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Reviews of "Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children"

Reviewers: Moshe Arditi, Magali Noval Rivas, Rebecca A. Porritt (Cedars-Sinai Medical Center) | 📒📒📒◻️◻️ • Ashraf Harahsheh, Vanessa Bundy (Children's National Hospital) | 📙📙 ◻️◻️◻️ • Paolo Palma (Bambino Gesù Children's Hospital) | 📕 ◻️◻️◻️◻️

Published onNov 22, 2020
Reviews of "Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children"
key-enterThis Pub is a Review of
Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8+ T-cells and CD56dimCD57+ NK cells. Bayesian network analyses revealed nine key regulators of this module, including TBX21, a central coordinator of exhausted CD8+ T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.

To read the original manuscript, click the link above.

Summary of Reviews: This study compares transcriptomes from patients afflicted with MIS-C, a condition resulting from COVID-19, with other pediatric disorders and finds MIS-C shares a similar molecular etiology to Kawasaki Disease. Reviewers found the claims unsubstantiated and greatly misleading.

Reviewer 1 (Moshe Arditi, Magali Noval Rivas, Rebecca A. Porritt) | 📒📒📒 ◻️◻️

Reviewer 2 (Ashraf Harahsheh, Vanessa Bundy) | 📙📙 ◻️◻️◻️

Reviewer 3 (Paolo Palma) | 📕 ◻️◻️◻️◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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