Varicella Zoster Virus Vasculopathy: An Under-Recognized Entity.

Varicella zoster virus (VZV) vasculopathy is a rare yet potentially severe neurological manifestation resulting from VZV reactivation, primarily affecting immunocompromised individuals. We present a case report of a 61-year-old male with VZV vasculopathy who initially presented with herpes zoster ophthalmicus, subsequently complicated by meningoencephalitis and an acute infarct in the territory of the left middle cerebral artery (MCA). Imaging revealed acute and chronic infarcts in the capsuloganglionic regions, accompanied by thickening and enhancement of the left MCA wall. Treatment involved a 14-day course of intravenous acyclovir, supplemented with oral prednisolone, resulting in modest clinical improvement. VZV vasculopathy represents an infrequently acknowledged neurological syndrome, particularly prevalent among immunocompromised individuals. Early recognition and appropriate intervention offer promise in ameliorating outcomes for affected patients. This case emphasizes the importance of including VZV vasculopathy in the differential diagnosis of neurological deficits, especially within high-risk populations.

New Insights Into the Therapeutic Management of Varicella Zoster Virus Meningitis: A Series of 123 Polymerase Chain Reaction-Confirmed Cases.

Background: Varicella zoster virus (VZV) can reactivate and cause meningitis, but few studies have distinguished it from meningoencephalitis regarding treatment recommendations.The objective of this study was to assess the outcomes of a large series of patients with VZV meningitis according to their therapeutic management. Methods: We conducted a bicentric retrospective cohort study, in Paris, France, including all adult patients with a cerebrospinal fluid sample positive for VZV by polymerase chain reaction between April 2014 and June 2022. We distinguished meningitis from encephalitis according to the International Encephalitis Consortium criteria. Unfavorable outcome was defined as mortality or functional sequelae defined by a loss of 2 points on the modified Rankin Scale. Results: We included 123 patients with meningitis. Among them, 14% received no antivirals, while 20% were treated with oral valacyclovir alone, 41% with a short course of intravenous (IV) acyclovir before switch to valacyclovir, and 25% with a long course of IV acyclovir. Outcomes were favorable regardless of antiviral regimen. In multivariate analysis, only age, underlying immunosuppression, and cranial radiculitis appear to be predictive factors for longer IV therapy, based on the Akaike information criterion. Conclusions: In this study, patients with VZV meningitis had a good outcome, with no evidence of any impact of the treatment strategy. However, further studies are needed to support the possibility of milder treatment in immunocompetent patients, avoiding cost and side effects of IV acyclovir.

Herpes Zoster Infection of Orofacial Region in a Geriatric Patient: A Case Report.

The varicella-zoster virus reactivates to cause the "herpes zoster" (HZ). ''Varicella-zoster virus'' (VZV) termed as ''HHV-3'' or ''human herpesvirus-3'' infection causes herpes zoster. Varicella, the primary form of the virus, is chickenpox, and the secondary form of the virus is herpes zoster also called shingles. During prior chicken pox episodes, this virus enters the body through cutaneous nerve endings and becomes dormant in the dorsal root ganglia. It sometimes affects the orofacial region and appears as unilaterally distributed burning pain, multiple, painful vesicular lesions, and ulcerations. Immunocompromised people are more likely to have disseminated zoster, which is defined as the involvement of three or more dermatomes. These are most likely to occur in elderly, immunocompromised patients, patients undergoing cancer chemotherapy, patients on immunosuppressants, and patients suffering from AIDS. This is a study of a male geriatric patient, aged 74 years, who reported unilateral pain, swelling, as well as multiple ulcerations on the left side of his face, extraorally as well as intraorally. The case was diagnosed as a herpes zoster infection involving V1 and V2 dermatome of the trigeminal nerve.

Majocchi Granuloma Superinfected With Herpes Zoster.

Herpes zoster (HZ) infection is caused by the reactivation of the varicella-zoster virus (VZV) and has very rarely been reported at the site of a superficial fungal infection. Also, HZ occurring at the site of a deep fungal infection has not been reported in the literature. We discuss a unique case of a 45-year-old male patient presenting with a Majocchi granuloma (MG) superinfected with disseminated HZ.

A Single-Center Case Series of Acute Retinal Necrosis at Teikyo University: Clinical Characteristics and Treatment Outcomes.

