Varicella-zoster Virus Infection Research Articles

Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.

Maxillary Osteonecrosis Related with Herpes Zoster: A Case Report and Review of the Literature

Osteonecrosis of the jaw (ONJ) can occur through various mechanisms including radiation, medication, and viral infections such as herpes zoster. Although herpes zoster is a varicella-zoster virus infection that can affect the trigeminal nerve, it rarely causes oral complications. The author reports a rare case of herpes zoster-related ONJ, followed by a review of the relevant literature pertaining to herpes zoster-related oral complications, including ONJ. A 73-year-old woman presented with a scarred skin lesion on her left midface with an exposed alveolar bone of the left maxilla. Based on her medical records, she received a diagnosis and treatment for herpes zoster six months prior and experienced a few teeth loss in the left maxilla following a fall preceding the onset of herpes zoster. Sequestrectomy of the left maxilla was performed and ONJ was diagnosed. The operative site recovered favorably. Although unusual, several cases of localized extensive ONJ in herpes zoster-infected patients have been reported. This case illustrates the possibility of a rare occurrence of unilateral widespread osteonecrosis of the jaw (ONJ) even in the maxilla associated with herpes zoster. The exact mechanism has not been elucidated; nevertheless, surgeons should consider the possibility of oral and dental complications, including ONJ, related to a history of herpes zoster.

Management of systemic lupus erythematosus: a systematic literature review informing the 2023 update of the EULAR recommendations

ObjectivesTo analyse the new evidence (2018–2022) for the management of systemic lupus erythematosus (SLE) to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations.MethodsSystematic literature reviews were...

Association of the Reduced Levels of Monocyte Chemoattractant Protein-1 with Herpes Zoster in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors in a Single-Center Cohort.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. Serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ-inducible protein-10 (IP-10) were measured by ELISA. Among the 66 enrolled RA patients, 24 developed new-onset HZ. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21 pg/mL, interquartile range (IQR) 77.63-150.30 pg/mL versus 142.3 pg/mL, IQR 106.7-175.6 pg/mL, p < 0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8 ng/mL, IQR 21.0-38.2 ng/mL versus 10.5 ng/mL, IQR 9.9-15.0 ng/mL, p < 0.005). Our results suggest an association between reduced MCP-1 levels and HZ development in JAKi-treated RA patients. High-titer anti-IFN-γ autoantibodies may be related to severe HZ in these patients.

Serum/glucocorticoid-regulated kinase 1 contributes to the proliferation of varicella-zoster virus and induction of cyclin B1 expression.

In this study, we investigated the role of serum/glucocorticoid-regulated kinase 1 (SGK1) in varicella-zoster virus (VZV) replication. VZV DNA replication and plaque formation were inhibited by SGK1 knockout and treatment with an SGK1 inhibitor. Furthermore, SGK1 inhibition suppressed the increase in cyclin B1 expression induced by VZV infection. These results suggest that VZV infection induces SGK1 activation, which is required for efficient viral proliferation through the expression of cyclin B1. This is the first study to report that SGK1 is involved in the VZV life cycle.

Computational analysis of antiviral drugs using topological descriptors

Many health challenges are attributed to viral infections, which represent significant concerns in public health. Among these infections, diseases such as herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) infections have garnered attention due to their prevalence and impact on human health. There are specific antiviral medications available for the treatment of these viral infections. Drugs like Cidofovir, Valacyclovir, and Acyclovir are commonly prescribed. These antiviral drugs are known for their efficacy against herpesviruses and related viral infections, leveraging their ability to inhibit viral DNA polymerase. A molecular descriptor is a numerical value that correlates with specific physicochemical properties of a molecular graph. This article explores the calculation of distance-based topological descriptors, including the Trinajstic, Mostar, Szeged, and PI descriptors for the aforementioned antiviral drugs. These descriptors provide insights into these drugs’ structural and physicochemical characteristics, aiding in understanding their mechanism of action and the development of new therapeutic agents.

Variable Clinical Courses of Varicella Zoster Virus Infection-related or Vaccination-related Bone Marrow Failure.

We report 5 children with bone marrow failure (BMF) after primary varicella zoster virus (VZV) infection or VZV vaccination, highlighting the highly variable course. Two patients were treated with intravenous immunoglobulins; one had a slow hematologic recovery, and the other was rescued by allogeneic hematopoietic stem cell transplantation (HSCT). Of the 2 patients treated with immunosuppressive therapy with antithymocyte globulin and cyclosporine, one had a complete response, and the other was transplanted for nonresponse. One patient underwent a primary allograft. All patients are alive. This study demonstrated that VZV-associated BMF is a life-threatening disorder that often requires HSCT.

