Calcifediol treatment and COVID-19-related outcomes
X Nogues, D Ovejero, J M Quesada-Gomez, R Bouillon, D Arenas, J Pascual, J Villar-Garcia, A Rial, C Gimenez-Argente, M L Cos, J Rodriguez-Morera, I Campodarve, R Guerri-Fernandez, M Pineda-Moncusí, PhD Natalia Garcia-Giralt
Background COVID-19 is a major health problem because of acute respiratory distress syndrome, saturation of intensive care units (ICU) and mortality.
Methods Our study aims to elucidate the effect of calcifediol [25(OH)D 3 ] treatment on ICU admission and mortality, in patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 participants were included. Participants (n=551) were randomly assigned to calcifediol treatment (532 ug on day one and 266 ug on day 3, 7, 15, and 30) at the time of hospital admission or as controls (n=379). Findings ICU assistance was required by 110 (11.8%) participants. Out of 551 patients treated with calcifediol at admission, 30 (5.4%) required ICU, compared to 80 out of 379 controls (21.1%; p<0.0001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, gender, linearized 25(OH)D levels at baseline, and comorbidities showed that treated patients had a reduced risk to require ICU (RR 0.18 [95% CI 0.11;0.29]). Baseline 25(OH)D levels inversely correlated with the risk of ICU admission (RR 0.53 [95% CI 0.35;0.80]). Overall mortality was 10%. In the Intention-to-treat analysis, 36 (6.5%) out of 551 patients treated with calcifediol at admission died compared to 57 patients (15%) out of 379 controls (p=0.001). Adjusted results showed a reduced mortality for more of 60%. Higher baseline 25(OH)D levels were significantly associated with decreased mortality (RR 0.40 [95% CI 0.24;0.67]). Age and obesity were also predictors of mortality.
Interpretation In patients hospitalized with COVID-19, calcifediol treatment at the time of hospitalization significantly reduced ICU admission and mortality.
Implications of all the available evidence Vitamin D deficiency is common and even more so in COVID-19 patients compared to the general population. Rapid correction of such deficiency by calcifediol is easy, cheap, and appears as highly effective to control disease severity and avoid fatal outcomes in the setting of SARS-CoV-2 infection.
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DOI record:
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"DOI": "10.1210/clinem/dgab405",
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Context</jats:title>\n <jats:p>COVID-19 is a major health problem because of saturation of intensive care units (ICU) and mortality. Vitamin D has emerged as a potential treatment able to reduce the disease severity.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Objective</jats:title>\n <jats:p>This work aims to elucidate the effect of 25(OH)D3 (calcifediol) treatment on COVID-19–related outcomes.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>This observational cohort study was conducted from March to May 2020, among patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 patients with COVID-19 were included; 92 were excluded because of previous calcifediol intake. Of the remaining 838, a total of 447 received calcifediol (532 μg on day 1 plus 266 μg on days 3, 7, 15, and 30), whereas 391 were not treated at the time of hospital admission (intention-to-treat). Of the latter, 53 patients were treated later during ICU admission and were allocated in the treated group in a second analysis. In healthy individuals, calcifediol is about 3.2-fold more potent on a weight basis than cholecalciferol. Main outcome measures were ICU admission and mortality.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>ICU assistance was required by 102 (12.2%) participants. Out of 447 patients treated with calcifediol at admission, 20 (4.5%) required the ICU, compared to 82 (21%) out of 391 nontreated (P &lt; .001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, sex, linearized 25-hydroxyvitamin D levels at baseline, and comorbidities showed that treated patients had a reduced risk of requiring the ICU (odds ratio [OR] 0.13; 95% CI 0.07-0.23). Overall mortality was 10%. In the intention-to-treat analysis, 21 (4.7%) out of 447 patients treated with calcifediol at admission died compared to 62 patients (15.9%) out of 391 nontreated (P = .001). Adjusted results showed a reduced mortality risk with an OR of 0.21 (95% CI, 0.10-0.43). In the second analysis, the obtained OR was 0.52 (95% CI, 0.27-0.99).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>In patients hospitalized with COVID-19, calcifediol treatment significantly reduced ICU admission and mortality.</jats:p>\n </jats:sec>",
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