The Impact of the COVID-19 Pandemic on the Incidence of Herpes Zoster: A Narrative Literature Review.

Coronavirus disease 2019 (COVID-19) has had a broad impact on health services and health outcomes. During the pandemic, there were numerous reports of herpes zoster (HZ) in people with COVID-19 and in COVID-19 vaccine recipients. The aim of this review is to elucidate the global effects of the COVID-19 pandemic on HZ. It is postulated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces an immunosuppressive state that favours varicella zoster virus (VZV) reactivation. Three large cohort studies (a multinational study and studies from the USA and Spain) that excluded individuals vaccinated against HZ reported significantly increased risk of HZ following COVID-19 infection, especially in people aged ≥ 50 years. In contrast, a large study from Israel that did not consider HZ vaccination status reported no such increase. Cases of HZ following COVID-19 vaccination have been reported and may be the result of attenuated cell-mediated immunity. This phenomenon appears to vary by vaccine type. Some (but not all) large analyses have reported a significant positive relationship between receipt of mRNA vaccines for COVID-19 and development of HZ. These include analyses of health records databases in Israel and Hong Kong and of spontaneous case reports in the US Vaccine Adverse Event Reporting System (VAERS) database. Routine vaccinations, including shingles vaccine programmes, were disrupted by the COVID-19 pandemic. It is estimated that missed shingles vaccinations may have resulted in 63,117 avoidable HZ cases in the USA. Now that the World Health Organization has declared an end to the COVID-19 pandemic as a health emergency and routine vaccination services have resumed, there is a need to increase awareness of HZ and HZ vaccination.Graphical abstract available for this article.

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

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.

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.

A practitioner's guide to the recombinant zoster vaccine: review of national vaccination recommendations.

INTRODUCTION: The adjuvanted recombinant zoster vaccine (RZV) is currently licensed in over 30 countries for the prevention of herpes zoster (HZ) in adults aged ≥50 years. We conducted a review of available national guidelines or recommendations on RZV use to identify the similarities and differences and highlight any potential gaps. AREAS COVERED: National recommendations from ten countries (Austria, Canada, the Czech Republic, Germany, Ireland, Italy, Spain, the Netherlands, the UK and the USA) are summarized under the following seven topics: HZ vaccine preference, age group recommendations, considerations prior to vaccination, dose schedule, co-administration with other vaccines, vaccination of special populations, and vaccine safety profile. In seven of these countries, RZV is the preferred or the only recommended HZ vaccine. There were some differences in age group recommendations, reflecting evaluations dependent on public funding. There were also differences with respect to use in immunocompromised and other special populations. EXPERT OPINION: The high efficacy and anticipated public health impact of RZV led to expanded national recommendations for RZV vaccination compared to previous HZ recommendation in many countries. Possible areas that could be considered in future revisions of national recommendations, including use in immunocompromised adults ≥18 years, are also highlighted.

PLAIN LANGUAGE SUMMARYThe varicella-zoster virus causes chickenpox, usually in childhood. After the chickenpox episode, the virus remains in the body in a latent state and can reactivate later in life, causing herpes zoster, or shingles. Adults over 50 years of age or those who have a weakened immune system are more vulnerable to developing herpes zoster. Herpes zoster appears as a painful localized skin rash. While live attenuated vaccines against herpes zoster have existed for many years, a recombinant vaccine against herpes zoster (RZV) has recently become available in several countries. Guidelines issued by national health authorities or vaccination committees provide healthcare professionals with information on practical aspects of vaccination. However, given the novelty of the RZV vaccine, we identified such guidelines in only ten countries (Austria, Canada, the Czech Republic, Germany, Ireland, Italy, Spain, the Netherlands, the United Kingdom, and the United States of America). We summarized these national RZV recommendations, focusing on herpes zoster vaccine preference, the age at which RZV is recommended, considerations before vaccination, vaccination schedule, the possibility of administering RZV together with other vaccines, vaccinating vulnerable populations and the safety of RZV. While national recommendations varied, most guidelines indicate that RZV is the preferred herpes zoster vaccine due to its high and persistent efficacy and as it can be administered to vulnerable populations who are at increased risk of herpes zoster and its complications. Recommendations have noted that side effects are common with RZV, however, most are of mild-moderate intensity and temporary (see also Figure 1).

