The Association Between COVID-19 and Herpes Zoster in Adult Populations: A Systematic Review

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), has been associated with a wide range of dermatological manifestations. Herpes zoster (HZ), also known as shingles, has been increasingly reported in adults with COVID‑19 infection. Several reports suggest that SARS‑CoV‑2-associated immune dysregulation, particularly lymphopenia and impaired T-cell-mediated immunity, may contribute to varicella-zoster virus (VZV) reactivation. This systematic review aimed to evaluate the temporal relationship between COVID‑19 infection and shingles rash, including the onset, clinical outcomes, prognostic implications, recovery, and relationship with lymphopenia. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature review was conducted using PubMed, MEDLINE and Cochrane databases for studies published within the last five years. Search terms included "COVID‑19", "SARS-CoV-2", "herpes zoster" and "shingles rash". Inclusion criteria consisted of case reports, case series, cohort studies, systematic reviews, and research studies. Studies included were in the English language. Studies not relevant to the research question, paediatric cohorts, or commenting on vaccination were excluded. Fifty-seven studies (N=57) were initially identified through database search, with 35 studies (N=35) deemed relevant to the research question following screening. Twenty-five studies (N=25) were excluded due to data not being relevant to the research question, paediatric cohort data, or vaccination-related data. After exclusion, 10 studies (N=10) were included in the review for qualitative analysis. Most studies demonstrated a temporal association between COVID‑19 infection and HZ occurrence. HZ rash developed from two days before COVID‑19 symptoms and up to 70 days after infection, with an average onset approximately 17 days after COVID‑19 diagnosis. Several studies reported that HZ preceded or coincided with COVID‑19 symptoms, suggesting that shingles may serve as an early indicator of SARS‑CoV‑2 infection. Associated lymphopenia was noted, suggesting that COVID-19-induced immune dysregulation contributes to VZV reactivation. Most patients recovered from HZ rash following antiviral therapy, although severe complications and prolonged hospitalisation were observed in cases involving co-infection and systemic disease. Overlooking this possible association may result in an undiagnosed COVID-19 infection in those presenting with shingles rash and a higher risk of developing long COVID. The reviewed studies indicate that COVID-19 may be associated with HZ reactivation in the general adult population, although causality remains unproven. This detailed data analysis and systematic review demonstrate that evidence is scarce in this domain, which warrants larger epidemiological and immunological studies as well as further meta-analyses to determine the prognostic significance of shingles rash in COVID‑19 infection, in particular long COVID.