The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery

Eleni Syrimi ,Eslam Al‐Abadi ,Pavle Vrljicak ,Wioleta M Zelek ,S Welch ,Prasad Nagakumar ,Pamela Kearns ,Sean Monaghan ,Scott Hackett ,Paul G Murray ,Barnaby R Scholefield ,Éanna Fennell ,Ashish Chikermane ,Naeem Khan ,Richard Stark ,Alex Richter ,Sian Faustini ,Pamela Dawson ,Hari Krishnan Kanthimathinathan ,Deepthi Jyothish ,Kate Davies ,Sascha Ott ,Graham S Taylor

doi:10.1016/j.isci.2021.103215

Abstract

SummaryMultisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease.

Highlights

Infection of children with SARS-CoV-2, the viral cause of coronavirus disease 2019 (COVID-19) is associated with two distinct outcomes
Plasma profiling identified multiple features shared by Multisystem inflammatory syndrome in children (MIS-C), Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or Tumor Necrosis Factor alpha (TNF-a)
We identified several potential mechanisms of action for intravenous immunoglobulin (IVIG), the most commonly used drug to treat MIS-C

Summary

Introduction

Infection of children with SARS-CoV-2, the viral cause of coronavirus disease 2019 (COVID-19) is associated with two distinct outcomes. Several weeks after the primary infection, children with MIS-C present with fever, inflammation and evidence of single or multi-organ failure that manifests with cardiac dysfunction, hypotension and life-threatening shock. This is accompanied by lymphopaenia and neutrophilia, both of which are rare in acute pediatric COVID-19 (Ahmed et al, 2020; Castagnoli et al, 2020; Hoang et al, 2020; Kanthimathinathan and Scholefield, 2020; Hoste et al, 2021). MIS-C shares features with KD there are

Results

Discussion

Conclusion