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近日，美国耶鲁大学医学院Akiko Iwasaki及其研究团队发现导致不同COVID-19疾病结局的性别差异原因。这一研究成果于2020年8月26日在线发表在国际学术期刊《自然》上。

研究人员检查了COVID-19患者的病毒载量、SARS-CoV-2特异性抗体滴度、血浆细胞因子以及血细胞表型的性别差异。通过将分析集中于未接受免疫调节药物的中度疾病患者，研究结果表明，男性患者血浆中天然免疫细胞因子（如IL-8和IL-18）的血浆水平更高，并且非经典单核细胞的诱导作用更强。

相比之下，SARS-CoV-2感染期间女性患者的T细胞活化能力明显强于男性患者，而后者在老年患者中持续存在。重要的是，研究人员发现不良的T细胞反应与患者的年龄呈负相关，并且与男性患者（而非女性患者）的病情恶化相关。相反，女性患者较高的先天免疫细胞因子与疾病恶化相关，而男性患者则不然。这些发现揭示了在COVID-19中性别差异的可能原因，并为开发基于性别的COVID-19治疗方法提供了重要基础。

据了解，越来越多的证据表明，COVID-19的临床结果存在性别差异。然而，目前尚不清楚性别之间对SARS-CoV-2的免疫反应是否不同，以及这种差异是否解释了男性对COVID-19的易感性。

附：英文原文

Title: Sex differences in immune responses that underlie COVID-19 disease outcomes

Author: Takehiro Takahashi, Mallory K. Ellingson, Patrick Wong, Benjamin Israelow, Carolina Lucas, Jon Klein, Julio Silva, Tianyang Mao, Ji Eun Oh, Maria Tokuyama, Peiwen Lu, Arvind Venkataraman, Annsea Park, Feimei Liu, Amit Meir, Jonathan Sun, Eric Y. Wang, Arnau Casanovas-Massana, Anne L. Wyllie, Chantal B.F. Vogels, Rebecca Earnest, Sarah Lapidus, Isabel M. Ott, Adam J. Moore, Albert Shaw, John B. Fournier, Camila D. Odio, Shelli Farhadian, Charles Dela Cruz, Nathan D. Grubaugh, Wade L. Schulz, Aaron M. Ring, Albert I. Ko, Saad B. Omer, Akiko Iwasaki

Issue&Volume: 2020-08-26

Abstract: A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)1–5. However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. By focusing our analysis on patients with moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age. Importantly, we found that a poor T cell response negatively correlated with patients’ age and was associated with worse disease outcome in male patients, but not in female patients. Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients. These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of men and women with COVID-19.

DOI: 10.1038/s41586-020-2700-3

Source: https://www.nature.com/articles/s41586-020-2700-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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