Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in severely ill COVID‐19 patients

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 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.

Bullous pemphigoid in a young male after COVID‐19 mRNA vaccine: a report and brief literature review

“…4,9 A recent study showed that MPE observed in these COVID-19 patients could be favoured by the systemic cytokine storm promoting activation of monocytes/macrophages and eosinophils chemokines and cytotoxic CD8 + T cells. 10 Our study reinforces this hypothesis that SARS-CoV-2 infection could trigger DH by a particular pathophysiological mechanism that could involve eosinophils.…”

High frequency of eosinophilia and viral reactivation in drug hypersensitivity in patients with severe acute respiratory syndrome coronavirus 2 infection

“…4,9 A recent study showed that MPE observed in these COVID-19 patients could be favoured by the systemic cytokine storm promoting activation of monocytes/macrophages and eosinophils chemokines and cytotoxic CD8 + T cells. 10 Our study reinforces this hypothesis that SARS-CoV-2 infection could trigger DH by a particular pathophysiological mechanism that could involve eosinophils.…”

The effect of allergy and asthma as a comorbidity on the susceptibility and outcomes of COVID-19

“…Sixteen COVID-19 patients with a self-reported history of DA have been reported in our 140 cases ( 26 ). A systemic cytokine storm was suggested to promote activation of monocytes, macrophage and cytotoxic CD8 + T cells in severe COVID-19 patients, which in turn may impact the development of maculopapular drug rashes (MDR) ( 120 ). Skin biopsies might be necessary to differentiate viral exanthem from drug-induced exanthem in COVID-19 patients ( 121 ).…”

“…Skin biopsies might be necessary to differentiate viral exanthem from drug-induced exanthem in COVID-19 patients ( 121 ). No SARS-CoV-2 was detected in skin biopsies of MDR in COVID-19 patients ( 120 ). However, to the best of our knowledge, there are no reports on the expression of ACE2 and other SARS-CoV-2 receptors in DA patients, and the outcome of COVID-19 patients with DA.…”