Aim To evaluate the clinical characteristics, treatment course, and prognosis of patients with acute retinal necrosis (ARN), which can rapidly progress and cause severe vision loss. Design Single-center retrospective case series. Subjects and methods Six patients and seven eyes diagnosed with ARN at Teikyo University Hospital were included in this study. The clinical presentation and treatment prognosis were investigated based on data obtained from medical records. Results The mean age of the patients at the initial diagnosis was 63.6 years. Although the mean Logarithm of the Minimum Angle of Resolution (LogMAR) visual acuity tended to decrease from 0.77 at the first visit to 1.29 at the last visit, the difference was not statistically significant. Intraocular manifestations observed during the study period included ocular hypertension (14.3%), anterior uveitis (100.0%), retinal hemorrhage (71.4%), vitreous opacity (100.0%), retinal exudative vasculitis (85.7%), optic nerve atrophy (85.7%), retinal vascular occlusion (85.7%), choroidal atrophy (85.7%), macular edema (100.0%), subretinal fluid in the macula (71.4%), and retinal detachment (85.7%). Treatment modalities included oral and intravitreal antivirals (85.7%), antiplatelet medications (85.7%), steroid eye drops (85.7%), subcapsular (57.1%) and vitreous (42.9%) steroid injections, oral steroids (71.4%), and surgical intervention (85.7%). Vitrectomy led to retinal recovery in all five eyes that underwent the procedure. Conclusions The visual prognosis of patients with ARN is poor, particularly in those with preexisting visual impairment. Early detection coupled with antiviral therapy and prompt surgical intervention have been identified as potential factors that influence visual outcomes. Given the severity of ARN, collecting data from multiple centers could aid in devising future diagnostic and therapeutic strategies.

Neurexin 3 Regulates Synaptic Connections Between Central Amygdala Neurons and Excitable Cells of the Lateral Parabrachial Nucleus in Rats with Varicella Zoster Induced Orofacial Pain.

Introduction: Herpes Zoster in humans is the result of varicella zoster virus (VZV) infection. Injecting rats with varicella zoster virus produces pain similar to herpes zoster "shingles" pain in humans. . In a previous study, orofacial pain was induced by injecting the whisker pad of male rats with VZV and the pain response increased after attenuating neurexin 3 (Nrxn3) expression in the central amygdala. Neurons descend from the central amygdala to the lateral parabrachial nucleus and orofacial pain signals ascend to the lateral parabrachial nucleus. GABAergic neurons within the central amygdala regulate pain by inhibiting activity within the lateral parabrachial nucleus. Attenuating Nrxn3 expression in the central amygdala increased GABA release in the lateral parabrachial nucleus suggesting Nrxn3 controls pain by regulating GABA release. Nrxn3 can also control synaptic connections between neurons, and we hypothesized that Nrxn3 knockdown in the central amygdala would reduce the number of GABAergic synaptic connections in the lateral parabrachial nucleus and increase VZV associated pain. Methods: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm. Results: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons. Discussion: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.

Seroprevalence of human herpes viruses in France, 2018-2022: a multilevel regression and poststratification approach.

BACKGROUND: Information related to herpes simplex virus 1 and 2 (HSV-1 and 2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) seroprevalence in France is either lacking, incomplete, or outdated, despite their public health burden. METHOD: We used routinely collected serological data between 2018 and 2022 to estimate HSV-1, HSV-2, VZV, EBV, and CMV seroprevalence in France. To account for demographic differences between our analytic samples and the French population and get estimates for sparsely sampled districts and age classes, we used a multilevel regression and poststratification approach combined with Bayesian model averaging via stacking weights. RESULTS: The observed seroprevalence (number of positive tests/number of tests) were 64.6% (93,294/144,424), 16.9% (24,316/144,159), 93.0% (141,419/152,084), 83.4% (63,199/75, 781), and 49.0% (23,276/47,525), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV. Between 2018 and 2022, France had a model-based average (equal-tailed interval at 95%) expected seroprevalence equal to 61.1% (60.7,61.5), 14.5% (14.2,14.81), 89.5% (89.3,89.8), 85.6% (85.2,86.0), and 50.5% (49.3,51.7), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV infections. We found an almost certain lower expected seroprevalence in Metropolitan France than in overseas territories for all viruses but VZV, for which it was almost certainly greater. The expected seroprevalences were likely greater among females for all viruses. LIMITATIONS: Our results relied on the assumption that individuals were sampled at random conditionally to variables used to build the poststratification table. IMPLICATIONS: The analysis highlights spatial and demographic patterns in seroprevalence that should be considered for designing tailored public health policies.

