Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and Varicella Zoster Virus Infection - Frequency of an Association.

To determine whether there is a correlation between myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases and varicella zoster virus (VZV) infection. We provide a case report and performed a study to determine the frequency of MOG antibodies (MOG-IgG) in neurological VZV infections. Patients admitted to the Medical University of Innsbruck from 2008-2020 with a diagnosis of a neurological manifestation of VZV infection (n=59) were included in this study; patients with neuroborreliosis (n=34) served as control group. MOG-IgG was detected using live cell-based assays. In addition, we performed a literature review focusing on MOG and aquaporin-4 (AQP4) antibodies and their association with VZV infection. Our case presented with VZV-associated longitudinally extensive transverse myelitis and had MOG-IgG at a titer of 1:1280. In the study, we did not detect MOG-IgG in any other patient neither in the VZV group (including 15 with VZV encephalitis/myelitis) nor in the neuroborreliosis group. In the review of the literature, 3 cases with MOG-IgG and additional 9 cases with AQP4 IgG associated disorders in association with a VZV infection were identified. MOG-IgG are rarely detected in patients with VZV infections associated with neurological diseases.

Primary varicella-zoster virus infection of the immunocompromised associated with acute pancreatitis and hemophagocytic lymphohistiocytosis: A case report.

RATIONALE: Primary varicella-zoster virus (VZV) infection may be associated with hemophagocytic lymphohistiocytosis (HLH), as well as with acute pancreatitis. However, there is few data concerning the evolution and the optimal treatment of these rare associations. PATIENT CONCERNS: A 57-year-old immunocompromised woman, who was treated for chronic lymphocytic leukemia 3 years prior to admission, was hospitalized with abdominal pain revealing severe acute pancreatitis. The day after admission, a pruritic rash appeared on her face, trunk, and limbs, sparing the palmoplantar regions. At the same time, fever, thrombocytopenia (27 × 109/L), major hyperferritinemia (11,063 µg/mL), hypertriglyceridemia (2.56 mmol/L) and elevated lactate dehydrogenase levels (1441 IU/L) suggested HLH. DIAGNOSIS: The diagnosis of chickenpox (varicella) was established. Primary VZV infection was then confirmed: cutaneous and plasma VZV polymerase chain reactions were positives, VZV serology was negative for IgG. INTERVENTIONS: Treatment with aciclovir was started intravenously after the onset of the rash, for a total of 10 days. A 48-h surveillance in intensive care was carried out. OUTCOMES: Acute pancreatitis and biological abnormalities evolved favorably under aciclovir. Platelet count was normalized 6 days after admission to hospital. LESSONS: A favorable outcome of primary VZV infection associated with severe acute pancreatitis and probable HLH in an immunocompromised patient is possible with aciclovir alone.

The frequency of interleukin-1ß-producing monocytes is significantly associated with varicella-zoster responses of nursing home residents.

Previous studies have demonstrated that the status of the T cell compartment and inflammation-related factors are associated with the immunogenicity of the varicella-zoster virus (VZV) vaccine in older adults; however, little is known about the roles of other immune cell subsets known to influence the generation and maintenance of immunological memory. Responses to a live-attenuated VZV vaccine were studied in relation to peripheral blood mononuclear cell (PBMC) composition and function in a sample of 30 nursing home residents (aged 80-99 years). Interferon-gamma enzyme-linked immunospot (ELISPOT) was used to measure VZV responses at baseline and 6 weeks following vaccination, and associations were sought with the frequencies of monocytes and T, B and natural killer (NK) cells and the production and secretion of cytokines following their ex-vivo stimulation with different agents. While only the frequency of interleukin (IL)-6+ CD14+ monocytes was inversely associated with post-vaccination VZV response, amounts of IL-1ß, IL-10, IL-17A and tumour necrosis factor (TNF) secreted by PBMCs and the frequency of IL-1ß+ CD14+ monocytes was positively correlated with pre-vaccination VZV response. Furthermore, both bivariate correlation and causal mediation analyses supported the notion that IL-1ß+ CD14+ monocytes were significant mediators of the associations between IL-1ß and TNF secretion by PBMCs and pre-vaccination VZV responses. Our findings implicate a strong cytokine response mediated by inflammatory IL-1ß+ monocytes in coordinating responses of long-lived VZV-reactive memory T cells, but with an opposing effect of IL-6+ CD14+ monocytes. Whether monocyte status promotes or inhibits the induction and/or maintenance of these memory T cells later in life has yet to be determined.

Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients.

BACKGROUND: Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection. METHODS: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines. RESULTS: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes. CONCLUSIONS: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.

Varicella zoster immunity loss in multiple sclerosis patient treated with ocrelizumab.

Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.

