VZV Reactivation Research Articles

NEURORETINITIS ASSOCIATED WITH COVID-19 INFECTION AND VARICELLA-ZOSTER VIRUS REACTIVATION.

To report a case of neuroretinitis as the presenting manifestation of COVID-19 infection alongside VZV reactivation, in the absence of other systemic symptoms. A case report. A previously healthy 15-year-old male presented with a one-week history of acute unilateral visual loss and clinical findings consistent with neuroretinitis. Diagnostic work-up revealed a positive nasopharyngeal swab PCR for COVID-19 and serology showed the presence of IgM and IgG antibodies for VZV. Following a comprehensive treatment regimen involving intravenous acyclovir, high-dose intravenous steroids and oral doxycycline, rapid and remarkable improvements were observed. The macular star and optic disc swelling regressed, and visual acuity improved from 20/200 to 20/20. This case offers valuable insights into the neuroretinitis associated with COVID-19 infection and VZV reactivation.

Safety of high efficacy therapies in older people with Multiple Sclerosis: A real-world evidence study

Introductionthe increase of older adults living with Multiple Sclerosis (MS) is associated with higher use of high efficacy therapies (HETs) in a clinical practice. The are no data regarding the safety of HET in this patient group. Objective: to analyze the safety of HETs in older people with MS (pwMS) in a real-life cohort. Methodsretrospective cohort study including pwMS under HETs (cladribine and monoclonal antibodies) treated in two specialized MS centers in Latin America. We compare: pwMS ≥ 50 years old (G1) and < 50 years old (G2). In all pwMS, presence and type of adverse events, and comorbidities were recorded. Results882 pwMS were included, 141 (15.9 %) had ≥50 years old, 47 (33.3 %) werunde HETs (G1). The most used DMT in G1 was ocrelizumab (48.9 %), mean time under HETs: 2.06 ± 0.8 years. The most frequent adverse event in G1 was urinary tract infection (UTI) (21.3 %). We did not find significant differences between G1 and G2 in infusion reactions, lymphopenia, neoplasms, respiratory infections, and liver disease. We found differences in the frequency of urinary tract infections (p = 0.004). No cases of VZV reactivation, tuberculosis or progressive multifocal leukoencephalopathy were registered. In a regression model adjusted for MS evolution, time under HET, EDSS, Charlson comorbidity index and phenotype, patients 50 ≥ under HETs did not have a higher incidence of adverse events compared to < 50 (Adjusted OR 0.72; CI95 % 0.143 -3.43, p = 0.67)} Conclusionthe short term use of HETs in pwMS older than 50 years old seems to be safe.

Herpes Zoster and Postherpetic Neuralgia

This research investigates the community health of Herpes Zoster (HZ) and the occurrence of postherpetic neuralgia (PHN) following VZV reactivation. The study adopts a practical approach, engaging rigid addition/forbiddance tests to outline the study culture. Diagnostic methods for HZ and PHN include severe dossier accumulation and accompanying moral concerns addressed. While accepting study restraints, this research investigates mathematical patterns of HZ occurrence and labels associations between the two points of HZ and the PHN incident.Descriptive enumerations disclose key understandings of HZ and PHN occurrence, peeling light on mathematical styles. The study stresses the dispassionate pertinence of allure judgments, interpreting results in the circumstances of existing biography. Mechanisms providing for PHN are surveyed, underscoring potential associations for dispassionate practice. Despite disadvantages, this research highlights the need for productive administration policies and deterrent measures.This study considerably contributes to understanding HZ and PHN, stressing their impact on community health and patient comfort. The verdicts offer valuable observations for clinicians and investigators alike, along with suggestions for future research directions. Through this research, an inclusive understanding of the community health of HZ and the incident of PHN is reached, providing a company for enhanced patient care and community health mediation.

RETRACTION: A predictive model of herpes zoster after allogeneic hematopoietic stem cell transplantation: VZV reactivation following antiviral prophylaxis discontinuation.

Retraction: Feng, C-J. , Zhao, P. , Fu, H-X. , Yan, C-H. , Wang, C-C. , Zhu, X-L. , He, Y. , Wang, F-R. , Zhang, Y-Y. , Mo, X-D. , Kong, Y. , Han, W. , Wang, J-Z. , Wang, Y. , Chen, H. , Chen, Y-H. , Zhao, X-Y. , Chang, Y-J. , Xu, L-P. , Liu, K-Y. , Huang, X-J. , Zhang, X-H. (2023) A predictive model of herpes zoster after allogeneic hematopoietic stem cell transplantation: VZV reactivation following antiviral prophylaxis discontinuation. American Journal of Hematology. https://doi.org/10.1002/ajh.27090. The above article, published online on 29 September 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief Carlo Brugnara and Wiley Periodicals LLC. The retraction has been agreed following notification by a third party who identified methodological errors in the published article. The journal conducted an investigation including post-publication review by an independent expert, who confirmed that the errors were substantial. The authors provided a point-for-point response to the journal about these concerns. However, the journal concluded that while some errors could be corrected, the methodology and data still would contain fundamental errors that invalidate the conclusions. The authors disagree with this retraction."

