Swiss Institute for Allergy Research (SIAF) Davos, Davos, Switzerland.
Institute for Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Allergy. 2022 Feb;77(2):595-608. doi: 10.1111/all.14983. Epub 2021 Jul 19.
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.
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.
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.
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.
新型冠状病毒病 2019（COVID-19）与皮肤表现有关，其中一些是药物过敏反应的结果，如斑丘疹性药物疹（MDR）。本研究旨在探讨 COVID-19 是否会影响 MDR 的发生。
分析 COVID-19 患者（基于鼻咽 PCR 阳性）中 COVID-MDR、健康对照者、非 COVID-19 相关药物性皮疹伴嗜酸性粒细胞增多和全身症状（DRESS）和 MDR 患者的血液和皮肤样本。我们利用成像质谱细胞术（IMC）对皮肤活检中的细胞浸润进行了特征分析。此外，还对皮肤活检样本进行了 RNA 测序转录组分析和血清高通量多指标蛋白组学分析。
聚类分析显示，COVID-MDR 中更显著、表型转移的细胞毒性 CD8 T 细胞群和高度激活的单核细胞/巨噬细胞（Mo/Mac）簇。RNA 测序转录组显示 COVID-MDR 皮肤中有更强的细胞毒性反应。然而，在 MDR 诊断时，并未在皮肤活检中检测到严重急性呼吸综合征冠状病毒 2。COVID-MDR 患者的血清蛋白质组学分析显示，各种炎症介质（IL-4、IL-5、IL-6、TNF 和 IFN-γ）、嗜酸性粒细胞和 Mo/Mac 趋化因子（MCP-2、MCP-3、MCP-4 和 CCL11）上调。与 DRESS 中观察到的相对较轻的细胞因子风暴相比，蛋白质组学分析显示 COVID-MDR 中存在大量系统性细胞因子风暴，而 MDR 则没有表现出这些特征。
全身性细胞因子风暴可能会促进重症 COVID-19 患者中 Mo/Mac 和细胞毒性 CD8 T 细胞的激活，进而可能影响 MDR 的发生。
