tetano
Editor, Senior Moderator
iScience
. 2021 Oct 2;103215.
doi: 10.1016/j.isci.2021.103215. Online ahead of print.
The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery
Eleni Syrimi[SUP] 1 [/SUP], Eanna Fennell[SUP] 2 [/SUP], Alex Richter[SUP] 3 [/SUP], Pavle Vrljicak[SUP] 4 [/SUP], Richard Stark[SUP] 5 [/SUP], Sascha Ott[SUP] 4 5 [/SUP], Paul G Murray[SUP] 1 2 [/SUP], Eslam Al-Abadi[SUP] 6 [/SUP], Ashish Chikermane[SUP] 6 [/SUP], Pamela Dawson[SUP] 6 [/SUP], Scott Hackett[SUP] 7 [/SUP], Deepthi Jyothish[SUP] 6 [/SUP], Hari Krishnan Kanthimathinathan[SUP] 6 [/SUP], Sean Monaghan[SUP] 6 [/SUP], Prasad Nagakumar[SUP] 6 8 [/SUP], Barnaby R Scholefield[SUP] 6 8 [/SUP], Steven Welch[SUP] 7 [/SUP], Naeem Khan[SUP] 3 [/SUP], Sian Faustini[SUP] 3 [/SUP], Kate Davies[SUP] 9 [/SUP], Wioleta M Zelek[SUP] 9 [/SUP], Pamela Kearns[SUP] 10 [/SUP], Graham S Taylor[SUP] 1 [/SUP]
Affiliations
Abstract
Multisystem 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; 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 IL6 may be preferable to IL1 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.
. 2021 Oct 2;103215.
doi: 10.1016/j.isci.2021.103215. Online ahead of print.
The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery
Eleni Syrimi[SUP] 1 [/SUP], Eanna Fennell[SUP] 2 [/SUP], Alex Richter[SUP] 3 [/SUP], Pavle Vrljicak[SUP] 4 [/SUP], Richard Stark[SUP] 5 [/SUP], Sascha Ott[SUP] 4 5 [/SUP], Paul G Murray[SUP] 1 2 [/SUP], Eslam Al-Abadi[SUP] 6 [/SUP], Ashish Chikermane[SUP] 6 [/SUP], Pamela Dawson[SUP] 6 [/SUP], Scott Hackett[SUP] 7 [/SUP], Deepthi Jyothish[SUP] 6 [/SUP], Hari Krishnan Kanthimathinathan[SUP] 6 [/SUP], Sean Monaghan[SUP] 6 [/SUP], Prasad Nagakumar[SUP] 6 8 [/SUP], Barnaby R Scholefield[SUP] 6 8 [/SUP], Steven Welch[SUP] 7 [/SUP], Naeem Khan[SUP] 3 [/SUP], Sian Faustini[SUP] 3 [/SUP], Kate Davies[SUP] 9 [/SUP], Wioleta M Zelek[SUP] 9 [/SUP], Pamela Kearns[SUP] 10 [/SUP], Graham S Taylor[SUP] 1 [/SUP]
Affiliations
- PMID: 34632327
- PMCID: PMC8487319
- DOI: 10.1016/j.isci.2021.103215
Abstract
Multisystem 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; 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 IL6 may be preferable to IL1 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.