Correlation between 25-hydroxyvitamin D/D3 Deficiency and COVID-19 Disease Severity in Adults from Northern Colorado

Abstract

Vitamin D deficiency is common in the United States and leads to altered immune function, including T cell and macrophage activity that may impact responses to SARS-CoV-2 infection. This study investigated 131 adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR and 18 adults with no COVID-19 diagnosis that were recruited from the community or hospital into the Northern Colorado Coronavirus Biorepository (NoCo-COBIO). Participants consented to enrollment for a period of 6 months and provided biospecimens at multiple visits for longitudinal analysis. Plasma 25-hydroxyvitamin D levels were quantified by LC-MS/MS at the initial visit (n = 149) and after 4 months (n = 89). Adults were classified as deficient (<30 nM or <12 ng/mL), insufficient (<30−50 nM or 12−20 ng/mL), or optimal (50−75 nM or >20 ng/mL) for 25-hydroxyvitamin D status. Fisher’s exact test demonstrated an association between disease severity, gender, and body mass index (BMI) at baseline. Mixed model analyses with Tukey-Kramer were used for longitudinal analysis according to BMI. Sixty-nine percent (n = 103) of the entire cohort had optimal levels of total 25(OH)D, 22% (n = 32) had insufficient levels, and 9% (n = 14) had deficent levels. Participants with severe disease (n = 37) had significantly lower 25-hydroxyvitamin D (total 25(OH)D) when compared to adults with mild disease (p = 0.006) or no COVID-19 diagnosis (p = 0.007). There was 44% of the cohort with post-acute sequalae of COVID-19 (PASC) as defined by experiencing at least one of the following symptoms after 60 days’ post-infection: fatigue, dyspnea, joint pain, chest pain, forgetfulness or absent-mindedness, confusion, or difficulty breathing. While significant differences were detected in 25-hydroxyvitamin D status by sex and BMI, there were no correlations between 25-hydroxyvitamin D for those without and without PASC. This longitudinal study of COVID-19 survivors demonstrates an important association between sex, BMI, and disease severity for 25-hydroxyvitamin D deficiency during acute stages of infection, yet it is not clear whether supplementation efforts would influence long term outcomes such as developing PASC.

Keywords: 25-hydroxyvitamin D; COVID-19; Vitamin D; cholecalciferol D3; deficiency; ergocalciferol D2.

Figure 1

Study design for plasma total 25(OH)D and D3 analysis from 131 adults diagnosed with COVID-19 and 18 adults with no COVID-19 diagnosis. The plasma total 25(OH)D and D3 concentrations were analyzed for statistical comparison between adults with and without COVID-19 and for comparison from time of enrollment and after 4 months.

Figure 2

Plasma total 25(OH)D status was significantly different between participants with severe disease and those adults without COVID-19. Above the red horizontal line indicates optimal level, between the blue and red horizontal lines indicates sufficient, and below the blue horizontal lines indicates deficient. White circles indicate no co-morbidities/pre-existing chronic disease conditions, and grey circles indicate one or more co-morbidities/pre-existing chronic disease condition(s). Results were analyzed using SAS 9.4 (Cary, NC, USA). The * indicates significant total 25(OH)D p-value < 0.05.

Figure 3

Longitudinal plasma levels of total 25(OH)D for adults diagnosed with COVID-19 at time of enrollment and after 4 months. (A) Plasma total 25(OH)D was compared across mild, moderate, and severe COVID-19 disease at time of enrollment; orange circles indicate PASC at month 4. (B) Plasma total 25(OH)D for adults enrolled in the acute phase (days 1–14 post PCR+) and at month 4 (day 83–140 post PCR+); Left panel represents participants trending to have an increase in total 25(OH)D from day 1–14 to day 83–140; Right panel shows trending reductions in total 25(OH)D from day 1–14 to day 83–140. For days 83–140, the white circles indicate no PASC, orange circles indicate PASC; below blue line indicates deficient, between blue and red line indicates insufficient, and above red line indicates optimal total 25(OH)D. No statistical significance was detected between the PASC groups or timepoints.