Long-term risk of herpes zoster following COVID-19: A retrospective cohort study of 2 442 686 patients.

The long-term risk of herpes zoster (HZ) after recovery from a SARS-CoV-2 infection is unclear. This retrospective cohort study assessed the risk of HZ in patients following a COVID-19 diagnosis. This retrospective, propensity score-matched cohort study was based on the multi-institutional research network TriNetX. The risk of incident HZ in patients with COVID-19 was compared with that of those not infected with SARS-CoV-2 during a 1-year follow-up period. Hazard ratios (HRs) and 95% confidence intervals (CIs) of HZ and its subtypes were calculated. This study identified 1 221 343 patients with and without COVID-19 diagnoses with matched baseline characteristics. During the 1-year follow-up period, patients with COVID-19 had a higher risk of HZ compared with those without COVID-19 (HR: 1.59; 95% CI: 1.49-1.69). In addition, compared with the control group patients, those with COVID-19 had a higher risk of HZ ophthalmicus (HR: 1.31; 95% CI: 1.01-1.71), disseminated zoster (HR: 2.80; 95% CI: 1.37-5.74), zoster with other complications (HR: 1.46; 95% CI: 1.18-1.79), and zoster without complications (HR: 1.66; 95% CI: 1.55-1.77). Kaplan-Meier curve analysis (log-rank p < 0.05) results indicated that the risk of HZ remained significantly higher in patients with COVID-19 compared with those without COVID-19. Finally, the higher risk of HZ in the COVID-19 cohort compared with that in the non-COVID-19 cohort remained consistent across subgroup analyses regardless of vaccine status, age, or sex. The risk of HZ within a 12-month follow-up period was significantly higher in patients who had recovered from COVID-19 compared with that in the control group. This result highlights the importance of carefully monitoring HZ in this population and suggests the potential benefit of the HZ vaccine for patients with COVID-19.

Risk of Herpes Zoster in Patients with Pulmonary Tuberculosis-A Population-Based Cohort Study.

BACKGROUND: Pulmonary tuberculosis (TB), a global health problem, is typically caused by the bacterium Mycobacterium tuberculosis. Herpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus (VZV). The reactivation of VZV can be caused by stress. We investigated whether pulmonary TB increases the risk of HZ development. METHODS: This study used data that sampled a population of 2 million people in 2000 from the National Health Insurance Research Database. This cohort study observed Taiwanese patients aged 20-100 years with pulmonary TB from 2000 to 2017 (tracked to 2018). Pulmonary TB was defined as having two or more outpatient diagnoses or at least one admission record. To address potential bias caused by confounding factors, the control cohort and pulmonary TB cohort were matched 1:1 by age, gender, index year, and comorbidities. Patients with HZ before the index date were excluded. RESULTS: A total of 30,805 patients were in the pulmonary TB and control cohorts. The incidence rate of HZ in pulmonary TB and control cohorts were 12.00 and 9.66 per 1000 person-years, respectively. The risk of HZ in the pulmonary TB cohort (adjusted hazard ratios = 1.23; 95% confidence interval = 1.16-1.30) was significantly higher than that of in control cohort. Among patients without comorbidities, the patients with TB were 1.28-fold more likely to have HZ than those without TB. CONCLUSION: Patients with TB should be well treated to avoid the potential risk of HZ occurrence. Although we identified the association between pulmonary TB and HZ, further studies are needed to confirm the result.

Predictors of herpes zoster vaccination among Australian adults aged 65 and over.