Public Health Impact and Cost-Effectiveness of Non-live Adjuvanted Recombinant Zoster Vaccine in Canadian Adults.

OBJECTIVES: In Canada, incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN) are increasing, posing a significant burden on the healthcare system. This study aimed to determine the public health impact and cost effectiveness of an adjuvanted recombinant zoster vaccine (RZV) compared to no vaccination and to the live attenuated vaccine (ZVL) in Canadians aged 60 years and older. METHODS: A multi-cohort Markov model has been adapted to the Canadian context using recent demographic and epidemiologic data. Simulations consisted of age-cohorts annually transitioning between health states. Health outcomes and costs were discounted at 1.5% per year. The perspective of the Canadian healthcare payer was adopted. A coverage of 80% for the first RZV and ZVL dose and a compliance of 75% for the second RZV dose were assumed. RESULTS: RZV was estimated to be cost effective compared with no vaccination with an incremental cost-effectiveness ratio (ICER) of $28,360 (Canadian dollars) per quality-adjusted life-year (QALY) in persons aged ≥ 60 years, avoiding 554,504 HZ and 166,196 PHN cases. Compared with ZVL, RZV accrued more QALYs through the remaining lifetime and an increase in costs of approximately $50 million resulting in an average ICER of $2396. Results were robust under deterministic and probabilistic sensitivity analyses. HZ incidence rate and persistence of vaccine efficacy had the largest impact on cost effectiveness. CONCLUSIONS: The cost-utility analysis suggested that RZV would be cost effective in the Canadian population compared with no vaccination and vaccination with ZVL at a willingness-to-pay threshold of $50,000.

More than 95% of adults aged 50 are infected with varicella-zoster virus and are at risk of developing herpes zoster, also known as shingles. This risk is higher in older people and in people with a reduced immune system. Shingles causes a painful rash and may trigger persistent pain and other complications that greatly reduce quality of life. In Canada, Zostavax is the only existing approved vaccine against shingles. It has been offered in a publicly funded program in Ontario to those aged 65­70 years since September 2016. Shingrix, is a new shingles vaccine that has recently been approved by Health Canada for adults aged ≥ 50 years. The present model suggests that Shingrix confers higher protection against shingles compared to Zostavax, with a greater reduction in shingles episodes. The increase in vaccination costs would be partially offset by reduced healthcare visit and medication expenses. For these reasons, provincial health plans may consider offering Shingrix to people aged ≥ 50 years.

The comparative efficacy and safety of herpes zoster vaccines: A network meta-analysis.

BACKGROUND: We estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials. METHODS: A systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age. RESULTS: RZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VERZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VEZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VERZV = 0.91 (95%CI: 0.87, 0.94), VEZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VERZV = 0.89 (95%CI: 0.70, 0.96), VEZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VERZV = 0.89 (95%CI: 0.69, 0.96), VEZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs. CONCLUSION: RZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL.

Transcriptional inhibition of interleukin-12 promoter activity in Leishmania spp.-infected macrophages.

To establish and persist within a host, Leishmania spp. parasites delay the onset of cell-mediated immunity by suppressing interleukin-12 (IL-12) production from host macrophages. Although it is established that Leishmania spp.-infected macrophages have impaired IL-12 production, the mechanisms that account for this suppression remain to be completely elucidated. Using a luciferase reporter assay assessing IL-12 transcription, we report here that Leishmania major, Leishmania donovani, and Leishmania chagasi inhibit IL-12 transcription in response to interferon-gamma, lipopolysaccharide, and CD40 ligand and that Leishmania spp. lipophosphoglycan, phosphoglycans, and major surface protein are not necessary for inhibition. In addition, all the Leishmania spp. strains and life-cycle stages tested inhibited IL-12 promoter activity. Our data further reveal that autocrine-acting host factors play no role in the inhibitory response and that phagocytosis signaling is necessary for inhibition of IL-12.