Correlation between 25-hydroxyvitamin D/D3 Deficiency and COVID-19 Disease Severity in Adults from Northern Colorado
Bridget A Baxter, Michaela G Ryan, Stephanie M Lavergne, Sophia Stromberg, Kailey Berry, Madison Tipton, Nicole Natter, Nikiah Nudell, Kim Mcfann, Julie Dunn, Tracy L Webb, Michael Armstrong, Nichole Reisdorph, Elizabeth P Ryan
Nutrients, doi:10.3390/nu14245204
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.
Conflicts of Interest: The authors declare no conflict of interest.
References
Aloia, Patel, Dimaano, Li-Ng, Talwar et al., Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration, Am. J. Clin. Nutr,
doi:10.1093/ajcn/87.6.1952Alquaiz, Kazi, Fouda, Alyousefi, Age and gender differences in the prevalence and correlates of vitamin D deficiency, Arch. Osteoporos,
doi:10.1007/s11657-018-0461-5Baz-Hecht, Goldfine, The impact of vitamin D deficiency on diabetes and cardiovascular risk, Curr. Opin. Endocrinol. Diabetes Obes,
doi:10.1097/MED.0b013e3283372859Biesalski, Vitamin D deficiency and co-morbidities in COVID-19 patients-A fatal relationship?, Nfs J
Bishop, Ismailova, Dimeloe, Hewison, White, Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory, JBMR Plus,
doi:10.1002/jbm4.10405Braun, Gibbons, Litonjua, Giovannucci, Christopher, Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality, Crit. Care Med,
doi:10.1097/CCM.0b013e31822d74f3Chen, Zhang, Ge, Du, Deb et al., Vitamin D receptor inhibits nuclear factor κB activation by interacting with IκB kinase β protein, J. Biol. Chem,
doi:10.1074/jbc.M113.467670Connors, Sheikholislam, Irias, Vitamin D toxicity after dieting in hypoparathyroidism, Pediatrics
Edward, Macdonald, Zeisel, Present Knowledge in Nutrition
Forrest, Stuhldreher, Prevalence and correlates of vitamin D deficiency in US adults, Nutr. Res
Hars, Mendes, Serratrice, Herrmann, Gold et al., Sex-specific association between vitamin D deficiency and COVID-19 mortality in older patients, Osteoporos. Int,
doi:10.1007/s00198-020-05677-6Hayashi, Okamatsu, Ogasawara, Tsugawa, Isoda et al., Oral Supplementation of the Vitamin D Metabolite 25(OH)D3 Against Influenza Virus Infection in Mice, Nutrients,
doi:10.3390/nu12072000Khan, Ullah, Randhawa, Iqtadar, Butt et al., Role of Vitamin D in reducing number of acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) patients, Pak. J. Med. Sci,
doi:10.12669/pjms.333.12397Laires, Nunes, Population-based Estimates for High Risk of Severe COVID-19 Disease due to Age and Underlying Health Conditions, Acta Med. Port,
doi:10.20344/amp.14222Latic, Erben, Vitamin, Cardiovascular Disease, with Emphasis on Hypertension, Atherosclerosis, and Heart Failure, Int. J. Mol. Sci,
doi:10.3390/ijms21186483Lavergne, Stromberg, Baxter, Webb, Dutt et al., A longitudinal SARS-CoV-2 biorepository for COVID-19 survivors with and without post-acute sequelae, BMC Infect. Dis,
doi:10.1186/s12879-021-06359-2Lima, Rocha, Moreira, Genetic and epigenetic control of ACE2 expression and its possible role in COVID-19, Cell Biochem. Funct,
doi:10.1002/cbf.3648Lips, Cashman, Lamberg-Allardt, Bischoff-Ferrari, Obermayer-Pietsch et al., Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: A position statement of the European Calcified Tissue Society, Eur. J. Endocrinol,
doi:10.1530/EJE-18-0736Looker, Schleicher, Vitamin, Status: United States, 2001-2006, NCHS Data Brief
Lucas, Wong, Klein, Castro, Silva et al., Longitudinal analyses reveal immunological misfiring in severe COVID-19, Nature,
doi:10.1038/s41586-020-2588-yMcfann, Baxter, Lavergne, Stromberg, Berry et al., Quality of Life (QoL) Is Reduced in Those with Severe COVID-19 Disease, Post-Acute Sequelae of COVID-19, and Hospitalization in United States Adults from Northern Colorado, Int. J. Environ. Res. Public Health,
doi:10.3390/ijerph182111048Mcmullan, Borgi, Curhan, Fisher, Forman, The effect of vitamin D on renin-angiotensin system activation and blood pressure: A randomized control trial, J. Hypertens,
doi:10.1097/HJH.0000000000001220Molloy, Murphy, Vitamin, COVID-19 and Children, Ir. Med. J
Murdoch, Slow, Chambers, Jennings, Stewart et al., Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: The VIDARIS randomized controlled trial, JAMA,
doi:10.1001/jama.2012.12505Oristrell, Oliva, Casado, Subirana, Domínguez et al., Vitamin D supplementation and COVID-19 risk: A population-based, cohort study, J. Endocrinol. Investig,
doi:10.1007/s40618-021-01639-9Perticone, Maio, Sciacqua, Suraci, Pinto et al., Ketogenic Diet-Induced Weight Loss is Associated with an Increase in Vitamin D Levels in Obese Adults, Molecules
Quraishi, Camargo, Vitamin D in acute stress and critical illness, Curr. Opin. Clin. Nutr. Metab. Care
Rybchyn, Abboud, Puglisi, Gordon-Thomson, Brennan-Speranza et al., Skeletal Muscle and the Maintenance of Vitamin D Status, Nutrients,
doi:10.3390/nu12113270Sabetta, Depetrillo, Cipriani, Smardin, Burns et al., Serum 25-hydroxyvitamin d and the incidence of acute viral respiratory tract infections in healthy adults, PLoS ONE,
doi:10.1371/journal.pone.0011088Sanghera, Sapkota, Aston, Blackett, Vitamin et al., Gender Differences and Cardiometabolic Health Disparities, Ann. Nutr. Metab,
doi:10.1159/000458765Shirvaliloo, Epigenomics in COVID-19; the link between DNA methylation, histone modifications and SARS-CoV-2 infection, Epigenomics,
doi:10.2217/epi-2021-0057Thacher, Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19, Nutrients,
doi:10.3390/nu14030464Wang, Chen, Li, Yin, Zhang et al., Vitamin D and Chronic Diseases, Aging Dis
Wortsman, Matsuoka, Chen, Lu, Holick, Decreased bioavailability of vitamin D in obesity, Am. J. Clin. Nutr,
doi:10.1093/ajcn/72.3.690Zdrenghea, Makrinioti, Bagacean, Bush, Johnston et al., Vitamin D modulation of innate immune responses to respiratory viral infections, Rev. Med. Virol,
doi:10.1002/rmv.1909Ziaie, Razmjou, Jomhouri, Jenabi, Vitamin D Toxicity; Stored and Released from Adipose Tissue?, Arch. Iran. Med
