Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
Program in Immunology, University of Michigan, Ann Arbor, MI 48109; and.
J Immunol. 2020 Jul 15;205(2):313-320. doi: 10.4049/jimmunol.2000380. Epub 2020 Jun 3.
Aging impairs immunity to promote diseases, especially respiratory viral infections. The current COVID-19 pandemic, resulting from SARS-CoV-2, induces acute pneumonia, a phenotype that is alarmingly increased with aging. In this article, we review findings of how aging alters immunity to respiratory viral infections to identify age-impacted pathways common to several viral pathogens, permitting us to speculate about potential mechanisms of age-enhanced mortality to COVID-19. Aging generally leads to exaggerated innate immunity, particularly in the form of elevated neutrophil accumulation across murine and large animal studies of influenza infection. COVID-19 patients who succumb exhibit a 2-fold increase in neutrophilia, suggesting that exaggerated innate immunity contributes to age-enhanced mortality to SARS-CoV-2 infection. Further investigation in relevant experimental models will elucidate the mechanisms by which aging impacts respiratory viral infections, including SARS-CoV-2. Such investigation could identify therapies to reduce the suffering of the population at large, but especially among older people, infected with respiratory viruses.
衰老大幅削弱免疫功能，进而导致各种疾病，尤其是呼吸道病毒感染。目前由 SARS-CoV-2 引发的 COVID-19 大流行会导致急性肺炎，且该疾病在老年人中的发病率显著上升。本文通过综述衰老如何改变机体对呼吸道病毒感染的免疫反应，确定了几种病毒病原体共有的受年龄影响的途径，进而推测出 COVID-19 导致老年人死亡率升高的潜在机制。衰老通常会导致固有免疫反应过度，尤其是在流感感染的啮齿类动物和大型动物研究中，表现为中性粒细胞积累增加。死于 COVID-19 的患者中性粒细胞增多增加了两倍，这表明固有免疫反应过度可能导致 SARS-CoV-2 感染的死亡率增加。在相关实验模型中进一步研究，将阐明衰老影响呼吸道病毒感染（包括 SARS-CoV-2）的机制。此类研究可以确定相关疗法，减轻受呼吸道病毒感染的人群，尤其是老年人的痛苦。
