During the COVID-19 pandemic, efforts have been made worldwide to develop effective therapies to address the devastating immune-mediated effects of SARS-CoV-2. With the exception of monoclonal antibody-mediated therapeutics and preventive approaches such as mass immunization, most experimental or repurposed drugs have failed in large randomized clinical trials (https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline). The worldwide spread of SARS-CoV-2 virus revealed specific susceptibilities to the virus among the elderly and individuals with age-related syndromes. These populations were more likely to experience a hyper-immune response characterized by a treatment-resistant acute lung pathology accompanied by multiple organ failure. These observations underscore the interplay between the virus, the biology of aging, and outcomes observed in the most severe cases of SARS-CoV-2 infection. The ectoenzyme CD38 has been implicated in the process of 'inflammaging' in aged tissues (1). In a current publication, Horenstein et al. present evidence to support the hypothesis that the CD38 plays a central role in altered immunometabolism resulting from COVID-19 infection. The authors discuss a critical but under-appreciated trifecta of CD38-mediated NAD⁺ metabolism, aging, and COVID-19 immune response and speculate that the CD38/NAD⁺ axis is a promising therapeutic target for this disease (2).

中文翻译：

---

NADase CD38 在 COVID 病理生理学中的意义

在 COVID-19 大流行期间，全世界都在努力开发有效的疗法，以解决 SARS-CoV-2 的破坏性免疫介导效应。除了单克隆抗体介导的治疗和预防方法（如大规模免疫）外，大多数实验性或重新利用的药物在大型随机临床试验中都失败了（https://www.who.int/publications/i/item/therapeutics-and- covid-19-生活指南）。SARS-CoV-2 病毒的全球传播揭示了老年人和患有年龄相关综合征的个体对该病毒的特定易感性。这些人群更有可能经历一种超免疫反应，其特征是伴有多器官衰竭的难治性急性肺病理学。这些观察结果强调了病毒、衰老生物学、以及在最严重的 SARS-CoV-2 感染病例中观察到的结果。胞外酶 CD38 与衰老组织中的“炎症”过程有关 (1)。在当前的出版物中，Horenstein 等人。目前的证据支持 CD38 在 COVID-19 感染导致的免疫代谢改变中起核心作用的假设。作者讨论了 CD38 介导的 NAD 的一个关键但未被充分认识的三重奏⁺代谢、衰老和 COVID-19 免疫反应，并推测 CD38/NAD ⁺轴是该疾病的有希望的治疗靶点 (2)。