A unique case of double meningitis with enterovirus and reactivated varicella-zoster virus in a male teenager.

This paper presents a unique case of double meningitis with enterovirus and reactivated varicella-zoster virus without shingles in an immunocompetent male teenager, a case that offers many important medical lessons, all "gravitating" around physiopathological reasoning of any clinical case in general.

Assessment of the herpes zoster risk among renal transplant recipients administered the influenza vaccine.

BACKGROUND: Reactivation of the latent varicella-zoster virus can cause herpes zoster (HZ) infection, and renal transplant recipients undergoing immunosuppressive therapy are particularly susceptible to this condition. This study aims to evaluate the potential increase in HZ incidence following influenza vaccination among this specific patient population. METHODS: This study was a population-based, retrospective, self-controlled case series. Data were retrieved from Taiwan's National Health Insurance Research Database spanning the years 2008 to 2017. Patients diagnosed with HZ within a 6-month period before and after receiving the influenza vaccine were eligible for inclusion. Two distinct time intervals were defined for analysis: the initial 15 days and 30 days following vaccination were categorized as risk intervals, while all other periods served as control intervals. Incidence rate ratios (IRRs) were computed to compare HZ incidence during the risk intervals with that during the control intervals. RESULTS: This study encompassed a cohort of 4,222 renal transplant recipients who had received the influenza vaccine. Among this group, 67 recipients were subsequently diagnosed with HZ. The IRR during both the initial 15 days (IRR = 0.63; 95 % CI, 0.23-1.89) and the first 30 days (IRR = 1.50; 95 % CI, 0.71-3.16) following influenza vaccination did not demonstrate a statistically significant increase when compared to the post-exposure observation times. Comparable results were also observed when comparing these IRR values to the pre-exposure observation times. The subgroup analysis, stratified by age, sex, and underlying medical conditions (including cancer and autoimmune diseases), revealed that the IRRs did not exhibit statistically significant differences. CONCLUSIONS: No significant association between the influenza vaccine and an elevated risk of HZ was detected. The administration of annual influenza vaccines appears to be a reasonable practice for renal transplant recipients.

No Causal Effect of COVID-19 on Varicella-Zoster Infection, Herpes Zoster Progression, and Postherpetic Neuralgia: A Two-Sample Mendelian Randomization Study.

Purpose: Coronavirus disease (COVID-19) may trigger the reactivation of the latent varicella-zoster virus and may be a risk factor for herpes zoster (HZ). However, the causal relationship between COVID-19 and varicella-zoster infections remains controversial. This study aimed to estimate the causal inferences between COVID-19 and HZ. Methods: This study used a two-sample Mendelian randomization (MR) design. The inverse variance-weighted method was used as the primary method and sensitivity analyses were conducted, including the MR-Egger regression, weighted median and weighted mode. We searched at https://gwas.mrcieu.ac.uk/ using the keywords "COVID-19" for exposure data and "zoster" for outcome datasets. Results: We got 26 COVID-19 datasets and five zoster datasets. We used 26 COVID-19 datasets as exposure data corresponding to each zoster dataset for the MR analysis. There were nine datasets of COVID-19 where the number of SNPs was fewer than three in the MR analysis of the risk of HZ, varicella zoster virus (VZV) glycoprotein E and I antibody levels, anti-VZV IgG seropositivity, and post-zoster neuralgia. In addition, there were 10 datasets of COVID-19 where the number of SNPs was less than three in the MR analysis of anti-VZV IgG levels. The results of the MR analysis showed that all p-values were greater than 0.05. Sensitivity analysis revealed no evidence of horizontal pleiotropy in most two sample MR analyses. Conclusion: Our results indicate that there is no causal relationship between COVID-19 and varicella-zoster infection, HZ progression, and postherpetic neuralgia.

Transcriptional and functional remodeling of lung-resident T cells and macrophages by Simian varicella virus infection.

Introduction: Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in the sensory ganglia and disseminates to these sites remain unclear. Methods: We combined a single-cell sequencing approach and a well-established rhesus macaque experimental model using Simian varicella virus (SVV), which recapitulates the VZV infection in humans, to define the acute immune response to SVV in the lung as well as compare the transcriptome of infected and bystander lung-resident T cells and macrophages. Results and discussion: Our analysis showed a decrease in the frequency of alveolar macrophages concomitant with an increase in that of infiltrating macrophages expressing antiviral genes as well as proliferating T cells, effector CD8 T cells, and T cells expressing granzyme A (GZMA) shortly after infection. Moreover, infected T cells harbored higher numbers of viral transcripts compared to infected macrophages. Furthermore, genes associated with cellular metabolism (glycolysis and oxidative phosphorylation) showed differential expression in infected cells, suggesting adaptations to support viral replication. Overall, these data suggest that SVV infection remodels the transcriptome of bystander and infected lung-resident T cells and macrophages.

