Temporal association of reduced serum vitamin D with COVID-19 infection: A single-institution case-control and historical cohort study

Objectives: Vitamin D supplementation has been proposed for the prevention and treatment of COVID-19, but the relationship between the two is inconclusive: Reduced serum vitamin D may predispose to COVID-19, but it may also be a secondary consequence of infection. The objective of this study was to assess the temporal association between serum vitamin D levels and COVID-19. Design: A single-institution case-control study and a historical cohort study Setting: University of California San Diego (UCSD) Health System in San Diego, California Participants: Patients testing positive for COVID-19 from January 1, 2020 to September 30, 2020 with serum 25-hydroxy-vitamin D (25(OH)D) measured within 180 days of diagnosis. Patients were separated based on whether 25(OH)D was measured before (n=107; "pre-diagnosis") or after (n=203; "post-diagnosis") COVID-19 diagnosis. Subjects with 25(OH)D assessments prior to COVID-19 diagnosis were evaluated using a case-control study design, while subjects with 25(OH)D measured after COVID-19 diagnosis were analyzed with a historical cohort study design. Primary and Secondary Outcome Measures: In the pre-diagnosis study, a conditional logistic regression was performed using COVID-19 infection status as the binary dependent variable. In the post-diagnosis study, an ordinary least squares regression was performed using serum 25(OH)D levels as the continuous dependent variable. Results: Serum 25(OH)D levels were not associated with the odds of subsequently testing positive for COVID-19 (OR 1.00, 95% CI: 0.98 to 1.02, p = 0.982). However, COVID-19 positive individuals had serum 25(OH)D measurements that were lower by 2.70 ng/mL (95% CI: -5.19 to -0.20, p = 0.034) compared to controls. Conclusions: In our study population, serum 25(OH)D levels were not associated with risk of testing positive for COVID-19 but were reduced in subjects after being diagnosed with COVID-19 infection. These results raise the possibility that reduced serum 25(OH)D may be a consequence and not a cause of COVID-19 infection.