OBJECTIVE(S): To estimate HZ vaccine coverage in Australia among older Australians and to identify potential barriers to vaccination. DESIGN: Analysis of data from three cross-sectional surveys administered online between 2019 and 2020. SETTING AND PARTICIPANTS: Adults aged 65 and over residing in Australia. MAIN OUTCOME MEASURES: Self-reported herpes zoster vaccination. RESULTS: Among the 744 adults aged 65 and over in this sample, 32% reported being vaccinated for HZ, including 23% of participants aged 65-74, 55% of participants aged 75-84, and 0% for participants aged 85 and above. Those who are vaccinated with other immunisations are more likely to have received HZ vaccine, including seasonal influenza (OR = 4.41, 95 % CI: 2.44-7.98) and pneumococcal vaccines (OR = 4.43, 95 % CI: 2.92 - 6.75). Participants with a history of certain conditions, such as stroke (OR = 2.26, 95 % CI: 1.13-4.49), were more likely to be vaccinated against HZ. Participants that reported smoking tobacco daily were less likely to be vaccinated against HZ (OR = 0.48, 95 % CI: 0.26-0.89). Participants were less likely to be vaccinated against HZ if they preferred to develop immunity 'naturally' (OR = 0.29, 95 % CI: 0.15 - 0.57) or expressed distrust of vaccines (OR = 0.34, 95 % CI: 0.13-0.91). CONCLUSION(S): Further research is required to understand the barriers to HZ vaccine uptake. Increasing the funding eligibility for those who are at risk of complications from shingles, or lowering the age of eligibility, may increase vaccine coverage.

Willingness to accept herpes zoster vaccines and the influencing factors in China.

BACKGROUND: Herpes zoster increases the burden on the elderly in an aging society. Although an effective vaccine licensed by China Food and Drug Administration in 2019 was introduced into the market in June 2020, the willingness and influencing factors of herpes zoster vaccines in Chinese adults ≥ 50-years-old during coronavirus disease-2019 pandemic are yet to be elucidated. METHODS: An online questionnaire survey was conducted using a simple random sampling method in October 2021 for viewers of the broadcast program. A binary logistic regression and multiple response analysis were conducted for herpes zoster vaccine and vaccination willingness. Pareto's graphs were plotted to present the multiple-choice questions of influencing factors. RESULTS: A total of 3838 eligible participants were included in this study. Among them, 43.02% intended to be vaccinated, including 10.34% self-reported about receiving at least one shot of shingles vaccine, 30.22% declined, and 26.76% were hesitant. This population comprised a large proportion of middle-aged and older people (≥ 50-years-old) who have not experienced an episode of herpes zoster (54.98%) or are unaware of the virus (33.22%). The strongest determinants of vaccine hesitancy among older people were education background of Master's degree or above compared to senior high or equivalent and below, personal monthly income < 3000 RMB compared to 3000-5999 RMB, and living in a rural area. CONCLUSIONS: The willingness to get shingles vaccines can be improved further. Professional education and credible recommendation might prompt the elderly to improve their willingness and reassure them of the safety and efficacy of the vaccine. Also, accessibility and affordability should also be improved in the future.

Assessment of Herpes Zoster Risk Among Recipients of COVID-19 Vaccine.

