Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases including rheumatoid arthritis (RA), Crohn disease (CD), ulcerative colitis (UC), lupus, and interstitial lung disease. Our cross-disease analysis revealed that an FCN1+ inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10+ CCL2+ inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1, and IL1B. We found that the CXCL10+ CCL2+ macrophages are transcriptionally similar to blood-derived macrophages stimulated with TNF-α and IFN-γ ex vivo. Our findings suggest that IFN-γ, alongside TNF-α, might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases, which may be targeted by existing immunomodulatory therapies.

中文翻译：

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IFN-γ 和 TNF-α 驱动 CXCL10 + CCL2 + 巨噬细胞表型在严重的 COVID-19 和其他组织炎症疾病中扩大。

免疫抑制和抗细胞因子治疗可能对 COVID-19 患者有保护作用。通过已建立的疗法了解 COVID-19 和其他炎症性疾病之间共享的免疫细胞状态可能有助于指定免疫调节疗法。使用综合策略，我们通过荟萃分析来自 COVID-19 和 5 种炎症性疾病（包括类风湿性关节炎 (RA)、克罗恩病 (CD)、溃疡性结肠炎 (UC)、狼疮和间质性肺病）的 > 300,000 个免疫细胞建立了参考. 我们的跨疾病分析显示 FCN1+ 炎性巨噬细胞状态在 COVID-19 支气管肺泡灌洗样本、RA 滑膜、CD 回肠和 UC 结肠中很常见。我们还观察到，在严重的 COVID-19、发炎的 CD 和 RA 中，CXCL10+ CCL2+ 炎性巨噬细胞状态丰富，并表达炎症基因，如 GBP1、STAT1 和 IL1B。我们发现 CXCL10+ CCL2+ 巨噬细胞在转录上与体外用 TNF-α 和 IFN-γ 刺激的血液来源的巨噬细胞相似。我们的研究结果表明，在严重的 COVID-19 和其他炎症性疾病中，IFN-γ 与 TNF-α 可能是这种丰富的炎性巨噬细胞表型的关键驱动因素，这些疾病可能是现有免疫调节疗法的目标。