Computed tomography manifestations of a case of varicella zoster virus (VZV) pneumonia.

Disseminated VZV infections is rare in healthy adults. Several studies have reported VZV reactivation and eruption happens in an immunocompromised host especially after solid organ transplantation. Nonetheless, diffuse bilateral lung VZV infections is also rare. We report a case of disseminated VZV pneumonia after renal transplantation and methylprednisolone treatment. This report highlights the computed tomography manifestations of disseminated VZV pneumonia.

A-308 The Molecular Diagnosis of Varicella Zoster Virus (VZV): A Validation of a Real-Time PCR (qPCR) Assay for the Qualitative Detection

Abstract Background Varicella zoster virus (VZV) is the etiological agent of chicken pox and herpes zoster. After the primary infection, which usually occurs in childhood, VZV remains latent in sensory nerve roots for life. When reactivation occurs, especially in immunocompromised patients, the virus migrates to the skin and causes painful rashes that can evolute to a dermatome. Even after the end of the viral acute infection, some individuals may experience continued pain. Furthermore, VZV reactivation can lead to a wide spectrum of clinical manifestations such as self-limited radicular pain and central nervous system involvement. During acute illness, 90% of patients experience pain and 12% have symptoms similar to influenza infection (influenza-like). Immunocompromised patients may have an unfavorable course with disseminated infection, pneumonitis, hepatitis, and encephalitis. The cerebrospinal fluid polymerase chain reaction (PCR) test is indicated for suspected involvement of the central nervous system and complications of ocular or periocular lesions. Compared to other diagnostic methods, real-time PCR has great advantages as its high throughput, efficiency, and sensitivity. Therefore, the detection of VZV by real-time PCR presents great importance for the diagnosis and monitoring of the disease due to its precision and agility. Thus, we intended to validate a qualitative method for VZV detection by real-time PCR. Methods We evaluated the performance of the inventoried TaqMan assay (Vi06439647_s1) (Thermo Fisher Scientific). For this validation, we used 64 samples - whole blood (n = 31), cerebrospinal fluid (n = 32), vaginal lesion scraping (n = 1) - from the Genetics sector of the Pardini Group, previously tested by in-house PCR for the qualitative detection of VZV. Samples were extracted using the MagNA Pure 24 System platform (Roche Diagnostics) with the MagNA Pure 24 Total NA Isolation Kit, according to the manufacturer's instructions. All assays were performed using Taqman Universal Master Mix (Thermo Fisher Scientific). The inventoried B-actin Assay (assay ID: Hs01060665_g1) (Thermo Fisher Scientific) was used as endogenous control. Assay verification tests, evaluation of reaction efficiency, and determination of the detection limit (LOD) were performed using a synthetic control of known concentrations and a pool of negative samples (healthy volunteers). At the end of the tests, were made a comparison of the previous results with the results obtained in the ThermoFisher Real-Time PCR Assay. Results The Inventoriad Taqman Assay (VZV) had a limit of detection of 10 copies/µL and the Cq &amp;gt; 35 was defined as a cut-off to consider a sample as positive. Whole blood samples had higher Cts than cerebrospinal fluid samples, indicating lower viremia. Whitin all evaluated samples, 11 samples had positive results detected by in-house PCR (9 from whole blood and 2 from cerebrospinal fluid). Of these, 10 had a result detected in Real-time PCR and the agreement with the positive results between compared methodologies was 91.0%. The divergent sample was whole blood and can be related to DNA degradation. The 47 negative samples evaluated were concordant in both methods. Conclusion The inventoried TaqMan Assay with Taqman Universal Master Mix protocol evaluated was sensitive, fast, and applicable as a tool for the qualitative detection of VZV.

Vestibular Dysfunction Secondary to Reactivation of the Neurotropic Virus VZV After COVID-19: A Case Study.

