Karonova Tatiana L, Kudryavtsev Igor V, Golovatyuk Ksenia A, Aquino Arthur D, Kalinina Olga V, Chernikova Alena T, Zaikova Ekaterina K, Lebedev Denis A, Bykova Ekaterina S, Golovkin Alexey S, Shlyakhto Evgeny V
Almazov National Medical Research Centre, 197341 Saint-Petersburg, Russia.
Institute of Experimental Medicine, 197376 Saint-Petersburg, Russia.
Pharmaceuticals (Basel). 2022 Mar 2;15(3):305. doi: 10.3390/ph15030305.
A low 25-hydroxyvitamin D (25(OH)D) level is considered as an independent risk factor for COVID-19 severity. However, the association between vitamin D status and outcomes in COVID-19 is controversial. In the present study we investigate the association between the serum 25(OH)D level, immune response, and clinical disease course in patients with COVID-19. A total of 311 patients hospitalized with COVID-19 were enrolled. For patients with a vitamin D deficiency/insufficiency, the prevalence of severe COVID-19 was higher than in those with a normal 25(OH)D level (p < 0.001). The threshold of 25(OH)D level associated with mortality was 11.4 ng/mL (p = 0.003, ROC analysis). The frequency of CD3+CD4+ T helper (Th) cells was decreased in patients with 25(OH)D level ≤ 11.4 ng/mL, compared to healthy controls (HCs). There were no differences in the frequency of naive, central memory (CM), effector memory (EM), and terminally differentiated effector memory Th cells in patients with COVID-19 compared to HCs. The frequency of T-follicular helpers was decreased both in patients with 25(OH)D level > 11.4 ng/mL (p < 0.001) and 25(OH)D level ≤ 11.4 ng/mL (p = 0.003) compared to HCs. Patients with 25(OH)D level > 11.4 ng/mL had an increased frequency of Th2 CM (p = 0.010) and decreased Th17 CM (p < 0.001). While the frequency of Th2 EM was significantly increased, the frequency of Th17 EM was significantly decreased in both groups compared to HCs. Thus, 25(OH)D level is an independent risk factor for the disease severity and mortality in patients with COVID-19. We demonstrate that the serum 25(OH)D level ≤ 11.4 ng/mL is associated with the stimulation of Th2 and the downregulation of Th17 cell polarization of the adaptive immunity in patients with COVID-19.
低水平的25-羟基维生素D（25(OH)D）被认为是新冠病毒疾病严重程度的独立危险因素。然而，维生素D状态与新冠病毒疾病预后之间的关联存在争议。在本研究中，我们调查了新冠病毒疾病患者血清25(OH)D水平、免疫反应和临床病程之间的关联。共纳入311例因新冠病毒疾病住院的患者。维生素D缺乏/不足的患者中，重症新冠病毒疾病的患病率高于25(OH)D水平正常的患者（p<0.001）。与死亡率相关的25(OH)D水平阈值为11.4 ng/mL（p=0.003，ROC分析）。与健康对照（HCs）相比，25(OH)D水平≤11.4 ng/mL的患者中CD3+CD4+辅助性T（Th）细胞频率降低。与HCs相比，新冠病毒疾病患者中初始、中央记忆（CM）、效应记忆（EM）和终末分化效应记忆Th细胞的频率没有差异。与HCs相比，25(OH)D水平>11.4 ng/mL（p<0.001）和25(OH)D水平≤11.4 ng/mL（p=0.003）的患者中T滤泡辅助细胞频率均降低。25(OH)D水平>11.4 ng/mL的患者中Th2 CM频率增加（p=0.010），Th17 CM频率降低（p<0.001）。与HCs相比，两组中Th2 EM频率均显著增加，Th17 EM频率均显著降低。因此，25(OH)D水平是新冠病毒疾病患者疾病严重程度和死亡率的独立危险因素。我们证明，血清25(OH)D水平≤11.4 ng/mL与新冠病毒疾病患者适应性免疫中Th2的激活和Th17细胞极化的下调有关。
