoV-2 infection
date: 2021-06-21
journal: CMAJ
DOI: 10.1503/cmaj.210232
sha: f091bd7d664a3db2791f56d36370871b59d5440a
doc_id: 814680
cord_uid: 14d8n0j1

nan

• Elevated inflammatory markers support the diagnosis. • Prompt initiation of therapy with immunomodulatory treatment can prevent severe outcomes. The patient was admitted and started on empirical piperacillintazobactam for possible bacterial pneumonia as a superinfection of his previous SARS-CoV-2 infection. Initial laboratory workup was notable for elevated C-reactive protein, D dimer, ferritin and leukocytosis with neutrophilia (Table 1 1 ), indicating acute inflammation. His troponin level was elevated, and he had a substantially elevated pro-brain-type natriuretic peptide level. Blood cultures, urine culture and a respiratory viral panel were drawn and later returned negative. The patient also tested negative for HIV and hepatitis C and was immune to hepatitis B. An autoimmune workup collected before initiation of therapy was negative. COVID-19 immunoglobulin G serology was positive. A transthoracic echocardiogram, done after initiation of corticosteroids, showed normal sinus rhythm and normal right and left ventricular systolic and diastolic function with mild to moderate mitral regurgitation. There were no previous echocardiogram studies with which to compare these findings.

Given the patient's recent history of SARS-CoV-2 infection, fevers without localizing symptoms, oral mucosal changes, cervical lymphadenopathy, conjunctivitis and lower extremity changes, we suspected inflammatory post-COVID-19 syndrome. The presentation was similar to reported cases of an uncommon but severe complication in children and adolescents infected with SARS-CoV-2, called multisystem inflammatory syndrome in children (MIS-C), as well as to Kawasaki-like illness (Table 2 2-4 ) . Both the pediatric and adult rheumatology teams involved in the patient's care agreed that he met the preliminary Centers for Disease Control and Prevention (CDC) criteria for multisystem inflammatory syndrome in adults (MIS-A) and the criteria for complete Kawasaki disease, and he had multiple features consistent with MIS-C.

We started the patient on acetylsalicylic acid (ASA) and methylprednisolone and discontinued antibiotics. The next day, he received intravenous (IV) immunoglobulin. Within 24 hours of beginning treatment, he reported substantial improvement in his level of energy, shortness of breath and anorexia, with documented resolution of fever, improved conjunctivitis ( Figure 3A ), and decreased erythema of his tongue ( Figure 3B ), as well as reduction in inflammatory markers (Table 1) . Repeat electrocardiogram was normal ( Figure 4 ). The patient was discharged home 5 days after admission. Fourteen days after discharge, and again at a 6-week follow-up, he continued to improve clinically and biochemically (Table 1 ).