BACKGROUND The novel coronavirus COVID-19 infection, caused by the SARS-CoV-2 virus, was declared a global pandemic by the World Health Organization (WHO) in March 2020. As of April 14, 2021, the virus has impacted the lives of over 138 million lives globally, with hundreds of thousands more impacted each day. COVID-19 has resulted in a multitude of clinical manifestations such as respiratory pathology, cardiovascular complications, and neurological dysfunction, and recent evidence points to potential changes in vestibular function secondary to COVID-19 infection. CASE REPORT We present the case of a 67-year-old female patient presenting with vertigo, hearing loss, tinnitus, aural dullness, dizziness, and imbalance following a diagnosis of shingles after contracting COVID-19. Results of a comprehensive balance evaluation were suggestive of a right peripheral vestibulopathy, otolith dysfunction, and a right-sided sensorineural hearing loss. The patient's subjective and objective data may support the claim that COVID-19 can lead to an increase in cases of vestibular dysfunction after reactivation of neurotropic viruses. CONCLUSIONS Our study and others suggest the possibility of vestibular deficits following the reactivation of VZV following a period of immunosuppression in conjunction with the lowered cell-mediated immunity caused by COVID-19. Additionally, vestibular interventions such as advanced vestibular treatment could be used to improve vestibular function in a linear manner.

Palmer Station, Antarctica: A ground-based spaceflight analog suitable for validation of biomedical countermeasures for deep space missions

Astronauts are known to exhibit a variety of immunological alterations during spaceflight including changes in leukocyte distribution and plasma cytokine concentrations, a reduction in T-cell function, and subclinical reactivation of latent herpesviruses. These alterations are most likely due to mission-associated stressors including circadian misalignment, microgravity, isolation, altered nutrition, and increased exposure to cosmic radiation. Some of these stressors may also occur in terrestrial situations. This study sought to determine if crewmembers performing winterover deployment at Palmer Station, Antarctica, displayed similar immune alterations. The larger goal was to validate a ground analog suitable for the evaluation of countermeasures designed to protect astronauts during future deep space missions. For this pilot study, plasma, saliva, hair, and health surveys were collected from Palmer Station, Antarctica, winterover participants at baseline, and at five winterover timepoints. Twenty-six subjects consented to participate over the course of two seasons. Initial sample processing was performed at Palmer, and eventually stabilized samples were returned to the Johnson Space Center for analysis. A white blood cell differential was performed (real time) using a fingerstick blood sample to determine alterations in basic leukocyte subsets throughout the winterover. Plasma and saliva samples were analyzed for 30 and 13 cytokines, respectively. Saliva was analyzed for cortisol concentration and three latent herpesviruses (DNA by qPCR), EBV, HSV1, and VZV. Voluntary surveys related to general health and adverse clinical events were distributed to participants. It is noteworthy that due to logistical constraints caused by COVID-19, the baseline samples for each season were collected in Punta Arenas, Chile, after long international travel and during isolation. Therefore, the Palmer pre-mission samples may not reflect a true normal ‘baseline’. Minimal alterations were observed in leukocyte distribution during winterover. The mean percentage of monocyte concentration elevated at one timepoint. Plasma G-CSF, IL1RA, MCP-1, MIP-1β, TNFα, and VEGF were decreased during at least one winterover timepoint, whereas RANTES was significantly increased. No statistically significant changes were observed in mean saliva cytokine concentrations. Salivary cortisol was substantially elevated throughout the entire winterover compared to baseline. Compared to shedding levels observed in healthy controls (23%), the percentage of participants who shed EBV was higher throughout all winterover timepoints (52–60%). Five subjects shed HSV1 during at least one timepoint throughout the season compared to no subjects shedding during pre-deployment. Finally, VZV reactivation, common in astronauts but exceptionally rare in ground-based stress analogs, was observed in one subject during pre-deployment and a different subject at WO2 and WO3. These pilot data, somewhat influenced by the COVID-19 pandemic, do suggest that participants at Palmer Station undergo immunological alterations similar to, but likely in reduced magnitude, as those observed in astronauts. We suggest that winterover at Palmer Station may be a suitable test analog for spaceflight biomedical countermeasures designed to mitigate clinical risks for deep space missions.

