loading page

Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID-19 patients
  • +16
  • yasutaka mitamura,
  • Daniel Schulz,
  • Saskia Oro,
  • Nick Li,
  • Isabel Kolm-Djamei,
  • Claudia Lang,
  • Reihane Ziadlou,
  • Ge Tan,
  • Bernd Bodenmiller,
  • Peter Steiger,
  • Angelo Marzano,
  • Nicola de Prost ,
  • Olivier Caudin ,
  • Mitchell Levesque ,
  • Corinne Stoffel ,
  • Peter Schmid-Grendelmeier,
  • Emanual Maverakis ,
  • Cezmi Akdis,
  • Marie-Charlotte Brüggen
yasutaka mitamura
University of Zurich Swiss Institute of Allergy & Asthma Research
Author Profile
Daniel Schulz
University of Zurich
Author Profile
Saskia Oro
Hospital Henri Mondor
Author Profile
Nick Li
University Hospital Zurich
Author Profile
Isabel Kolm-Djamei
University of Zurich
Author Profile
Claudia Lang
University Hospital Zurich
Author Profile
Reihane Ziadlou
University Hospital Zurich
Author Profile
Ge Tan
University of Zurich
Author Profile
Bernd Bodenmiller
University of Zurich
Author Profile
Peter Steiger
University of Zurich
Author Profile
Angelo Marzano
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Author Profile
Nicola de Prost
Hospital Henri Mondor
Author Profile
Olivier Caudin
Hospital Henri Mondor
Author Profile
Mitchell Levesque
University Hospital Zurich
Author Profile
Corinne Stoffel
University Hospital Zurich
Author Profile
Peter Schmid-Grendelmeier
University Hospital Zurich
Author Profile
Emanual Maverakis
University of California Davis
Author Profile
Cezmi Akdis
University of Zurich
Author Profile
Marie-Charlotte Brüggen
University Hospital Zurich
Author Profile

Abstract

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 is associated with the development of the MDR. Method Blood and skin samples from COVID-19 patients suffering from maculopapular drug rashes (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 (SARS-CoV-2) was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed up-regulation of various inflammatory mediators (IL-4, IL-5, IL-6, IL-8, IL-18, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Analyses of cytokine networks demonstrated a relatively milder cytokine storm in DRESS compared to COVID-MDR, while MDR did not exhibit such features. Conclusion A massive 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.

Peer review status:ACCEPTED

20 Feb 2021Submitted to Allergy
23 Feb 2021Submission Checks Completed
23 Feb 2021Assigned to Editor
23 Feb 2021Reviewer(s) Assigned
08 Mar 2021Review(s) Completed, Editorial Evaluation Pending
09 Mar 2021Editorial Decision: Revise Minor
03 May 20211st Revision Received
04 May 2021Assigned to Editor
04 May 2021Submission Checks Completed
04 May 2021Reviewer(s) Assigned
17 May 2021Review(s) Completed, Editorial Evaluation Pending
17 May 2021Editorial Decision: Revise Minor
03 Jun 20212nd Revision Received
04 Jun 2021Submission Checks Completed
04 Jun 2021Assigned to Editor
04 Jun 2021Reviewer(s) Assigned
10 Jun 2021Review(s) Completed, Editorial Evaluation Pending
10 Jun 2021Editorial Decision: Accept