Varicella-zoster virus: molecular controls of cell fusion-dependent pathogenesis.

Varicella-zoster virus (VZV) is the causative agent of chicken pox (varicella) and shingles (zoster). Although considered benign diseases, both varicella and zoster can cause complications. Zoster is painful and can lead to post herpetic neuralgia. VZV has also been linked to stroke, related to giant cell arteritis in some cases. Vaccines are available but the attenuated vaccine is not recommended in immunocompromised individuals and the efficacy of the glycoprotein E (gE) based subunit vaccine has not been evaluated for the prevention of varicella. A hallmark of VZV pathology is the formation of multinucleated cells termed polykaryocytes in skin lesions. This cell-cell fusion (abbreviated as cell fusion) is mediated by the VZV glycoproteins gB, gH and gL, which constitute the fusion complex of VZV, also needed for virion entry. Expression of gB, gH and gL during VZV infection and trafficking to the cell surface enables cell fusion. Recent evidence supports the concept that cellular processes are required for regulating cell fusion induced by gB/gH-gL. Mutations within the carboxyl domains of either gB or gH have profound effects on fusion regulation and dramatically restrict the ability of VZV to replicate in human skin. This loss of regulation modifies the transcriptome of VZV infected cells. Furthermore, cellular proteins have significant effects on the regulation of gB/gH-gL-mediated cell fusion and the replication of VZV, exemplified by the cellular phosphatase, calcineurin. This review provides the current state-of-the-art knowledge about the molecular controls of cell fusion-dependent pathogenesis caused by VZV.

Elevated serum substance P during simian varicella virus infection in rhesus macaques: implications for chronic inflammation and adverse cerebrovascular events.

Varicella and zoster, produced by varicella-zoster virus (VZV), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. Because substance P is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after VZV infection, we measured serum substance P in simian varicella virus-infected rhesus macaques. We found significantly increased and persistent serum substance P concentrations during varicella and zoster compared with pre-inoculation, supporting the hypothesis that VZV-induced increases in serum substance P may contribute to increased stroke risk associated with VZV infection.

Infection as a Stroke Risk Factor and Determinant of Outcome After Stroke.

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.

Acute myocarditis following varicella zoster infection in an immunocompetent adolescent: An uncommon complication. / Miocarditis aguda tras una infección por el virus de la varicela-zóster en un adolescente inmunocompetente: una complicación poco frecuente.

Myocarditis is a serious complication of varicella zoster virus infection. A 15 year-old boy was admitted to the Emergency Department for chest pain, tachycardia and hypotension. An electrocardiogram showed sinus tachyicardia. Cardiac biomarkers were elevated and echocardiography revealed left ventricular apical, inferolateral, septal hypokinesis, and mitral regurgitation. Varicella zoster virus serum immunoglobulin M antibody was positive. The patient was discharged without any sequelae.

La miocarditis es una complicación grave de la infección por el virus de la varicela-zóster. Un varón de 15 años ingresó a la sala de emergencias debido a dolor torácico, taquicardia e hipotensión. En el electrocardiograma se observó taquicardia sinusal. Los biomarcadores cardíacos estaban elevados. En el ecocardiograma se notó hipocinesia apical, septal, e inferolateral del ventrículo izquierdo e insuficiencia mitral. Los anticuerpos IgM en suero para el virus de la varicela-zóster eran positivos. El paciente recibió el alta sin secuelas.

High varicella zoster virus susceptibility in Caribbean island populations: Implications for vaccination.

OBJECTIVES: Varicella zoster virus (VZV) infection is reported regularly among adolescents and adults in Caribbean island populations. The disease more often runs a severe course among these populations, causing a substantial burden. The aim of this sero-epidemiological study was to obtain an insight into VZV susceptibility and its determinants in island populations of the Caribbean Netherlands (CN). METHODS: Participants from Bonaire, St. Eustatius, and Saba (n = 1829, aged 0-90 years) donated a blood sample and completed a questionnaire. VZV-specific IgG antibodies were determined using a bead-based multiplex immunoassay. Risk factors were analysed using a logistic regression model. RESULTS: Overall seroprevalence in CN was 78%, being lowest on St. Eustatius (73%) and highest on Bonaire and Saba (79%). Seropositivity increased gradually with age, with 60% and 80% at ages 10 years and 30 years, respectively, and ranging between 80% and 90% thereafter. Higher odds for VZV seronegativity were seen among persons who were born in CN or had resided there since early childhood, and among single-person households. CONCLUSIONS: VZV susceptibility is relatively high among adolescents and adults in CN. In order to reduce the burden of VZV-related disease in these populations, routine varicella vaccination is recommended. As data are scarce, the study findings can serve as a blueprint for the epidemiology in tropical regions.