Construction of a pathological model of skin lesions in acute herpes zoster virus infection and its molecular mechanism.

Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.

Epidemiological Characteristics of Varicella in Anhui Province, China, 2012-2021: Surveillance Study.

Varicella is a mild, self-limited disease caused by varicella-zoster virus (VZV) infection. Recently, the disease burden of varicella has been gradually increasing in China; however, the epidemiological characteristics of varicella have not been reported for Anhui Province. The aim of this study was to analyze the epidemiology of varicella in Anhui from 2012 to 2021, which can provide a basis for the future study and formulation of varicella prevention and control policies in the province. Surveillance data were used to characterize the epidemiology of varicella in Anhui from 2012 to 2021 in terms of population, time, and space. Spatial autocorrelation of varicella was explored using the Moran index (Moran I). The Kulldorff space-time scan statistic was used to analyze the spatiotemporal aggregation of varicella. A total of 276,115 cases of varicella were reported from 2012 to 2021 in Anhui, with an average annual incidence of 44.8 per 100,000, and the highest incidence was 81.2 per 100,000 in 2019. The male-to-female ratio of cases was approximately 1.26, which has been gradually decreasing in recent years. The population aged 5-14 years comprised the high-incidence group, although the incidence in the population 30 years and older has gradually increased. Students accounted for the majority of cases, and the proportion of cases in both home-reared children (aged 0-7 years who are not sent to nurseries, daycare centers, or school) and kindergarten children (aged 3-6 years) has changed slightly in recent years. There were two peaks of varicella incidence annually, except for 2020, and the incidence was typically higher in the winter peak than in summer. The incidence of varicella in southern Anhui was higher than that in northern Anhui. The average annual incidence at the county level ranged from 6.61 to 152.14 per 100,000, and the varicella epidemics in 2018-2021 were relatively severe. The spatial and temporal distribution of varicella in Anhui was not random, with a positive spatial autocorrelation found at the county level (Moran I=0.412). There were 11 districts or counties with high-high clusters, mainly distributed in the south of Anhui, and 3 districts or counties with high-low or low-high clusters. Space-time scan analysis identified five possible clusters of areas, and the most likely cluster was distributed in the southeastern region of Anhui. This study comprehensively describes the epidemiology and changing trend of varicella in Anhui from 2012 to 2021. In the future, preventive and control measures should be strengthened for the key populations and regions of varicella.

Myalgia‐induced discovery of rhabdomyolysis complicating generalized varicella in an immunocompetent patient: Case report and review of the literature

Key clinical messageIn a rare occurrence, primary varicella infection led to rhabdomyolysis in a 24‐year‐old with no medical history. Presenting with rash, fever, and weakness, he developed diffuse myalgia at 72 h. Elevated muscle enzymes confirmed rhabdomyolysis secondary to varicella zoster virus (VZV) infection. Treatment with acyclovir and hydration resulted in significant improvement within a month.AbstractPrimary varicella infection is rarely complicated by rhabdomyolysis. In this study, we describe a case of rhabdomyolysis complicating a VZV infection in a black subject. The patient was a 24‐year‐old black African with no particular medical history and was immunocompetent. He presented with an acute onset of generalized rash, fever, and generalized weakness. Physical examination revealed vesicular lesions typical of chickenpox. Antipyretic treatment combined with acyclovir was instituted in hospital. At the 72nd hour, diffuse myalgia developed. Muscle enzyme tests revealed CPK elevated to 40 times the upper limit of normal, LDH elevated to 2 times the upper limit of normal, ASAT and ALAT elevated to 7 times the upper limit of normal, and 2.5 times the upper limit of normal, respectively. We accepted the diagnosis of rhabdomyolysis secondary to VZV infection. The patient was given saline hydration and showed clinical and biological improvement 1 month later. A patient presenting with muscular symptoms during a VZV infection should be considered for rhabdomyolysis.