Importance: Herpes zoster infection after COVID-19 vaccination has been reported in numerous case studies. It is not known whether these cases represent increased reporting or a true increase in risk. Objective: To assess whether COVID-19 vaccination is associated with an increased risk of herpes zoster infection. Design, Setting, and Participants: This cohort study used a self-controlled risk interval (SCRI) design to compare the risk of herpes zoster in a risk interval of 30 days after COVID-19 vaccination or up to the date of the second vaccine dose with a control interval remote from COVID-19 vaccination (defined as 60-90 days after the last recorded vaccination date for each individual, allowing for a 30-day washout period between control and risk intervals). A supplemental cohort analysis was used to compare the risk of herpes zoster after COVID-19 vaccination with the risk of herpes zoster after influenza vaccination among 2 historical cohorts who received an influenza vaccine in the prepandemic period (January 1, 2018, to December 31, 2019) or the early pandemic period (March 1, 2020, to November 30, 2020). Data were obtained from Optum Labs Data Warehouse, a US national deidentified claims-based database. A total of 2 039 854 individuals who received any dose of a COVID-19 vaccine with emergency use authorization (BNT162b2 [Pfizer-BioNTech], mRNA-1273 [Moderna], or Ad26.COV2.S [Johnson & Johnson]) from December 11, 2020, through June 30, 2021, were eligible for inclusion. Individuals included in the SCRI analysis were a subset of the COVID-19-vaccinated cohort who had herpes zoster during either a risk or control interval. Exposures: Any dose of a COVID-19 vaccine. Main Outcomes and Measures: Incident herpes zoster, defined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes and a prescription of a new antiviral medication or a dose increase in antiviral medication within 5 days of diagnosis. Results: Among 2 039 854 individuals who received any dose of a COVID-19 vaccine during the study period, the mean (SD) age was 43.2 (16.3) years; 1 031 149 individuals (50.6%) were female, and 1 344 318 (65.9%) were White. Of those, 1451 patients (mean [SD] age, 51.6 [12.6] years; 845 [58.2%] female) with a herpes zoster diagnosis were included in the primary SCRI analysis. In the SCRI analysis, COVID-19 vaccination was not associated with an increased risk of herpes zoster after adjustment (incidence rate ratio, 0.91; 95% CI, 0.82-1.01; P = .08). In the supplementary cohort analysis, COVID-19 vaccination was not associated with a higher risk of herpes zoster compared with influenza vaccination in the prepandemic period (first dose of COVID-19 vaccine: hazard ratio [HR], 0.78 [95% CI, 0.70-0.86; P < .001]; second dose of COVID-19 vaccine: HR, 0.79 [95% CI, 0.71-0.88; P < .001]) or the early pandemic period (first dose of COVID-19 vaccine: HR, 0.89 [95% CI, 0.80-1.00; P = .05]; second dose: HR, 0.91 [95% CI, 0.81-1.02; P = .09]). Conclusions and Relevance: In this study, there was no association found between COVID-19 vaccination and an increased risk of herpes zoster infection, which may help to address concerns about the safety profile of the COVID-19 vaccines among patients and clinicians.

Varicella zoster meningitis following COVID-19 vaccination: a report of two cases.

Most of the adverse effects reported in patients who have received COVID-19 vaccines have been mild. However, possible serious adverse effects are being monitored cautiously. There have also been a number of case reports of reactivation of varicella zoster infection within 28 days after immunization with mRNA COVID-19 vaccines. A few cases have also been reported after viral vector and inactivated COVID-19 vaccination. The incidence of meningitis following varicella zoster virus infection is rare. In the current study, we report two cases of male patients who received two different types of COVID-19 vaccine (inactivated and viral vector) and developed varicella zoster meningitis within 10 days after vaccination.

Characteristics of herpes zoster infection in patients with COVID-19: a systematic scoping review.

BACKGROUND: Although there is literature reporting correlations between varicella zoster virus (VZV) infections and COVID-19, insufficient evidence exists in this regard. This scoping review aims to identify the existing evidence regarding clinical characteristics of primary VZV infection or reactivation in COVID-19. METHODS: Following the PRISMA Extension for Scoping Reviews, MEDLINE and EMBASE were searched for all peer-reviewed articles with relevant keywords including "Zoster," "Herpes," and "COVID-19" from their inception to November 20, 2021. RESULTS: A total of 19 articles with three observational studies and 16 case reports or series were included. Primary VZV infections or reactivation were observed in 25 patients. Forty-eight percent of the patients had disseminated VZV infection. The median time of VZV-related rash after the onset of respiratory symptoms was 7.0 days (interquartile range: 0-18.8). Those with COVID-19 and primary VZV infection or reactivation had low lymphocyte counts with a median of 0.67 × 103 /µl. CONCLUSION: This scoping review identified uncertainty and a lack of strong evidence to see the association between primary VZV infection or reactivation and COVID-19. However, those with COVID-19 may be more likely to have disseminated VZV, which poses an additional challenge from an infection prevention standpoint. Future studies are warranted to determine the association between primary VZV infection or reactivation and long-term consequences related to COVID-19.

