Cholecalciferol, calcifediol supplements boost protection against COVID-19

Supplementation with cholecalciferol or calcifediol to improve vitamin D status can lead to large, population-wide improvements in outcomes of the novel coronavirus disease (COVID-19), a recent study has found.

“Our results suggest that reaching a sufficient vitamin D status in patients supplemented with these vitamin D metabolites is associated with a reduced risk of SARS-CoV-2 infection and lower COVID-19 mortality,” the researchers said.

The study included adults living in Barcelona-Central Catalonia who had taken cholecalciferol or calcifediol supplementation between April 2019 to February 2020. Participants were propensity score-matched with untreated controls. Outcomes of interest were SARS-CoV-2 infection and COVID-19 severe illness and death.

After matching, the analysis for cholecalciferol included 108,343 treated participants and 216,686 untreated controls. In the respective arms, 4,352 and 9,142 patients were diagnosed with SARS-CoV-2 infection. Multivariate Cox regression analysis showed that cholecalciferol could mildly but significantly reduce the risk of COVID-19 (hazard ratio [HR], 0.95, 95 percent confidence interval [CI], 0.91–0.98; p=0.004). [J Endocrinol Invest 2021;doi:10.1007/s40618-021-01639-9]

On the other hand, cholecalciferol had no apparent impact on COVID-19 severity (HR, 0.97, 95 percent CI, 0.89–1.05; P=0.439) or mortality (HR, 0.96, 95 percent CI, 0.88–1.05; p=0.366).

However, looking at mean daily doses of cholecalciferol, expressed in 10-µg intervals, the researchers detected small but significant reductions in infection (HR, 0.97, 95 percent CI, 0.95–0.99; p=0.007), severity (HR, 0.92, 95 percent CI, 0.87–0.97; p=0.002), and mortality (HR, 0.90, 95 percent CI, 0.85–0.96; p=0.001).

Calcifediol analysis included 134,703 treated patients and 269,406 matched untreated controls. COVID-19 was diagnosed in 2,607 and 11,401 participants in the respective cohorts, suggesting that calcifediol supplementation had no significant impact on SARS-CoV-2 infection (HR, 0.99, 95 percent CI, 0.96–1.03; p=0.646).

Similarly, no significant differences in COVID-19 severity (HR, 1.00, 95 percent CI, 0.93–1.08; p=0.995) and mortality (HR, 1.01, 95 percent CI, 0.93–1.09; p=0.908) were detected between treated and untreated controls.

The findings suggest that vitamin D status affects COVID-19 outcome, as confirmed by multivariate analysis, which revealed an inverse correlation between serum levels of 25-hydroxyvitamin D and SARS-CoV-2 infection (HR, 0.97, 95 percent CI, 0.94–0.99; p=0.017).

Moreover, COVID-19 infection, severity, and mortality were all significantly lower in vitamin D-sufficient patients who were taking either cholecalciferol or calcifediol supplementation, as compared with their unsupplemented, vitamin D-deficient comparators.

“To the best of our knowledge, there are not published results describing the effects, at the population level, of cholecalciferol or calcifediol supplementation on COVID-19 outcomes,” the researchers said.

“In this large, population-based study, we observed that cholecalciferol or calcifediol supplementation seem to be beneficial against SARS-CoV-2 infection, COVID-19 severity, and COVID-19 mortality in patients,” they added.