Nanopore sequencing in distinguishing between wild-type and vaccine strains of Varicella-Zoster virus

BackgroundThe introduction of varicella vaccines into routine pediatric immunization programs has led to a considerable reduction in varicella incidence. However, there have been reports of varicella, herpes zoster, and meningitis caused by the vaccine strain of varicella-zoster virus (VZV), raising concerns. Establishing the relationship between the wild-type and vaccine strains in VZV infections among previously vaccinated individuals is crucial. Differences in the single nucleotide polymorphisms (SNPs) among vaccine strains can be utilized to identify the strain. In this study, we employed nanopore sequencing to identify VZV strains and analyzed clinical samples. MethodsWe retrospectively examined vesicle and cerebrospinal fluid samples from patients with VZV infections. One sample each of the wild-type and vaccine strains, previously identified using allelic discrimination real-time PCR and direct sequencing, served as controls. Ten samples with undetermined VZV strains were included. After DNA extraction, a long PCR targeting the VZV ORF62 region was executed. Nanopore sequencing identified SNPs, allowing discrimination between the vaccine and wild-type strains. ResultsNanopore sequencing confirmed SNPs at previously reported sites (105,705, 106,262, 107,136, and 107,252), aiding in distinguishing between wild-type and vaccine strains. Among the ten unknown samples, nine were characterized as wild strains and one as a vaccine strain. Even in samples with low VZV DNA levels, nanopore sequencing was effective in strain identification. ConclusionThis study validates that nanopore sequencing is a reliable method for differentiating between the wild-type and vaccine strains of VZV. Its ability to produce long-read sequences is remarkable, allowing simultaneous confirmation of known SNPs and the detection of new mutations. Nanopore sequencing can serve as a valuable tool for the swift and precise identification of wild-type and vaccine strains and has potential applications in future VZV surveillance.

Acute Retinal Necrosis Complicated by Serous Retinal Detachment Associated with Varicella-Zoster Virus Infection in an Immunocompetent Young Adult

Acute retinal necrosis syndrome (ARN syndrome) is a rare, rapidly progressive viral retinitis with a grim functional prognosis. We present a case of a 43-year-old immunocompetent woman who experienced unilateral acute retinal necrosis, with Varicella-Zoster Virus (VZV) infection as the etiology. A unilateral vesicular facial rash accompanied by rapidly declining visual acuity over 7 days prompted consultation. Intravenous antiviral treatment and panretinal photocoagulation laser (PPR) were initiated, followed by antiviral prophylaxis. The patient developed ophthalmic zona lesions, peripheral retinal ischemia, and unilateral macular serous retinal detachment (SRD). Treatment included valacyclovir, corticotherapy and PPR laser. Knowledge of this condition, diagnosed clinically, is crucial due to its rapid progression and severe complications. Early intervention appears to be a significant prognostic factor, emphasizing its therapeutic urgency.

The associations of herpes simplex virus and varicella zoster virus infection with dementia: a nationwide retrospective cohort study

BackgroundIn this study, the risk of dementia in patients with a history of herpes simplex virus (HSV) or varicella zoster virus (VZV) infection was evaluated.MethodsThis nationwide cohort study used data from the Korean National Health Insurance Service collected between 2006 and 2017. A total of 752,205 subjects ≥ 45 years of age not diagnosed with dementia until 2006 were included. A multivariate Cox regression model, adjusted for age, sex, and other comorbidities, was used to assess the hazard ratio (HR) for dementia based on VZV or HSV infection. The interaction effects of both viral infections were analysed. Viral infections are classified into four categories: eye, central nervous system (CNS), simple, and complicated. The hazard ratio (HR) of viral infection was analysed based on the type of dementia.ResultsIn multivariable analysis, both HSV and VZV infection were associated with an increased risk of dementia (HR = 1.38, 95% confidence interval, CI:1.33–1.43) and (HR = 1.41, 95% CI:1.37–1.46), respectively. Patients who experienced both HSV and VZV infections were also at an increased risk of dementia (HR = 1.57, 95% CI:1.50–1.63). The co-infection group showed the shortest time from viral infection to dementia diagnosis (4.09 ± 3.02 years). In the subgroup analysis, all types of HSV and VZV infections were associated with an increased risk of dementia compared to the non-infection group. The eye, CNS, and complicated VZV infections were associated with a significantly higher risk than simple VZV infections. There were no significant differences between the subtypes of HSV infection. Furthermore, HSV, VSV, and co-infection were associated with an increased risk of all dementia types, including Alzheimer’s disease (AD) and vascular dementia (VD).ConclusionsIndividual HSV and VZV infections were associated with an increased risk of all types of dementia, including AD and VD. Patients co-infected with HSV and VZV, VZV infection in the eye, CNS, or complicated type were more vulnerable to the development of dementia.

Oncolytic varicella-zoster virus engineered with ORF8 deletion and armed with drug-controllable interleukin-12

BackgroundThe varicella-zoster virus (VZV), belonging to the group of human α-herpesviruses, has yet to be developed as a platform for oncolytic virotherapy, despite indications from clinical case reports suggesting a...