Herpes Zoster in a 13-Year-Old Male Without Prior Varicella Infection.

Herpes zoster (HZ) typically presents following reactivation of latent varicella-zoster virus (VZV) in adult and geriatric patients with a history of prior varicella infection. Primary VZV infection in patients compliant with vaccine schedules and without any immunocompromising condition is rare, with reactivation leading to HZ being even rarer. This case report details one such example involving a 13-year-old immunocompetent and fully immunized male with HZ despite no history of VZV infection, as well as possible explanatory mechanisms for this uncommon presentation. This case report contributes to a growing body of literature on atypical HZ presentations in pediatric populations without any history of prior VZV infection or exposure.

Varicella-Zoster Virus Reactivation After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation, Single-Center Experience of Acyclovir Prophylaxis.

BACKGROUND: Varicella-zoster virus (VZV) reactivation is the most common infectious complication in the late posthematopoietic stem cell transplantation (HSCT) period and is reported as 16%-41%. Acyclovir prophylaxis is recommended for at least 1 year after HSCT to prevent VZV infections. However, studies on the most appropriate prophylaxis are ongoing in pediatric patients. METHODS: Patients who underwent allogeneic HSCT between January 1, 1996 and January 1, 2020 were retrospectively analyzed to outline the characteristics of VZV reactivation after allogeneic HSCT in pediatric patients using 6 months acyclovir prophylaxis. RESULTS: There were 260 patients and 273 HSCTs. Median age was 10.43 (0.47-18.38), and 56% was male. Median follow-up was 2325 days (18-7579 days). VZV reactivation occurred in 21.2% (n = 58) at a median of 354 (55-3433) days post-HSCT. The peak incidence was 6-12 months post-HSCT (43.1%). Older age at HSCT, female gender, history of varicella infection, lack of varicella vaccination, low lymphocyte, CD4 count, and CD4/CD8 ratio at 9 and 12 months post-HSCT was found as a significant risk for herpes zoster (HZ) in univariate analysis, whereas history of varicella infection and low CD4/CD8 ratio at 12 months post-HSCT was an independent risk factor in multivariate analysis. CONCLUSIONS: Tailoring acyclovir prophylaxis according to pre-HCT varicella history, posttransplant CD4 T lymphocyte counts and functions, and ongoing immunosuppression may help to reduce HZ-related morbidity and mortality.

Cytomegalovirus, Epstein-Barr Virus, Herpes Simplex Virus, and Varicella Zoster Virus Infection Dynamics in People with Multiple Sclerosis from Northern Italy.

Previous exposure to Epstein-Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with MS in an Italian population. Serum samples (n = 200) from Italian people with multiple sclerosis (PwMS) classified as the relapsing-and-remitting clinical phenotype and (n = 137) healthy controls (HCs) were obtained from the CRESM Biobank, Orbassano, Italy. Both PwMS and HCs samples were selected according to age group (20-39 years, and 40 or more years) and sex. EBV virus capsid antigen (VCA) IgG, EBV nucleic acid-1 antigen (EBNA-1) IgG, CMV IgG, herpes simplex virus (HSV) IgG, and varicella zoster virus (VZV) IgG testing was undertaken using commercial ELISAs. EBV VCA IgG and EBNA-1 IgG seroprevalences were 100% in PwMS and 93.4% and 92.4%, respectively, in HCs. EBV VCA IgG and EBNA-1 IgG levels were higher (p < 0.001) in PwMS compared with HCs. For PwMS, the EBNA-1 IgG levels decreased with age, particularly in females. The CMV IgG seroprevalence was 58.7% in PwMS and 62.9% in HCs. CMV IgG seroprevalence increased with age. The HSV IgG seroprevalence was 71.2% in PwMS and 70.8% in HCs. HSV IgG levels were lower (p = 0.0005) in PwMS compared with HCs. VZV IgG seroprevalence was 97.5% in PwMS and 98.5% in HCs. In the population studied, several herpesvirus infections markers may have been influenced by the age and sex of the groups studied. The lack of a negative association of MS with CMV infection, and the observation of lower levels of HSV IgG in PwMS compared with HCs are findings worthy of further investigation.

