Division of Infectious Disease, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
Division of Nephrology, Department of Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan.
Int J Mol Sci. 2021 May 16;22(10):5251. doi: 10.3390/ijms22105251.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and β-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4 T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4 T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin-angiotensin-aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill's causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.
新型冠状病毒病（COVID-19）是由严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）引起的，目前仍是一场持续的全球卫生危机。SARS-CoV-2 病毒颗粒被吸入后，立即被肺泡 II 型上皮细胞捕获并引发局部固有免疫。这些颗粒可以感染循环中的巨噬细胞，然后将冠状病毒抗原呈递给 T 细胞。随后，各种类型的 T 细胞被激活和分化，以及不可控的细胞因子释放（也称为细胞因子风暴），导致组织破坏和免疫反应放大。维生素 D 通过激活 Toll 样受体 2 增强了对抗 COVID-19 所需的固有免疫。它还通过促进 cathelicidin 和 β-防御素的表达和分泌来增强抗菌肽的合成；通过形成自噬体来促进自噬；并增加巨噬细胞内溶酶体降解酶的合成。关于适应性免疫，维生素 D 通过激活 T 细胞依赖性 B 细胞来增强 CD4 T 细胞，抑制辅助性 T 细胞 17 细胞，并促进病毒特异性抗体的产生。此外，维生素 D 通过核因子 kappa B 信号通路抑制 CD4 T 细胞释放促炎细胞因子，从而抑制细胞因子风暴的发展。SARS-CoV-2 进入细胞后，其刺突蛋白与血管紧张素转换酶 2（ACE2）受体结合。维生素 D 增加 ACE2 的生物利用度和表达，这可能负责捕获和失活病毒。肾素-血管紧张素-醛固酮系统（RAS）的激活负责与 SARS-CoV-2 相关的组织破坏、炎症和器官衰竭。维生素 D 抑制肾素的表达，是 RAS 的负调节剂。总之，维生素 D 通过固有免疫和适应性免疫的激活、ACE2 表达和 RAS 系统的抑制之间的相互作用，通过一种新的复杂机制来保护身体免受 SARS-CoV-2 的侵害。多项观察性研究表明，血清 25 羟维生素 D 浓度与 COVID-19 的发病率或严重程度呈负相关。迄今为止收集到的证据在生物系统中通常符合希尔因果关系标准，尽管实验验证不足。我们推测，充足的维生素 D 补充可能对减轻 COVID-19 的进展和严重程度至关重要。需要进一步的研究来确定 COVID-19 不同人群的维生素 D 补充剂量和效果。