Genetic causal association between varicella-zoster virus infection and psychiatric disorders: A 2-sample Mendelian randomization study

BackgroundPsychiatric disorders, such as schizophrenia (SCZ), major depressive (MDD), and bipolar disorder (BD) have a profound impact on millions of individuals worldwide. The critical step toward developing effective preventive and treatment strategies lies in comprehending the causal mechanisms behind these diseases and identifying modifiable risk factors associated with them. MethodsIn this study, we conducted a 2-sample Mendelian randomization analysis to explore the potential links between chickenpox(varicella-zoster virus infection) and three major psychiatric disorders(SCZ, MDD, BD). ResultsIn our MR study, among the three major psychiatric disorders, chickenpox was shown to be causally related to BD, indicating that infection with chickenpox may increase the risk of developing BD (IVW: OR = 1.064, 95% CI =1.025–1.104, P=0.001; RAPS: OR=1.066, 95% CI=1.024–1.110, P=0.002), while there was no causal relationship between SCZ and MDD. Similar estimated causal effects were observed consistently across the various MR models. The robustness of the identified causal relationship between chickenpox and BD holds true regardless of the statistical methods employed, as confirmed by extensive sensitivity analyses that address violations in model assumptions. The MR–Egger regression test failed to reveal any signs of directional pleiotropy (intercept = −0.042, standard error (SE) = 0.029, p = 0.236). Similarly, the MR-PRESSO analysis revealed no evidence of directional pleiotropy or outliers among the chickenpox-related instrumental variables (global test p = 0.653). Furthermore, a leave-one-out sensitivity analysis yielded consistent results, further underscoring the credibility and stability of the causal relationship. ConclusionsOur findings provide compelling evidence of a causal effect of chickenpox on the risk of BD. To gain a more comprehensive understanding of this association and its underlying mechanisms, additional research is needed. Such investigations are pivotal in identifying effective interventions for promoting BD prevention.

VARICELLA-ZOSTER VIRUS INFECTION IN A PATIENT 12 DAYS POST RITUXIMAB: UNUSUAL CO-PRESENTATION OF SHINGLES AND CHICKENPOX

Rituximab, an anti CD20 monoclonal antibody, is used in the management of lymphoproliferative and autoimmune conditions such as pemphigus. As an immunosuppressor, it exposes patients to an increased risk of infection. Two cases of varicella-zoster virus infection post Rituximab were been reported in literature. The coexistence of chickenpox (primary infection) and shingles (reactivation of latent infection) in the same patient has never been reported in the literature, especially after rituximab treatment. Herein we present the first case of association of these 2 manifestations in a patient 12 days after rituximab therapy for pemphigus.

Vasculitis-like herpes zoster in the course of treatment with tofacitinib in ulcerative colitis: An assessment of local viral distribution by RNA insitu hybridization.

A 67-year-old man had taken the janus kinase (JAK) inhibitor, tofacitinib, for ulcerative colitis. He was referred to our department for a refractory ulcer on his lower leg. We suspected vasculitis and performed skin biopsy. Histopathological examination showed multinucleated giant cells in the epidermis and fibrinoid degeneration of small vessels in the upper dermis. Varicella zoster virus (VZV) DNA was detected by polymerase chain reaction and we diagnosed the patient with atypical vasculitis-like herpes zoster. The patient was treated with oral valacyclovir, but the rash persisted and took 2 months to heal. Immunostaining using anti-VZV antibody was positive mainly in epidermal keratinocytes, but was also observed to be positive in cells in the dermis. We further performed RNA insitu hybridization using a VZV ORF9 mRNA probe and clearly showed that the distribution of VZV mRNA extended into the dermis, including the dermal vessel walls and the eccrine sweat glands as well as the epidermis. The internal administration of JAK inhibitors may induce regional widespread VZV infection including vessels and involved in the formation of prolonged vasculitis-like manifestation. RNA insitu hybridization can be a potent tool for detecting the spread of VZV infection in the skin.

HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.

Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of postherpetic neuralgia (PHN). The immune escape mechanism of VZV remains to be elusive. Due to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well-established PHN mice model. Transcriptional expression analysis identified that the protein arginine methyltransferases 6 (Prmt6) was upregulated upon HSV-1 infection, which was further confirmed by immunofluorescence staining in spinal dorsal horn. Prmt6 deficiency decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load in vivo and in vitro. Overexpression of Prmt6 in microglia dampened antiviral innate immunity and increased HSV-1 load. Mechanistically, Prmt6 methylated and inactivated STING, resulting in reduced phosphorylation of TANK binding kinase-1 (TBK1) and interferon regulatory factor 3 (IRF3), diminished production of type I interferon (IFN-I) and antiviral innate immunity. Furthermore, intrathecal or intraperitoneal administration of the Prmt6 inhibitor EPZ020411 decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load. Our findings revealed that HSV-1 escapes antiviral innate immunity and results in PHN by upregulating Prmt6 expression and inhibiting cGAS-STING pathway, providing novel insights and a potential therapeutic target for PHN.

