The association between vitamin D deficiency and the risk of herpes zoster and COVID-19

BACKGROUND: Acute viral infections or reactivations, such as Coronavirus Disease 2019 (COVID-19) and herpes zoster (HZ), can cause high morbidity and mortality among older adults. Although vitamin D has immunomodulatory effects, the association between vitamin D status and COVID-19 and HZ is unclear. In this thesis, I investigated the association between vitamin D deficiency and HZ and COVID-19. METHODS: This thesis comprises four parts: one systematic review and three analytic studies using UK Biobank. First, I systematically reviewed studies about vitamin D and human herpesviruses infection or reactivation. Second, I conducted a cross-sectional study which described the distribution of vitamin D status and identified demographic risk factors for vitamin D deficiency and insufficiency in UK Biobank. In the third part, I undertook a cohort study to explore the association between vitamin D status, supplementation, and prescriptions and the risk of incident HZ. Finally, I assessed the association between vitamin D status and COVID-19 diagnosis, hospitalisation, and mortality. RESULTS: My systematic review and meta-analysis (Chapter 3) included ten studies, and the results demonstrated that vitamin D deficiency was not associated with cytomegalovirus (CMV) diseases in transplant patients, but vitamin D supplementation was associated with a lower risk of HZ in individuals receiving haemodialysis. All included studies were hospital-based and conducted among immunosuppressed people. In my cross-sectional study (Chapter 5) of 449,943 participants aged 40 to 69 years with vitamin D records, I found that the winter and spring seasons, northern regions, male sex, abnormal body mass index (BMI), non-white ethnic backgrounds, smoking, and socioeconomic deprivation were associated with vitamin D deficiency and insufficiency. My cohort study of vitamin D and HZ (Chapter 6) included 177,572 participants with linked clinical records. I found no association between vitamin D deficiency and incident HZ (deficient: adjusted hazard ratio (HR) = 0.99, 95% confidence interval (CI) = 0.90–1.10). Vitamin D supplementation or prescriptions were not associated with incident HZ. Finally, in the cohort study of vitamin D and COVID-19 (Chapter 7), including 307,512 people with linked COVID-19 clinical records, I found an inconsistent association between vitamin D deficiency and COVID-19 diagnosis during different follow-up periods (during British summertime (BST) months: HR=0.86, 95% CI=0.77–0.95; during non-BST months: HR=1.14, 95%CI=1.01– 1.30). I found no evidence that vitamin D deficiency or insufficiency was associated with either hospitalisation or mortality due to COVID-19 in any time stratum. CONCLUSION: In summary, I found no association between vitamin D status, supplementation, or prescriptions and the risk of HZ or COVID-19. According to currently available evidence, extra vitamin D supplementation should not be recommended to prevent HZ or COVID- 19.