VZV-specific cell-mediated immunity, but not humoral immunity, correlates inversely with the incidence of herpes zoster and the severity of skin symptoms and zoster-associated pain: The SHEZ study.

Onset of herpes zoster (HZ) is thought to be related to a decline in cell-mediated immunity (CMI). However, until recently, there have been no large-scale prospective studies on the relationship between varicella-zoster virus (VZV)-specific CMI and the onset and severity of HZ. The Japanese researchers conducted a cohort study on VZV immunity in a population living on an island cluster, Shozu County in Japan, and examined the people who developed HZ during a follow-up period of three years to clarify the relationship between the onset and severity of HZ and immunity. In this study, they focused on the relationship between cell-mediated and humoral immunity and the onset and severity of HZ. CMI was measured by VZV skin test, and humoral immunity was assessed with serological tests for VZV-specific antibodies. A total of 12,522 people over the age of 50 were enrolled in this study, and 401 registrants were diagnosed as HZ. VZV-specific CMI assessed by VZV skin test showed a significant inverse relationship with the incidence of HZ and the severity of skin lesions and acute and subacute pain, and with the occurrence of postherpetic neuralgia. In contrast, VZV-specific antibody titer was not associated with the incidence and severity of HZ. These results suggest that VZV-specific CMI, but not humoral immunity, plays a key role in controlling the onset of HZ, the severity of skin lesions, and zoster-associated pain.

Immunity to Vaccine-preventable Viral Infections in Australians Being Evaluated for Liver Transplantation.

BACKGROUND: Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in immunocompromised patients. Current guidelines recommend routine screening and vaccination of all patients before solid organ transplantation. We studied rates of immunity against vaccine-preventable viruses in liver transplantation (LT) recipients. METHODS: We retrospectively studied consecutive adult patients who underwent first deceased donor LT at a single center between August 2008 and October 2017. Viruses studied were hepatitis A (HAV), hepatitis B (HBV), varicella zoster virus (VZV), measles, and mumps. Hepatitis B surface antibody (anti-HBs) <10 IU/mL in HBV surface antigen-negative patients and negative IgG to other viruses was regarded as absent immunity. RESULTS: Five hundred and fifty-five patients underwent LT (72.4% male; median age, 55.0 y). Percentages of patients who lacked immunity to vaccine-preventable infections were HAV (31.8%), HBV (63.8%), measles (1.4%), mumps (6.6%), and VZV (3.8%). Age was positively associated with immunity (from either past exposure or vaccination) against most viruses, including HAV, measles, mumps, and VZV (P < 0.05 for all). In contrast, older age was marginally associated with anti-HBs <10 IU/mL (P = 0.046). No significant changes in immunity rates were observed during the study period. CONCLUSIONS: A substantial number of patients undergoing LT are not immune to vaccine-preventable viruses at the time of assessment. This presents an opportunity for pre-LT vaccination and in particular younger patients may need to be targeted.

Seroprevalence and molecular characteristics of varicella-zoster virus infection in Chinese children.

BACKGROUND: Varicella-zoster virus (VZV) infection in children is an important public health problem in China. We performed the current study to explore the seroprevalence of VZV infection in Chinese children in order to provide more information for improvement of varicella vaccination in China. METHODS: Three thousand fourteen children were recruited from Chinese kindergarten students aged from four to six years. Anti-VZV IgG and IgM were assayed using enzyme-linked immunosorbent assay. Both ORF22 and ORF62 of VZV were amplified, sequenced, and analyzed by nested PCR. RESULTS: Among 3014 children, 43.9% of boys and 46.3% of girls were vaccinated with varicella vaccine, respectively. The seroprevalence of anti-VZV IgG was 54.4% in the children with varicella vaccination, which was significantly higher than those in unvaccinated children (49.2%) (χ2 = 8.206, P = 0.004). Among of the vaccinated children, the detection rates of VZV IgG antibody increased with age, with 49.4, 50.9 and 58.9% in 4, 5 and 6-year groups, respectively (Trend χ2 = 17.202, P = 0.002). However, there was no difference in anti-VZV IgG detection rates among those unvaccinated children in different age groups (Trend χ2 = 8.681, P = 0.070). In addition, 13 boys and 13 girls were positive for anti-VZV IgM, respectively. Among of them, eight children (0.6%) have received varicella vaccination, which was similar to those in unvaccinated children (1.1%). However, only one ORF22 sequence was isolated from an unvaccinated 5-year boy. Compared to the reference VZV sequences, the nucleotide homology was estimated to be 99.7% with genotype J. CONCLUSIONS: Our study indicated that about half of Chinese children aged four to six years have a high risk of VZV infection. It should be helpful for the evaluation on the necessity of varicella immunization in China.