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.

The Incidence of Herpes Zoster Complications: A Systematic Literature Review.

INTRODUCTION: The objective of this work was to summarize the incidence of herpes zoster (HZ) complications in different populations. METHODS: Systematic literature review of PubMed, Embase, and Virtual Health Library records between January 1, 2002 and October 20, 2022 using search strings for HZ, complications, and frequency measurements. RESULTS: The review included 124 studies, most conducted in the general population (n = 93) and on individuals with comorbidities (n = 41) ≥ 18 years of age. Most studies were conducted in Europe (n = 44), Asia (n = 40), and North America (n = 36). Postherpetic neuralgia (PHN) was the most studied neurological complication. Variable relative PHN incidence was found in the general population (2.6-46.7%) or based on diagnosis: immunocompromised (3.9-33.8%), depression (0-50%), and human immunodeficiency virus (HIV) (6.1-40.2%). High incidence rates were observed in hematological malignancies (HM) and solid organ malignancies (132.5 and 93.7 per 1000 person-years, respectively). Ocular complications were frequently reported with herpes zoster ophthalmicus (HZO). The relative incidence (incidence rate) of HZO in the general population was reported as 1.4-15.9% (0.31-0.35 per 1000 person-years). High relative incidence was observed in HIV (up to 10.1%) and HM (3.2-11.3%). Disseminated HZ was the most frequently reported cutaneous complication. The relative incidence of disseminated HZ was 0.3-8.2% in the general population, 0-0.5% in the immunocompetent, and 0-20.6% in patients with comorbidities. High relative incidence was reported in HM and solid organ transplant (up to 19.3% and 14.8%, respectively). DISCUSSION: Most reported complications were neurological (n = 110), ocular (n = 48), and cutaneous (n = 38). Few studies stratified complications by age or gender (or both). Incidence appeared higher in select immunocompromised populations. Higher incidence was associated with older age in several studies; the general association with gender was unclear. CONCLUSIONS: Variable incidence of HZ complications was reported by population subgroup. Further research is required to quantitatively analyze incidence by age, gender, and location.

Safety and Immunogenicity of the Live Attenuated Varicella Vaccine in Vietnamese Children Aged 12 Months to 12 Years: An Open-Label, Single-Arm Bridging Study.

OBJECTIVE: This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years. METHODS: This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42). RESULTS: All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed. CONCLUSION: The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella.

Silicon or Calcium Doping Coordinates the Immunostimulatory Effects of Aluminum Oxyhydroxide Nanoadjuvants in Prophylactic Vaccines.

Aluminum salts still remain as the most popular adjuvants in marketed human prophylactic vaccines due to their capability to trigger humoral immune responses with a good safety record. However, insufficient induction of cellular immune responses limits their further applications. In this study, we prepare a library of silicon (Si)- or calcium (Ca)-doped aluminum oxyhydroxide (AlOOH) nanoadjuvants. They exhibit well-controlled physicochemical properties, and the dopants are homogeneously distributed in nanoadjuvants. By using Hepatitis B surface antigen (HBsAg) as the model antigen, doped AlOOH nanoadjuvants mediate higher antigen uptake and promote lysosome escape of HBsAg through lysosomal rupture induced by the dissolution of the dopant in the lysosomes in bone marrow-derived dendritic cells (BMDCs). Additionally, doped nanoadjuvants trigger higher antigen accumulation and immune cell activation in draining lymph nodes. In HBsAg and varicella-zoster virus glycoprotein E (gE) vaccination models, doped nanoadjuvants induce high IgG titer, activations of CD4+ and CD8+ T cells, cytotoxic T lymphocytes, and generations of effector memory T cells. Doping of aluminum salt-based adjuvants with biological safety profiles and immunostimulating capability is a potential strategy to mediate robust humoral and cellular immunity. It potentiates the applications of engineered adjuvants in the development of vaccines with coordinated immune responses.

Varicella-Zoster Virus-Induced Neurologic Disease After COVID-19 Vaccination: A Multicenter Observational Cohort Study.

Background: Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus-induced neurologic disease (VZV-ND). Methods: This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid. Results: We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non-VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25-128) and 82 days (IQR, 36-132) for VZV-ND and non-VZV-ND, respectively, not reaching statistical significance (P = .056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P = .2). Conclusions: We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance.

Varicella-zoster virus-related neurological complications: From infection to immunomodulatory therapies.

The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.