Wray Susan, Arrowsmith Sarah
Department of Women's and Children's Health, University of Liverpool, Liverpool, United Kingdom.
Front Physiol. 2021 Feb 9;12:627260. doi: 10.3389/fphys.2021.627260. eCollection 2021.
The scale of the SARS-CoV-2 pandemic has thrust a spotlight on the sex-based differences in response to viral diseases; morbidity and mortality are greater in men than women. We outline the mechanisms by which being female offers a degree of protection from COVID19, that persists even when confounders such as comorbidities are considered. The physiological and immunological mechanisms are fascinating and range from incomplete X chromosome inactivation of immune genes, a crucial role for angiotensin converting enzyme 2 (ACE2), and regulation of both immune activity and ACE2 by sex steroids. From this flows understanding of why lung and other organs are more susceptible to COVID19 damage in men, and how their distinct immunological landscapes need to be acknowledged to guide prognosis and treatment. Pregnancy, menopause, and hormone replacement therapy bring changed hormonal environments and the need for better stratification in COVID19 studies. We end by noting clinical trials based on increasing estrogens or progesterone or anti-testosterone drugs; excellent examples of translational physiology.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）大流行的规模使人们聚焦于应对病毒性疾病时基于性别的差异；男性的发病率和死亡率高于女性。我们概述了女性对2019冠状病毒病（COVID-19）具有一定程度保护作用的机制，即使在考虑合并症等混杂因素时这种保护作用依然存在。生理和免疫机制十分引人关注，包括免疫基因X染色体不完全失活、血管紧张素转换酶2（ACE2）的关键作用，以及性类固醇对免疫活性和ACE2的调节。由此可以理解为何男性的肺和其他器官更容易受到COVID-19的损害，以及如何认识他们独特的免疫格局以指导预后和治疗。怀孕、更年期和激素替代疗法带来了激素环境的变化，以及在COVID-19研究中进行更好分层的需求。我们最后提到了基于增加雌激素或孕激素或抗雄激素药物的临床试验；这些都是转化生理学的优秀范例。
