Vitamin D deficiency or supplementation and the risk of human herpesvirus infections or reactivation: a systematic review protocol

Abstract

IntroductionHuman herpesviruses induce lifelong latent infections and may reactivate as the immune system deteriorates. Recent studies have suggested that vitamin D, an essential element of bone health, may have some effect of protecting against infections, but investigations of its potential to prevent herpesvirus infection or reactivation are limited. We will review the current literature examining vitamin D and the risk of herpesvirus infections or reactivation.Methods and analysisOur systematic review will address two research questions: (1) Do deficient/insufficient serum vitamin D levels increase the risk of herpesvirus infections and (2) Does vitamin D supplementation protect against herpesvirus infections? We will include only intervention studies with control groups, cohort studies and case-control studies. We will use subject headings and keywords to search for synonyms of ‘vitamin D’ and ‘herpesviruses’ (including herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus and human herpesviruses type 6, 7 and 8) in Medline, Embase, Global Health, Web of Science, Scopus and Cochrane Central Register of Controlled Trials, and the grey literature databases Open Grey, EThOS and BASE from inception to 31 August 2019. References to the included articles and relevant systematic reviews will also be examined. Two reviewers will independently screen the study titles and abstracts, and examine the full texts to decide the final eligibility. They will independently extract data from the studies and assess bias using the Cochrane Collaboration approach. A third researcher will solve any discrepancies. The results will be narratively synthesised; if an adequate number of studies is included and the homogeneity between studies is acceptable, a meta-analysis will be performed. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework, and display the results in a summary of findings table.Ethics and disseminationEthical review is not required for a systematic review. We will publish the results in a peer-review journal. Any amendments to the protocol will be recorded in the supplementary section.PROSPERO registration numberCRD42019130153.

Vitamin D Deficiency or Supplementation and the Risk of Human Herpesvirus Infections or Reactivation: A Systematic Review and Meta-analysis

“…The protocol of this study has been previously registered on PROSPERO (registration number: CRD42019130153) and published [ 17 ].…”

“…As previously described, we included only human studies in our review [ 17 ]. The exposures were serum vitamin D deficiency or oral vitamin D supplementation, including vitamin D analog treatment.…”

Assessment of vitamin D levels in zona zoster

“…Defensins can also inhibit viral replication and cause direct degradation of the viral membrane [12]. After pathogen exposure, monocytes and macrophages increase the number of vitamin D receptors to increase cathelicidin production [13,14]. Cathelicidin effectively inhibits herpes simplex virus type 1 and retrovirus replication in LL-37 peptide form.…”

“…Activation of B and T lymphocytes has been shown to result in VDR expression. In addition, 1,25-(OH) 2 -D stimulates T lymphocyte maturation, increases the regulatory T lymphocyte ratio, and plays a role in limiting inflammation triggered by microbial invasion [6,13]. HIV infection weakens VDR activity.…”

“…However, vitamin D itself exhibits antiviral effects in vitro [7]. In a study of the effects of vitamin D-related antimicrobial peptides on herpes viruses, cathelicidine was shown to reduce HSV-1 viral titers isolated from patients with keratoconjunctivitis [13]. It has been shown that vitamin D deficiency correlates with increased mental stress.…”