Increased Risk of Herpes Zoster in Adults ≥50 Years Old Diagnosed With COVID-19 in the United States

Abstract

Background: Case reports have described herpes zoster (HZ) in patients with coronavirus disease 2019 (COVID-19). However, this constitutes low-quality evidence for an association. We therefore performed a retrospective cohort study to assess the risk of developing HZ following a COVID-19 diagnosis.

Methods: We compared the HZ incidence in ≥50-year-olds diagnosed with COVID-19 vs those never diagnosed with COVID-19. We used data from the US MarketScan Commercial Claims and Encounters and Medicare Supplemental (3/2020-2/2021) and Optum Clinformatics Data Mart (3-12/2020) databases. Individuals with COVID-19 were exact-matched 1:4 to those without COVID-19 by age, sex, presence of HZ risk factors, and health care cost level. Adjusted incidence rate ratios (aIRRs) were estimated by Poisson regression.

Results: A total of 394 677 individuals ≥50 years old with COVID-19 were matched with 1 577 346 individuals without COVID-19. Mean follow-up time after COVID-19 diagnosis and baseline characteristics were balanced between cohorts. Individuals diagnosed with COVID-19 had a 15% higher HZ risk than those without COVID-19 (aIRR, 1.15; 95% CI, 1.07-1.24; P < .001). The increased HZ risk was more pronounced (21%) following COVID-19 hospitalization (aIRR, 1.21; 95% CI, 1.03-1.41; P = .02).

Conclusions: We found that COVID-19 diagnosis in ≥50-year-olds was associated with a significantly increased risk of developing HZ, highlighting the relevance of maintaining HZ vaccination.

Keywords: COVID-19; SARS-CoV-2; coronavirus; herpes zoster; shingles.

Graphical abstract

Figure 1.

Disposition of individuals in the COVID-19_50+ and non-COVID-19_50+ cohorts. ^aEligible for matching were those with ≥1 day of follow-up after March 13, 2020, and ≥365 days until March 13, 2020, no history of HZ, HZ vaccination, or COVID-19 vaccination until March 13, 2020, and no estimated negative total cost (in inpatient, outpatient, and pharmacy claims) during the 183 days before March 13, 2020. Further exclusions based on history of HZ, HZ vaccination, or COVID-19 vaccination until the index date were only done at the time of matching (when the index date was determined). ^bFour matches were identified for each individual with COVID-19, but not all had follow-up time beyond the index date; the latter were therefore not part of the matched non-COVID-19_50+ cohort. Abbreviations: COVID-19, coronavirus disease 2019; COVID-19_50+, cohort of individuals ≥50 years old with a first-time COVID-19 diagnosis during the study period; non-COVID-19_50+, cohort of individuals ≥50 years old with no history of COVID-19, clinically–epidemiologically diagnosed COVID-19, probable COVID-19, or suspected COVID-19 at any time, matched to individuals in the COVID-19_50+ cohort; HZ, herpes zoster; n, number of individuals remaining at the indicated step.

Figure 2.

Relative risk of HZ in individuals diagnosed with COVID-19 vs those never diagnosed with COVID-19 (or with vs without fractures). Bold formatting indicates statistical significance. All analyses were on individuals ≥50 years old diagnosed with COVID-19 vs those never diagnosed with COVID-19, unless when otherwise stated. ^aAdjusted for sex, age category, and log(cost during 1 year before index + 1). For the sensitivity analysis on fractures, the standardized mean difference for log(cost during 1 year before index + 1) between the fracture and nonfracture cohorts was just below 0.20, but the variable was still included in the model for consistency with the main analyses. ^bAdjusted for sex and log(cost during 1 year before index + 1). Diabetes before the index date and diabetes before March 13, 2020, were considered for inclusion in the model because of an observed imbalance but were discarded due to nonsignificant effects. ^cAdjusted for sex, log(cost during 1 year before index + 1), and interaction between cohort and age category. Analysis was produced based on the population ≥18 years old. Abbreviations: COVID-19, coronavirus disease 2019; days, days after the index date; HZ, herpes zoster.