The ongoing pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a disproportionate number of severe cases and deaths in older adults. Severe SARS-CoV-2-associated disease (coronavirus disease 2019 (COVID-19)) was declared a pandemic by the World Health Organization in March 2020 and is characterized by cytokine storm, acute respiratory distress syndrome, and in some cases by systemic inflammation–related pathology. Currently, our knowledge of the determinants of severe COVID-19 is primarily observational. Here, I review emerging evidence to argue that monocytes, a circulating innate immune cell, are principal players in cytokine storm and associated pathologies in COVID-19. I also describe changes in monocyte function and phenotype that are characteristic of both aging and severe COVID-19, which suggests a potential mechanism underlying increased morbidity and mortality due to SARS-CoV-2 infection in older adults. The innate immune system is therefore a potentially important target for therapeutic treatment of COVID-19, but experimental studies are needed, and SARS-CoV-2 presents unique challenges for pre-clinical and mechanistic studies in vivo. The immediate establishment of colonies of SARS-CoV-2-susceptible animal models for aging studies, as well as strong collaborative efforts in the geroscience community, will be required in order to develop the therapies needed to combat severe COVID-19 in older adult populations.

中文翻译：

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严重的 COVID-19 和衰老：单核细胞是关键吗？

持续流行的严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 导致老年人出现大量重症病例和死亡。世界卫生组织于 2020 年 3 月宣布严重 SARS-CoV-2 相关疾病（2019 年冠状病毒病 (COVID-19)）为大流行病，其特点是细胞因子风暴、急性呼吸窘迫综合征，在某些情况下还表现为全身炎症–相关病理学。目前，我们对严重 COVID-19 决定因素的了解主要是观察性的。在这里，我回顾了新出现的证据，认为单核细胞（一种循环的先天免疫细胞）是细胞因子风暴和 COVID-19 相关病理的主要参与者。我还描述了单核细胞功能和表型的变化，这是衰老和严重 COVID-19 的特征，这表明老年人中 SARS-CoV-2 感染导致发病率和死亡率增加的潜在机制。因此，先天免疫系统是治疗 COVID-19 的潜在重要目标，但需要进行实验研究，并且 SARS-CoV-2 给临床前和体内机制研究带来了独特的挑战。为了开发在老年人群中对抗严重的 COVID-19 所需的疗法，需要立即建立用于衰老研究的 SARS-CoV-2 易感动物模型群体，以及老年科学界的强有力的合作努力。