key: cord-0688709-qxp31jlu
authors: Tonon, D; Landrieux, C; Van Den Plas, S; Harlé, JR; Lepidi, H; Bourenne, J; Jaussaud, N; Lagier, D
title: Multisystem inflammatory syndrome-related refractory cardiogenic shock in adults after COVID-19 infection: a case series
date: 2022-03-18
journal: Eur Heart J Case Rep
DOI: 10.1093/ehjcr/ytac112
sha: 5fa179514142c65d8bfe4830e90842174628f9ea
doc_id: 688709
cord_uid: qxp31jlu

BACKGROUND: A novel multisystem inflammatory syndrome in children (MIS-C) temporally associated with the coronavirus disease 2019 (COVID-19) infection has been reported, arising weeks after the peak incidence of COVID-19 infection in adults. Patients with MIS-C have been reported to have cardiac involvement and clinical features overlapping with other acute inflammatory syndromes such as Kawasaki-Disease, toxic shock syndrome, and macrophage activation syndrome. MIS-C may follow Covid-19 infection, most of the time after its asymptomatic form, even though it can lead to serious and life-threatening illness. CASE SUMMARY: In this case series, we discuss two cases of young adults with no former medical history who fit with the criteria defined in MIS-C. They both developed a refractory cardiogenic shock and required intensive care treatment including mechanical circulatory support, specifically the use of venous-arterial extracorporeal membrane oxygenation (VA-ECMO). They were both treated early with intravenous immune globulin and adjunctive high-dose steroids. They recovered ad integrum in less than two weeks. DISCUSSION: MIS-C occurs 2 to 4 weeks after infection with SARS-CoV-2. Patients with MIS-C should ideally be managed in an intensive care environment since rapid clinical deterioration may occur. It would be preferable to have a multi-disciplinary care to improve outcomes. Patients should be monitored for shock. Elucidating the mechanism of this new entity may have importance for understanding COVID-19 far beyond the patients who have had MIS-C to date. The pathogenesis seems to involve post-infectious immune dysregulation so early administration intravenous immune globulin associated to corticosteroids appears appropriate. It implies early recognition of the syndrome even in young adults.

Ethics approval and consent to participate : 12 The author/s confirm that written consent for submission and publication of this case series 13 including image(s) and associated text has been obtained from the patient in line with COPE 14

guidelines. 15 This study was approved by the local Ethics Commission (2020-53) and the French Society of 16

Anaesthesia and Critical Care (00010254-2020-06). 17 18

visceral dysfunction, sometimes with refractory heart failure requiring VA ECMO.

This syndrome has been well described in healthy children but in this case it occurs in young adults.

Delayed onset after infection which suggests that the pathogenesis involves post-infectious immune 5 dysregulation.

The majority of affected patients should be treated with intravenous immunoglobulins, and also received 7 adjunctive high-dose steroids.

Early recognition of the syndrome even in young adults is needed for better prognosis. Health Organization. It is well known that the main target of COVID-19 is the pulmonary 4 system. Indeed, severe COVID-19 represents viral pneumonia from severe acute respiratory 5 syndrome coronavirus 2 (SARS-CoV-2) infection leading to acute respiratory distress 6 syndrome (ARDS). Ultimately, in patients with therapy refractory severe ARDS, the application 7 of extracorporeal membrane oxygenation (ECMO) represents a treatment option (1). 8 SARS-CoV-2 induced infection is associated with pulmonary and extra pulmonary 9 manifestations, foremost among which are cardiological lesions with acute myocardial injury, 10 that we report herein (2). It is not clearly understood how COVID-19 compromises the However, recent clinical, microbiological and immunological reports describe MIS-C as a new 24 immunopathogenic disease (9,10,11). According to the different definitions of MIS-C (12) , it 25 appears to be a rare complication occurring only in child population. Evenmore this syndrome 26 begins to be described in adults (13) . Herein we will discuss the special case of two adults with 27 MIS-C syndrome, who all needed organ support by VA ECMO. They had no previous history of COVID-19 symptoms or contact with known COVID-19 cases.