Real-world evidence from over one million COVID-19 vaccinations is consistent with reactivation of the varicella-zoster virus.

BACKGROUND: Reactivation of the varicella-zoster virus (VZV), which causes herpes zoster (HZ, synonym: shingles) in humans, can be a rare adverse reaction to vaccines. Recently, reports of cases after COVID-19 vaccination have arisen. OBJECTIVES: The aim of this study was to assess whether the frequency of HZ is found to increase after COVID-19 vaccination in a large cohort, based on real-world data. As a hypothesis, the incidence of HZ was assumed to be significantly higher in subjects who received a COVID-19 vaccine (Cohort I) vs. unvaccinated individuals (Cohort II). METHODS: The initial cohorts of 1 095 086 vaccinated and 16 966 018 unvaccinated patients were retrieved from the TriNetX database and were matched on age and gender in order to mitigate confounder bias. RESULTS: After matching, each cohort accounted for 1 095 086 patients. For the vaccinated group (Cohort I), 2204 subjects developed HZ within 60 days of COVID-19 vaccination, while among Cohort II, 1223 patients were diagnosed with HZ within 60 days after having visited the clinic for any other reason (i.e. not vaccination). The risk of developing shingles was calculated as 0.20% and 0.11% for cohort I and cohort II, respectively. The difference was statistically highly significant (P < 0.0001; log-rank test). The risk ratio and odds ratio were 1.802 (95% confidence interval [CI] = 1.680; 1.932) and 1.804 (95% CI = 1.682; 1.934). CONCLUSIONS: Consistent with the hypothesis, a higher incidence of HZ was statistically detectable post-COVID-19 vaccine. Accordingly, the eruption of HZ may be a rare adverse drug reaction to COVID-19 vaccines. Even though the molecular basis of VZV reactivation remains murky, temporary compromising of VZV-specific T-cell-mediated immunity may play a mechanistic role in post-vaccination pathogenesis of HZ. Note that VZV reactivation is a well-established phenomenon both with infections and with other vaccines (i.e. this adverse event is not COVID-19-specific).

Herpes zoster in the era of COVID 19: A prospective observational study to probe the association of herpes zoster with COVID 19 infection and vaccination.

Herpes zoster (HZ) is caused by reactivation of the latent varicella zoster virus (VZV) following decline in cell-mediated immunity. All over the world, in the past couple of years, the Corona Virus 2019 (COVID-19) has emerged as a viral cause of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection. Based on the current limited evidence, co-infection of COVID-19 with VZV or reactivation of VZV after COVID-19 vaccination has been sporadically reported. All patients diagnosed with HZ, in Farwaniya Hospital in Kuwait, from March 2020 to July 2021, having either (A) a positive COVID-19 polymerase chain reaction (PCR) test, or (B) been vaccinated against SARS-CoV-2 were enrolled in the study. All patients' demographic information, medical history, laboratory findings, and vaccination status was documented. All statistical analyses were performed using SPSS Statistics version 21.0 software. Twelve cases infected with COVID-19 with a positive PCR (group 1) and five cases vaccinated against SARS-CoV-2 (group 2) were documented. Out of the 12 COVID-19 infected patients (group 1), only two patients (16.67%) required hospitalization, while the remaining 10 patients had mild/moderate lymphopenia. Furthermore, amongst the 12 positive COVID-19 cases, four patients with HZ were diagnosed within the first week of COVID-19, while the remaining eight cases were diagnosed within 8 weeks of COVID-19. Thoracic segments were affected in five cases (41.67%), cervical in one case (8.33%), cranial in two cases (16.67%), lumbar in three cases (25%) and sacral in one case (8.33%). In group 2, three patients presented with HZ within 4 weeks of having received the first dose of the vaccine and two patients after the second dose. Blood investigations for all five vaccinated patients did not show any abnormalities. Cervical segments were affected in two patients (40%), and cranial, thoracic, and lumbar segment in the remaining patients respectively (20%). Experts must be aware of the probable increased risk of HZ during the COVID 19 pandemic. We propose appropriate curative and preventive measures against HZ infection, including a systematic follow-up of these patients to ensure that they stick to extreme safety measures till the diagnosis of COVID-19 is omitted.

