Objective

The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.

Design

Parallel pilot randomized open label, double-masked clinical trial.

Setting

University hospital setting (Reina Sofia University Hospital, Córdoba Spain.)

Participants

76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1).

Procedures

All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths.

Results

Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X² Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.

Conclusion

Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

中文翻译：

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“骨化二醇治疗和最佳可用疗法与最佳可用疗法对因 COVID-19 住院的重症监护病房入院率和死亡率的影响：一项初步随机临床研究”。

客观的

维生素 D 内分泌系统可能对参与 COVID-19 进展的细胞和组织产生多种作用，尤其是通过减少急性呼吸窘迫综合征。骨化二醇可迅速增加血清 25OHD 浓度。因此，我们评估了骨化二醇治疗对因 COVID-19 住院的西班牙患者重症监护室入院率和死亡率的影响。

设计

平行试点随机开放标签、双盲临床试验。

环境

大学医院环境（Reina Sofia University Hospital, Córdoba Spain.）

参加者

连续 76 名因 COVID-19 感染住院的患者，有急性呼吸道感染的临床表现，通过病毒性肺炎的影像学表现和 SARS-CoV-2 PCR 阳性，严重程度为 CURB65（如果总分 > 1，建议住院） ).

程序

所有住院患者都接受了相同标准护理（根据医院方案）的最佳可用疗法，包括羟氯喹（第一天每 12 小时 400 毫克，接下来 5 天每 12 小时 200 毫克）、阿奇霉素（ 500 mg 口服，持续 5 天。符合条件的患者在入院当天通过电子随机化以 2 骨化二醇：1 无骨化二醇的比例分配口服骨化二醇（0.532 mg）或不服用。骨化二醇治疗组的患者继续口服骨化二醇(0.266 mg) 第 3 天和第 7 天，然后每周一次，直到出院或入住 ICU。有效性结果包括 ICU 入住率和死亡率。

结果

在接受骨化二醇治疗的 50 名患者中，一名需要入住 ICU (2%)，而在 26 名未接受治疗的患者中，有 13 名 (50%) 需要入住 (50%) p 值 X ² Fischer 检验 p < 0.001。ICU 接受骨化二醇治疗与未接受骨化二醇治疗的患者的单变量风险估计比值比：0.02（95%CI 0.002-0.17）。接受骨化二醇治疗与未接受骨化二醇治疗的 ICU 患者的多变量风险估计比值比（根据高血压和 T2DM 调整）：0.03（95%CI：0.003-0.25）。在接受骨化二醇治疗的患者中，没有一人死亡，并且全部出院，没有出现并发症。未入住 ICU 的 13 名未接受骨化二醇治疗的患者已出院。入住重症监护病房的 13 名患者中，有 2 人死亡，其余 11 人出院。

结论

我们的初步研究表明，给予高剂量骨化二醇或维生素 D 内分泌系统的主要代谢物 25-羟基维生素 D，可显着减少因 COVID-19 而需要住院治疗的患者对 ICU 治疗的需求。骨化二醇似乎能够减轻疾病的严重程度，但需要对适当匹配的组进行更大规模的试验才能得出明确的答案。