Abstract TMP8: Varicella Zoster Virus Infection in Children With Arterial Ischemic Stroke: The Chicken or the Egg?

Introduction: Serologic evidence of varicella zoster virus (VZV) infection has been associated with childhood arterial ischemic stroke (AIS). Questions of causality persist: does VZV infection cause AIS, or does AIS reactivate VZV? The Vascular effects of Infection in Pediatric Stroke (VIPS II) study aimed to examine this relationship. Methods: This North American 22-center prospective cohort study enrolled 205 children (28 days-18 years) with AIS (2017-2022). Blood samples were hyperacute (≤72hrs; n=194), acute (4-7 days; n=180) and convalescent (1-6 weeks; n=73). A virology research lab used ELISA to measure VZV IgM and IgG titers. A pediatric virologist (CG) interpreted the results and classified the evidence of infection. Low-level IgG seropositivity is consistent with prior vaccination/infection. Highly elevated IgM in hyperacute/acute samples indicated reactivation coincident with stroke . Rising IgG titers between hyperacute and convalescent samples, occasionally with a high IgM in convalescent sample, indicated reactivation after the stroke . Results: Median age (IQR) was 11.6 years (5.3, 15.6). All 205 cases were low-level IgG positive; 160 (78%) reported prior VZV vaccination and 3 reported remote chicken pox. Serologies for 15 (7.3%; 95% CI 4.1, 11.8%) indicated VZV reactivation coincident with stroke; prior VZV vaccination reported in 14 and unknown in one. Stroke etiology amongst these 15 was definite arteriopathy in 4 (27%), possible arteriopathy in 4 (27%), cardioembolic in 5 (33%), and idiopathic in 2 (13%) (compared to 37%, 37%, 10%, 14%, respectively, for the other 190). Among 73 with convalescent samples, 17 (23%) had VZV reactivation after stroke. All cases of VZV reactivation were asymptomatic zoster sine herpete (herpes zoster without rash). Conclusions: While stroke triggered VZV reactivation in 23% of cases, 7.3% had evidence of zoster sine herpete at the time of their stroke, implying a causal role. We could not distinguish antibodies to vaccine virus versus wild-type; these zoster cases could represent reactivation of vaccine virus or a break-through wild-type varicella infection. Either scenario would be unexpected in this current era of routine childhood VZV vaccination and low rates of pediatric chicken pox or zoster.

Effect of varicella‐zoster virus infection and antiviral treatment on the risk for dementia: A meta‐analysis of observational studies

AbstractBackground and purpose:There is increasing evidence to support a role for human herpes viruses in the development of neurodegenerative disorders; however, the association between varicella‐zoster virus (VZV) infection and dementia, and the effect of antiviral therapy on the risk for dementia remain unclear.MethodsWe searched PubMed, Embase, and the Cochrane Library databases from their dates of inception to May 2023. Odds ratios (ORs) with 95% confidence intervals (CIs) served as indicators of effect sizes in evaluations of the effect of VZV infection and antiviral treatment on dementia risk. Subgroup analyses based on study design, study location, diagnostic criteria of dementia, and VZV subtype classification were also performed.ResultsA total of 10 studies with 316,846 dementia cases were included in the meta‐analysis. We found that any VZV infection (OR: 1.04, 95% CI: .97–1.12; p = .22), herpes zoster (HZ) (OR: 1.05, 95% CI: .96–1.13; p = .28), or HZ involving the cranial nerves (OR: 1.36, 95% CI: .76–2.43; p = .304) was not associated with an increased risk of dementia. The results of subgroup analyses were consistent with these findings. However, patients infected with VZV who received antiviral treatment had a lower OR than untreated patients infected with VZV. Compared to individuals not infected with VZV, antiviral therapy in those infected with VZV was associated with reduced risk for dementia.ConclusionThe association between VZV infection and dementia may be masked by antiviral treatment. Further studies with longer follow‐up times that consider the severity of VZV infection and antiviral treatment are needed to clarify the contribution of VZV infection to the risk for dementia.