Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults

In this cohort study of 18,148 individuals whose vitamin D levels were measured before the COVID-19 pandemic, low levels of vitamin D were associated with SARS-CoV-2 antibodies. However, after adjusting for age, sex, race/ethnicity, education, body mass index, blood pressure, smoking status, and geographical location, vitamin D level was not associated with SARS-CoV-2 antibody results.

• Of the 18,148 participants, 900 (5.0%) were SARS-CoV-2 seropositive, 10,876 (59.9%) had insufficient (<30 ng/mL) levels of vitamin D in the prepandemic period, and 4,498 (24.8%) had deficient (<20 ng/mL) levels of vitamin D in the prepandemic period.
• In multivariable models adjusting for age, sex, race/ethnicity, education, body mass index, blood pressure, smoking status, and geographical location, SARS-CoV-2 seropositivity was not associated with having a vitamin D level less than 20 ng/mL before (odds ratio [OR], 1.04; 95%CI, 0.88-1.22) or during (OR, 0.93; 95%CI, 0.79-1.09) the pandemic; it was also not associated with having a vitamin D level less than 30 ng/mL before (OR, 1.09; 95%CI, 0.93-1.27) or during (OR, 1.05; 95%CI, 0.91-1.23) the pandemic.

The 18,148 individuals (12,170 women, 67.1%; 5978 men, 32.9%) included in this study had test results for SARS-CoV-2 IgG in 2020 and vitamin D levels from the prepandemic (September 2019 to January 2020) and pandemic (August 2020 to November 2020) periods. The median age was 47 years (ranging 37-56 years).

• A limitation of this study is that the risk of SARS-CoV-2 seropositivity is not a perfect measurement of the risk of SARS-CoV-2 infection. Some seronegative individuals could have been infected with the SARS-CoV-2 virus but not identified by the serology assay used (the serology assay has a reported sensitivity of 90% to 100%). Newly infected individuals could have also been missed because they had not had enough time to develop IgG antibody, and infected individuals could have undergone seroreversion. However, sensitivity analysis suggests that SARS-CoV-2 seropositivity continued to not be associated with low levels of vitamin D after accounting for the loss of detecting seropositivity among some individuals who had COVID-19.
• Another limitation of this study is that because vitamin D status was not randomized, there might be residual confounders or unobserved variable bias.
• A further limitation was the potential selection bias due to the inclusion of only individuals who chose to participate in the screening and opted to be tested for SARS-CoV-2 antibodies; however, the characteristics of those who did not opt for serology testing appeared similar to those included in the study.

In this cohort study, SARS-CoV-2 seropositivity was not associated with low levels of vitamin D independently of other risk factors. These findings do not support the hypothesis that vitamin D plays a role in susceptibility to SARS-CoV-2 infection.

• This is a cohort study of employees and spouses who elected to be tested for SARS-CoV-2 IgG as part of an annual employer-sponsored health screening program conducted in August to November 2020. This program includes commonly assessed demographic, biometric, and laboratory variables, including total vitamin D measurement.
• Baseline (prepandemic) levels of vitamin D and potential confounders were obtained from screening results from the previous year (September 2019 to January 2020).Low total serum 25-hydroxyvitamin D, was defined as either <20 ng/mL (50 nmol/l) or <30 ng/mL (75 nmol/l), which represent threshold values for vitamin D deficiency and insufficiency, respectively.
• The main outcome was SARS-CoV-2 seropositivity, as determined with US Food and Drug Administration emergency use–authorized assays.
• The association of SARS-CoV-2 seropositivity with vitamin D levels was assessed by multivariable logistic regression analyses and propensity score analyses.

Li Y, Tong CH, Bare LA, Devlin JJ. Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults. JAMA Netw Open. 2021 May 3;4(5):e2111634. doi: 10.1001/jamanetworkopen.2021.11634. PMID: 34009346; PMCID: PMC8135000.