SARS-CoV-2 infection can cause severe disease for which currently no specific therapy is available. The use of hydroxychloroquine to prevent or treat SARS-CoV-2 infection is controversial and its mode of action poorly understood. We demonstrate that hydroxychloroquine inhibits trained immunity at the functional and epigenetic level and is accompanied by profound changes in the cellular lipidome as well as reduced expression of interferon-stimulated genes. Trained immunity comprises a functional adaptation induced by epigenetic reprogramming which facilitates the anti-viral innate immune response. Our findings therefore suggest that hydroxychloroquine may not have a beneficial effect on the anti-viral immune response to SARS-CoV-2.

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羟氯喹抑制训练有素的免疫力-对COVID-19的影响

SARS-CoV-2感染可导致严重疾病，目前尚无特定疗法。使用羟氯喹预防或治疗SARS-CoV-2感染是有争议的，对其作用方式了解甚少。我们证明羟氯喹在功能和表观遗传水平上抑制训练的免疫，并伴随着细胞脂质组的深刻变化以及干扰素刺激基因的表达降低。训练有素的免疫力包括通过表观遗传重编程诱导的功能适应性，从而促进抗病毒先天免疫应答。因此，我们的发现表明，羟氯喹可能对SARS-CoV-2的抗病毒免疫反应没有有益作用。