We read with great interest the review article by Matricardi and colleagues1 depicting mechanisms of disease for COVID‐19 and analyzing both viral and host factors influencing its course. We particularly agree with authors on the pivotal role of innate immunity in the very early phase of disease, being crucial for the subsequent evolution. Most known weapons of innate immune system are represented by natural antibodies, non‐specific antimicrobial proteins, interferons, cytokines, and cellular elements (ie, natural killer cells).1 However, innate immunity could be influenced by other, still underrecognized, factors.

At present, a solid proof of evidence is available on the ability of vitamin D in modulating immune response.2 Most of the data are available from the field of bacterial infections and sepsis,3 being low vitamin D levels associated with a higher risk of infection and mortality.4

In addition, vitamin D could play a role against viruses by maintaining physical barriers (ie, tight junctions and gap junction), enhancing natural immunity (ie, production of cathelicidin and defensins), and modulating adaptive immune response (ie, modulation of TH1/TH2 response and inflammation).5 On this connection, emerging data support the role of vitamin D supplementation in reducing the risk and severity of influenza.5 Both influenza and COVID‐19 show their maximum spread in winter season and the highest severity in elderly people. Reduced vitamin D levels could represent a possible pathophysiological explanation, among others, in both cases.5, 6 With this regard, it has been hypothesized that variations in vitamin D status across countries and latitudes could, at least in part, explain variations of mortality from COVID‐19.6, 7

However, at present the exact vitamin D status among COVID‐19 patients is unknown.7 Moreover, the role and mechanisms of vitamin D in the treatment of COVID‐19 are still unexplored and several interventional trials are ongoing. Should these hypotheses be confirmed, universal vitamin D supplementation would represent a possible and inexpensive strategy to enhance natural immunity against COVID‐19.

我们饶有兴趣地阅读了 Matricardi 及其同事1撰写的综述文章，该文章描述了 COVID-19 的疾病机制，并分析了影响其病程的病毒和宿主因素。我们特别同意作者的观点，即先天免疫在疾病的早期阶段发挥着关键作用，对随后的进化至关重要。最已知的先天免疫系统武器以天然抗体、非特异性抗菌蛋白、干扰素、细胞因子和细胞因子（即自然杀伤细胞）为代表。 1然而，先天免疫可能会受到其他尚未得到充分认识的因素的影响。

目前，维生素 D 调节免疫反应的能力已有确凿的证据。 2大多数数据来自细菌感染和败血症领域， 3维生素 D 水平低与感染和死亡风险较高相关。 4

此外，维生素D还可以通过维持物理屏障（即紧密连接和间隙连接）、增强自然免疫（即产生抗菌素和防御素）以及调节适应性免疫反应（即调节TH1/ TH2 反应和炎症）。 5在这方面，新出现的数据支持补充维生素 D 在降低流感风险和严重程度方面的作用。 5流感和 COVID-19 均在冬季传播最严重，在老年人中最严重。在这两种情况下，维生素 D 水平降低可能是一种可能的病理生理学解释。 5, 6在这方面，有人假设不同国家和纬度之间维生素 D 状况的差异可以至少部分解释 COVID-19 死亡率的差异。 6, 7

然而，目前 COVID-19 患者中确切的维生素 D 状况尚不清楚。 7此外，维生素 D 在治疗 COVID-19 中的作用和机制仍有待探索，多项干预试验正在进行中。如果这些假设得到证实，普遍补充维生素 D 将成为增强针对 COVID-19 的自然免疫力的一种可能且廉价的策略。