Herpes zoster following vaccination with ChAdOx1 nCoV-19 Coronavirus vaccine (recombinant).

Ever since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, science has unraveled much knowledge on SARS-CoV-2 which has led to extraordinary and unprecedented progress in developing COVID-19 vaccines. Several adverse cutaneous reactions, ranging from more common local injection site reaction, neutrophilic and pustular drug reactions to flare-up of preexisting dermatoses, have been reported with currently available vaccines. We report a case series of 7 patients who developed herpes zoster (HZ) following the first dose of ChAdOx1 nCoV-19 coronavirus vaccine (recombinant). HZ following vaccination is a rare entity. The occurrence of HZ in the patients presented in this series within the time window 1-21 days after vaccination defined for increased risk and postulated dysregulation of T-cell-mediated immunity, suggests that the ChAdOx1 nCoV-19 coronavirus vaccine (recombinant) could probably be a trigger for reactivation of varicella zoster virus to cause HZ in them.

Recombinant Adjuvanted Zoster Vaccine and Reduced Risk of Coronavirus Disease 2019 Diagnosis and Hospitalization in Older Adults.

BACKGROUND: Some vaccines elicit nonspecific immune responses that may protect against heterologous infections. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and coronavirus disease 2019 (COVID-19) outcomes at Kaiser Permanente Southern California. METHODS: In a cohort design, adults aged ≥50 years who received ≥1 RZV dose before 1 March 2020 were matched 1:2 to unvaccinated individuals and followed until 31 December 2020. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive severe acute respiratory syndrome coronavirus 2 test and controls had only negative tests, during 1 March-31 December 2020. Adjusted odds ratios (aORs) and 95% CIs for RZV receipt were estimated using logistic regression. RESULTS: In the cohort design, 149 244 RZV recipients were matched to 298 488 unvaccinated individuals. The aHRs for COVID-19 diagnosis and hospitalization were 0.84 (95% CI, .81-.87) and 0.68 (95% CI, .64-.74), respectively. In the test-negative design, 8.4% of 75 726 test-positive cases and 13.1% of 340 898 test-negative controls had received ≥1 RZV dose (aOR, 0.84 [95% CI, .81-.86]). CONCLUSIONS: RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization. Further study of vaccine-induced nonspecific immunity for potential attenuation of future pandemics is warranted.

Herpes zoster and simplex reactivation following COVID-19 vaccination: new insights from a vaccine adverse event reporting system (VAERS) database analysis.

BACKGROUND: A few cases of Herpes Zoster and Simplex reactivation following COVID-19 immunization have been recently described, but the real extent of this suspected adverse event has not been elucidated yet. METHODS: We performed a nested case/control study by using the U.S. Vaccine Adverse Event Reporting System database. We carried out a case-level clinical review of all Herpes reactivation cases following the administration of COVID-19 vaccines. For cases and controls, significance was set at P = 0.05, differential risk of reporting was assessed for each vaccine as reporting odds ratio and incidence was estimated based on the total number of vaccine doses administered. RESULTS: Of 6,195 cases included in the analysis (5,934 and 273 reporting Herpes Zoster and Herpes Simplex, respectively) over 90% were non-serious. We found a slightly higher risk of reporting both for Zoster (ROR = 1.49) and Simplex (ROR = 1.51) infections following the Pfizer-BioNTech vaccine. The estimated incidence was approximately 0.7/100,000 and 0.03/100,000 for Zoster and Simplex, respectively. CONCLUSIONS: The paucity of cases (almost all of non-serious nature) makes the potential occurrence of this adverse effect negligible from clinical standpoints, thus supporting the good safety profile of the COVID-19 vaccination, which remains strongly recommended.

