Increased risk of herpes zoster hospitalization after COVID-19 vaccination

A self-controlled case series reported by researchers from the University of Hong Kong has identified an increased risk of herpes zoster–related hospitalization associated with mRNA-based BNT162b2 and inactivated CZ02 vaccination against coronavirus disease 2019 (COVID-19).

“The emergency approval of COVID-19 vaccines requires close monitoring for adverse events following immunization. After the launch of mass vaccination, over 6,000 and 2,500 herpes zoster cases have been reported through the Vaccine Adverse Event Reporting System in the US and Yellow Card reports by the Medicines and Healthcare Products Regulatory Agency in the UK, respectively,” wrote the researchers. [http://wonder.cdc.gov/vaers.html; https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting] “Our study aimed to evaluate the risk of herpes zoster–related hospitalization following BNT162b2 and CZ02 vaccination using population-based electronic healthcare records in Hong Kong.”

Between 23 February and 31 July 2021, a total of 3,409,470 doses of BNT162b2 and 2,251,829 doses of CZ02 were administered. The number of herpes zoster–related hospitalizations within 28 days after the first or second dose of BNT162b2 or CZ02 was 27 and 16, respectively. Therefore, the incidence of hospitalization due to herpes zoster was 7.9 (95 percent confidence interval [CI], 5.2 to 11.5) per 1,000,000 doses of BNT162b2 and 7.1 (95 percent CI, 4.1 to 11.5) per 1,000,000 doses of CZ02. [Lancet Reg Health West Pac 2022;doi:10.1016/j.lanwpc.2022.100393]

Among patients who received BNT162b2, the average duration of herpes zoster–related hospitalization was 3.78 days, and two patients (7.41 percent of those hospitalized for herpes zoster) experienced recurrent hospitalization due to herpes zoster. Among the affected CZ02 recipients, the average duration of herpes zoster–related hospitalization was 4.06 days, and only one patient (6.25 percent) had recurrent hospitalization.

“Previously, there have been reports of herpes zoster reactivation after inactivated influenza, hepatitis A, rabies, and Japanese encephalitis vaccination,” noted the researchers. “While herpes zoster usually manifests as a self-limiting dermatomal rash with pain, about 20 percent of cases may develop postherpetic neuralgia, and around 2 percent of cases may have various fatal complications including transient ischaemic attacks, stroke and myocardial infarction.” [Lancet 1999;353:810; Stroke 2009;40:3443-3448; Mayo Clin Proc 2019;94:763-775]

The self-controlled case series analysis involved 545 patients hospitalized with herpes zoster, of whom 91 patients were vaccinated and 454 were unvaccinated. BNT162b2 vaccination was associated with a significantly higher risk of herpes zoster–related hospitalization after the first dose and until 14 days following the second dose (0–13 days after first dose: adjusted incidence rate ratio [aIRR], 5.23; 95 percent CI, 1.61 to 17.03) (14–27 days after first dose: aIRR, 5.82; 95 percent CI, 1.62 to 20.91) (0–13 days after second dose: aIRR, 5.14; 95 percent CI, 1.29 to 20.47). CZ02 vaccination was associated with a significantly increased risk of herpes zoster–related hospitalization within 14 days after the first dose (aIRR, 2.67; 95 percent CI, 1.08 to 6.59), but not in subsequent periods vs baseline.

“Given the relative risk of around 5 after BNT162b2 and 3 after CZ02 vaccination, it was deduced that an additional 5 and 7 cases of herpes zoster–related hospitalization may occur for every 1,000,000 doses of CZ02 and BNT162b2, respectively, vs no vaccination,” summarized the researchers. “However, the protective effects of vaccinations in reducing the risk of severe COVID-19 greatly outweigh the potential side effects of BNT162b2 and CZ02 vaccination, including a slight increase in risk of herpes zoster.”