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Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID‐19 patients
Author(s) -
Mitamura Yasutaka,
Schulz Daniel,
Oro Saskia,
Li Nick,
Kolm Isabel,
Lang Claudia,
Ziadlou Reihane,
Tan Ge,
Bodenmiller Bernd,
Steiger Peter,
Marzano Angelo,
Prost Nicolas,
Caudin Olivier,
Levesque Mitchell,
Stoffel Corinne,
SchmidGrendelmeier Peter,
Maverakis Emanual,
Akdis Cezmi A.,
Brüggen MarieCharlotte
Publication year - 2022
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.14983
Subject(s) - medicine , immunology , cytotoxic t cell , cytokine storm , skin biopsy , biology , pathology , biopsy , infectious disease (medical specialty) , disease , covid-19 , biochemistry , in vitro
Background Coronavirus disease‐2019 (COVID‐19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID‐19 may impact the development of the MDR. Methods Blood and skin samples from COVID‐19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID‐MDR), healthy controls, non‐COVID‐19—related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high‐throughput multiplexed proteomic profiling of serum were performed. Results IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8 + T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID‐MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID‐MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID‐MDR patients revealed upregulation of various inflammatory mediators (IL‐4, IL‐5, IL‐6, TNF, and IFN‐γ), eosinophil and Mo/Mac ‐attracting chemokines (MCP‐2, MCP‐3, MCP‐4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID‐MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features. Conclusion A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8 + T cells in severe COVID‐19 patients, which in turn may impact the development of MDR.