Since the beginning of the SARS-CoV-2 pandemic, new information has been emerging on the trajectory of the disease. Examples of complications include venous thromboembolism, cardiovascular disease, acute kidney or liver injury, neurologic symptoms and post-COVID-19 syndrome. 5 Multisystem inflammatory syndrome in children was first described in April 2020 as a hyperinflammatory syndrome with features resembling Kawasaki disease. 2,3,6 As of May 3, 2021, 3742 children in the United States had been formally diagnosed with MIS-C according to the criteria outlined in Table 2 , with 35 related deaths. 7 In October 2020, the CDC published a review of 27 adult cases that fit the description of a multisystem inflammatory syndrome. 4 The preliminary case definition of MIS-A is shown in Table 2 , and cases described to date have been in patients younger than 50 years. As we continue to learn about MIS-A, however, it is prudent not to assume any age limitation when considering the diagnosis, as our case suggests. 4,8-10 Many questions about MIS-A remain unanswered. Our patient did not present with the more commonly reported symptoms of stroke, shock or cardiac dysfunction requiring management in the intensive care unit. 4 This may be explained by our patient having a milder spectrum illness or by the prompt diagnosis and interventions he received. Several features of our patient's presentation raised early concern for MIS-A or a Kawasaki-like illness. Our patient met the diagnostic criteria for complete Kawasaki disease (5 d of fever and 4 out of 5 clinical features: extremity changes, conjunctivitis, oral changes and cervical lymphadenopathy; our patient did not have a rash) and MIS-C (except for age). However, evidence of recent SARS-CoV-2 infection and the age of the patient made MIS-A more likely as the cause. The American College of Rheumatology published a review comparing and contrasting features between MIS-C and Kawasaki disease, and it reported that about 25%-50% of patients who fulfilled criteria for MIS-C also met the full diagnostic criteria for Kawasaki disease. 11 Two differences between the conditions were ethnic distribution (highest among people of Japanese descent in patients with Kawasaki disease) and age distribution (usually younger than 5 yr for Kawasaki disease, and a broader range, from 3 months to 21 yr, for MIS-C). 2, 11, 12 Standardized treatment for MIS-A is yet to be established. Our patient improved with 3 days of methylprednisolone 125 mg/d, then an oral prednisone taper of 50 mg/d for 3 days, followed by a tapering dose decreasing by 10 mg/d every 3 days until he was weaned off steroids (for a total oral course of 15 d). He received IV immunoglobulin 1 g/kg/d for 2 days and oral ASA 325 mg/d until clinical resolution, as evidenced by absence of fevers and normal C-reactive protein. This treatment was based on expert opinion and up-to-date evidence on Kawasaki disease and MIS-C. 2, 6, 8, [11] [12] [13] The American College of Rheumatology recommends a step-wise approach to immunomodulatory treatment in MIS-C with IV immunoglobulin or glucocorticoids considered as first-tier agents, 11 and the American Heart Association recommends high-dose immunoglobulin (2 g/kg) as a single IV dose for treatment of Kawasaki disease. 2 Although the patient did not have clinically significant thrombocytosis, we prescribed a short course of high-dose ASA to prevent thrombosis and coronary artery aneurysms. 11 The optimal follow-up for MIS-A is currently unknown, but experts support monitoring for coronary artery dilatation and aneurysm, as with MIS-C-or Kawasaki-like illness. 2, 11 Unlike in children, for whom echocardiography is the imaging choice for coronary artery diameter, the visualization of coronary arteries becomes progressively more difficult as body size increases, making CT coronary angiography preferred for surveillance in adults. 2 Our patient's coronary angiogram showed triple-vessel coronary artery disease without clinically important stenosis and no coronary aneurysms or findings suggestive of coronary artery vasculitis. At time of writing, a repeat CT to visualize coron ary artery calibre is still pending for 6 months after discharge.

Unlike for MIS-C, there is currently no requirement to report cases of MIS-A to provincial or state authorities, but this should be encouraged to facilitate research and improve patient outcomes. 6 

An overview of cycle threshold values and their role in SARS-CoV-2 real-time PCR test interpretation. Toronto: Queen's Printer for Ontario

American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Epidemiology and Prevention. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association

Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C)

Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 Infection -United Kingdom and United States

BMJ Best Practice: Coronavirus diseases 2019 (COVID-19)

Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City

Health department-reported cases of multisystem inflammatory syndrome in children (MIS-C) in the United States

A young adult with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)-like illness: a case report

An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19

A case of multisystem inflammatory syndrome post-COVID-19 infection in an adult

American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: version 1

Kawasaki disease in adults: report of 10 cases

Pediatric inflammatory multisystem syndrome temporally associated with COVID-19: a spectrum of diseases with many names

The authors acknowledge Drs. Glen Hazlewood, Heinrike Schmeling and Kevin Fonseca for their expert opinion in the management of this case.

This article has been peer reviewed.The authors have obtained patient consent.Affiliation: Division of Infectious Diseases, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alta.

Both authors contributed to the conception and design of the work, drafted the manuscript, revised it critically for important intellectual content, gave final approval of the version to be published and agreed to be accountable for all aspects of the work.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/ Correspondence to: Geneviève Kerkerian, genevieve.kerkerian@albertahealthservices.caThe section Cases presents brief case reports that convey clear, practical lessons. Preference is given to common presentations of important rare conditions, and important unusual presentations of common problems. Articles start with a case presentation (500 words maximum), and a discussion of the underlying condition follows (1000 words maximum). Visual elements (e.g., tables of the differential diagnosis, clinical features or diagnostic approach) are encouraged. Consent from patients for publication of their story is a necessity. See information for authors at www.cmaj.ca.