Vitamin D deficiency prolongs hospitalization in moderate-to-severe COVID-19

Patients with moderate-to-severe COVID-19 who have severe serum 25-hydroxyvitamin D (25[OH]D) deficiency (<10 ng/mL) tend to be hospitalized longer than those with higher 25(OH)D concentrations, a study in Brazil has shown. However, such association is not significant in multivariable analysis.

“Prospective studies should test whether correcting severe 25(OH)D deficiency could improve the prognosis of patients with COVID-19,” the researchers said.

Two hundred twenty patients with moderate-to-severe COVID-19 were recruited from two hospitals in Sao Paulo, Brazil. Serum 25(OH)D concentrations of participants were categorized as follows: <10 ng/mL, 10 to <20 ng/mL, 20 to <30 ng/mL, and ≥30 ng/mL, and <10 ng/mL and ≥10 ng/mL.

Hospital length of stay was the primary outcome, and the rate of patients needing invasive mechanical ventilation and mortality were the secondary outcomes.

No significant differences in the primary outcome were observed when comparing the four serum 25(OH)D categories (p=0.120). [Am J Clin Nutr 2021;114:598-604]

However, patients with 25(OH)D <10 ng/mL tended to have longer hospital length of stay (p=0.057) than those with 25(OH)D ≥10 ng/mL: 9.0 days, 95 percent confidence interval (CI), 6.4–11.6 vs 7.0 days, 95 percent CI, 6.6–7.4.

On the other hand, multivariable Cox proportional hazard models revealed no significant associations between 25(OH)D concentrations and the primary or secondary outcomes.

In earlier studies, lower 25(OH)D concentrations correlated with a worse prognosis in COVID-19 (ie, hospital length of stay, lung involvement, or mortality). [Osteoporos Int 2020;31:2495-2496; Eur J Nutr 2020;doi:10.1007/s00394-020-02411-0; J Nutr 2021;151:98-103]

Other studies did not find a significant link between serum 25(OH)D and clinical outcomes (ie, admission to the intensive care unit, requirements for mechanical ventilation, or mortality) in COVID-19 patients. [Nutr Hosp 2020;37:1039-1042; J Clin Endocrinol Metab 2020;doi:10.1210/clinem/dgaa733; Nutrients 2020;12:2775]

Such disagreement could be partially explained by the use of different cutoff values for defining 25(OH)D insufficiency and sufficiency.

“In the current study, the differences between the four 25(OH)D categories did not reach statistical significance for hospital length of stay, whereas severe 25(OH)D deficiency (<10 ng/mL) was associated with longer stays as compared with all other higher 25(OH)D concentrations,” the researchers said.

“Altogether, these findings appear to suggest that, at least for hospitalized patients with severe COVID-19, only severe 25(OH)D deficiency could be associated with a poor prognosis,” they added.

Vitamin D plays a significant role in the immune system by regulating both innate and adaptive immune response. [Eur J Endocrinol 2020;183:R133-147; Immunology 2011;134:123-139]

In addition, vitamin D contributes to antiviral responses in epithelial cells, producing antimicrobial peptides and inducing autophagy, as well as regulating inflammatory responses through the renin-angiotensin system, whose overactivation leads to poor prognosis in COVID-19. [Eur J Endocrinol 2020;183:R133-147; Aging Clin Exp Res 2020;32:2141-2158; Ir Med J 2020;113:81]

“This biological plausibility underlies the speculation that vitamin D sufficiency can elicit immunomodulatory and anti-inflammatory effects that could ultimately improve the recovery of COVID-19 patients,” the researchers said. [Lancet Diabetes Endocrinol 2020;8:570; Lancet Diabetes Endocrinol 2020;8:735-736]