They both describe flu-like syndrome about 3 weeks before their hospitalization. 6 At their admission, (Day 1) they declared exactly similar symptoms including fever during at 7 least 72h, cutaneous and mucosal rash (Fig. 1 a,c) , gastro-intestinal symptoms with pain, 8 diarrhea, nausea and vomiting, uveitis for only one of them (Fig. 1 b) . Then, both patients 9 were rapidly (Day 1) admitted in intensive care unit (ICU) because of hemodynamic failure. All On admission the patients also have severe acute kidney injury KDIGO 2 and hepatic failure 18 associated with a strong biological inflammatory syndrome (Table 1) . 19 In view of multi-visceral involvement and refractory hemodynamic instability, both were 1,5T (Fig. 3 a) and a late gadolinium enhancement pattern (LGE) with 8 pericardial effusion, all related with myo-pericarditis (Fig. 3 b) . An histological analysis of an 9 endomyocardial biopsy realized during coronary angiography for Patient 2 were also 10 suggestive of the diagnosis, showing a diffuse non-specific myocarditis with dense 11 inflammatory cell infiltrate (white arrows) between the cardiomyocytes (Fig. 4 c) , composed 12 mainly with macrophages (Fig. 4 b) , lymphocytes (Fig. 4 a) and neutrophils. Cardiomyocyte 13 damages in the form of nuclear loss (black arrows), eosinophilic cytoplasmic homogenization, 14 or necrosis are present (Fig. 4 c) . On Day 2, for both patients, we introduced a treatment with 15 intravenous immunoglobulin (IVIg) 1g/kg/j for 2 days associated with methylprednisolone 16 2mg/kg per day for 5 days, then progressively decreased. We report a good tolerance with no 17 side effects during treatment. Also, an effective treatment with Unfractionated Heparin (UFH) 18 (target therapeutic range of activated partial thromboplastin time (aPTT) 60s) was conducted 19 on Day 1. The inflammatory syndrome resolved quickly after the initiation of the combination 20 therapy (Fig. 5) . When the weaning trial was hemodynamically well tolerated without the 21 need for increasing inotropic or vasoactive support and echo-cardiographic criteria were The recent emergence of MIS-C explains the lack of randomized trials, and therapeutic 8 management is largely based on knowledge of Kawasaki disease and the suspected 9 pathophysiology of MIS-C. 10 Elucidating the mechanism of this new entity may have importance for understanding Covid- Additional studies could be initiated to confirm the place of this treatment in adults.

To our knowledge this is the third report case of adult MIS-C related to SARS-CoV-2 infection 24 (14, 15), but the first one relating VA ECMO Life Support for refractory cardiogenic shock with 25 favorable outcomes. As it seems to appear in this case report, the MIS-C syndrome, which is now well known in the 2 child population, can also appear in adults. In rare cases, it can even lead to cardiac failure 3 resulting in organ support by VA ECMO. In the light of this fact, this syndrome should be in 

Groupe de Recherche Clinique en 9

REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne 10

Extracorporeal membrane oxygenation for 11 severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study

Coronaviruses and the cardiovascular system: acute and 14 long-term implications

Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic

COVID-19 and mechanical circulatory support

PIMS-TS Study Group and EUCLIDS 4 and PERFORM Consortia. Clinical Characteristics of 58 Children With a Pediatric Inflammatory 5 Multisystem Syndrome Temporally Associated With SARS-CoV-2

Peripheral immunophenotypes in 8 children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection

Inflammatory Syndrome in Children with COVID-19

Paediatric Inflammatory Multisystem Syndrome Temporally-13

Associated with SARS-CoV-2 Infection: An Overview

multisystem inflammatory disease in an adult

Last A; UCLH COVID Response Team. An adult presentation consistent with 18 PIMS-TS

Kawasaki-like Syndrome 20 as an Emerging Complication of SARS-CoV-2 Infection in Young Adults