Association study between herpes zoster reporting and mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273).

Several cases of herpes zoster (HZ) following mRNA COVID-19 vaccination (BNT162b2 and mRNA-1273) have been reported, and the first epidemiological evidence suggests an increased risk. We used the worldwide pharmacovigilance database VigiBase to describe HZ cases following mRNA COVID-19 vaccination. We performed disproportionality analyses (case/non-case statistical approach) to assess the relative risk of HZ reporting in mRNA COVID-19 vaccine recipients compared to influenza vaccine recipients and according to patient age. To 30 June 2021, of 716 928 reports with mRNA COVID-19 vaccines, we found 7728 HZ cases. When compared to influenza vaccines, mRNA COVID-19 vaccines were associated with a significantly higher reporting of HZ (reporting odds ratio 1.9, 95% CI 1.8-2.1). Furthermore, we found a reduced risk of reporting HZ among under 40-year-old persons compared to older persons (reporting odds ratio 0.39, 95% CI 0.36-0.41). Mild and infrequent HZ reactions may occur shortly after mRNA COVID-19 vaccination, at higher frequency than reported with influenza vaccination, especially in patients over 40 years old. Further analyses are needed to confirm this risk.

Interplay between stress and immunity triggers herpes zoster infection in COVID-19 patients: a review.

Coronavirus disease 2019 (COVID-19) is a potential health threat in the highly mobile society of the world. There are also concerns regarding the occurrence of co-infections occurring in COVID-19 patients. Herpes zoster (HZ) is currently being reported as a co-infection in COVID-19 patients. It is a varicella-zoster virus induced viral infection affecting older and immunocompromised individuals. Reactivation of HZ infection in COVID-19 patients are emerging and the mechanism of reactivation is still unknown. The most convincing argument is that increased psychological and immunological stress leads to HZ in COVID-19 patients; this review justifies this argument.

Association of COVID-19 vaccination with herpes zoster: a systematic review and meta-analysis.

BACKGROUND: Following COVID-19 vaccination, several herpes zoster cases have been reported, making it critical to explore the association between herpes zoster and COVID-19 vaccination. This is especially true in the context of increasing the number of participants enrolled to receive COVID-19 vaccination. RESEARCH DESIGN AND METHODS: Three databases, including the Cochrane Library, PubMed, and EMBASE, were searched for relevant studies before 25 December 2021 according to preliminarily determined inclusion and exclusion criteria without any language limitations. Four cohort studies were included in this systematic review and meta-analysis. RESULTS: Compared with the placebo group, there was no evidence that the COVID-19 vaccination group was associated with increased incidence of herpes zoster (Risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.91 to 1.24). There is no evidence that the COVID-19 vaccination from Moderna is associated with the incidence of herpes zoster compared with vaccination from Pfizer (RR: 0.20; 95% CI: 0.01 to 2.99). CONCLUSIONS: To date, there is no evidence of an association between covid-19 vaccination and herpes zoster.

Modeled impact of the COVID-19 pandemic and associated reduction in adult vaccinations on herpes zoster in the United States.

Due to COVID-19, vaccinations dropped in 2020 and 2021. We estimated the impact of reduced recombinant zoster vaccine (RZV) use on herpes zoster (HZ) cases, complications, and quality-adjusted life-year (QALY) losses among older adults. Various scenarios were compared with Markov models using data from national sources, clinical trials, and literature. Missed series initiations were calculated based on RZV distributed doses. In 2020, 3.9 million RZV series initiations were missed, resulting in 31,945 HZ cases, 2,714 postherpetic neuralgia cases, and 610 lost QALYs. Scenarios further projected disease burden increases if individuals remain unvaccinated in 2021 or the same number of initiations are missed in 2021. Health professionals should emphasize the importance of vaccination against all preventable diseases during the COVID-19 era.