A Case of Haemorrhagic Herpes Zoster

Background: Varicella-zoster virus (HHV3) is one of the virus in herpes family. Herpes zoster results from the reactivation of varicella-zoster virus in the dorsal root ganglion. This reactivation occurs in immunocompromised conditions such as people with cancer, organ transplant recipients or those receiving chemotherapy, and people with HIV. Old age is also an important risk for the development of herpes zoster. Immunocompromised patients are at increased risk of VZV reactivation because of reduced T cell-mediated immunity. Emotional stress has also been mentioned as an associated factor in people with herpes zoster. The Classic clinical presentation consists of clear vesicular eruptions in dermatomal distribution which are painful. An immunocompromised individual may have frequent attacks of herpes zoster, cutaneous dissemination, organ involvement, and hemorrhagic herpes zoster. Haemorrhagic herpes zoster is an atypical form of herpes zoster develops in patients who are immunosuppressed and people of advanced age who are taking antiplatelets, and anticoagulants, and also in patients with thrombocytopenia due to any cause. The most common Association of herpes zoster is observed with lymphocytic leukemia and less frequently with myeloid leukemia. Management icludes antiviral therapy along with management of haemorrhagic conditions. Case Report: A nondiabetic male of 60 years attended the medicine outpatients department with complaints of epistaxis for two days. No history of bleeding from other sites was evident. There was no history of trauma or taking of anticoagulants or antiplatelets. No history of fever. The patient was anaemic and an erythematous rash was evident along the right T6 dermatome. He was admitted to the general medicine ward. On the second day of his admission, our patient developed painful haemorrhagic bullous lesions over the right T6 dermatome resembling a bunch of grapes and erythematous popular lesions all over his body (Figure 1). The bullous lesions became larger in size in the subsequent two days of admission. On query, he mentioned that he had suffered from Varicella Zoster in his early childhood. Patients haemoglobin was 10.70 gm/dl, total count of white blood cell (WBC) was 13.20 K/ mm3 (normal value 4.00 – 11.00 K/ mm3), neutrophil and lymphocyte counts were 2.38 K/ mm3 (normal value 2.16 – 6.04 K/ mm3) and 10.38 K/ mm3 (normal value 0.6 – 3.06 K/ mm3) respectively. His platelet count was 5.00 K/ mm3 (normal value 150.00 – 400.00 K/ mm3). The patient denied skin biopsy. A diagnosis of haemorrhagic herpes zoster was made after a dermatology consultation and oral valacyclovir was started along with oral and topical antibiotics and regular dressings. After six units of platelet transfusion patients, the platelet count was raised to 30 K/ mm3. Peripheral blood film was suggestive of acute leukaemia. A bone marrow examination was suggestive of acute myeloid leukaemia. The patient was transferred to the haemato-oncology ward for further planning and management. Conclusion: Haemorrhagic herpes zoster may occur in different clinical conditions and one of them although rare, is acute myeloid leukaemia. Clinical scenario along with bone marrow and blood picture helps to reach a diagnosis in such cases.

2158. Monitoring of Varicella specific T-cell mediated immunity in pediatric allogenic hematopoietic stem cell transplant recipients

Abstract Background Varicella-zoster virus (VZV) infection is known to occur in 13-55% of patients within the first year after hematopoietic stem cell transplant (HSCT). The dynamics of recovery of VZV-specific T cell- mediated immunity (CMI) and its role for prevention and control of VZV reactivation are rarely reported in pediatric allogenic HSCT recipients. Methods From April 2019 to February 2020, subjects aged younger than 19 years who underwent allogenic HSCT with at least 1 year of follow up at Asan Medical Center Children`s Hospital were prospectively enrolled. All of them underwent VZV-specific enzyme-linked immune absorbent spot (ELISPOT) assays just before HSCT and then at 1, 3 months following HSCT. Extension study, which measures VZV-specific CMI before and after VZV vaccination at 24 months post-HSCT, is currently underway. Results A total of 32 HSCT recipients with a median age of 11years were enrolled. 37.5% underwent haploidentical HSCT and VZV R+ were in 78.1%. Antiviral prophylaxis was applied to all HSCT recipients, of which 65.6% were applied up to 365 days after HSCT. During this study period, only 1 patient (3.1%) experienced herpes zoster at 23 months following HSCT, whose VZV-specific ELISPOT assay showed 0, 1, and 0 spot-forming cells (SFC)/2.0x105 cells before HSCT, 1 and 3 months following HSCT, respectively. The presence of VZV-specific CMI ≥ 1 SFC/ 2.0 × 105 cells was observed in 62.5 % before HSCT, 65.6 % at 1 month, 59.4 % at 3 months, and 70% at 24 months after HSCT, respectively. However, only 18.8 % ,12.5 % and 21.9 % recovered VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cells at 1, 3 and 24 months following HSCT. Meanwhile, all the 4 recipients who got the 1st VZV vaccination at 24 months following HSCT showed recovery of VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cell. Recovery of VZV-specific CMI after HSCT was not associated with VZV serostatus, chickenpox history, type of HSCT, conditioning regimens, and GVHD. Conclusion Only a few pediatric allogenic HSCT recipients recovered VZV-specific CMI with ≥ 5 SFC/ 2.0 × 105 cell up to 2 years following HSCT. In addition, the association between VZV-specific CMI and VZV reactivation could not be analyzed because no one experienced VZV reactivation within 1 year after HSCT. More long-term large-scale multicenter study is mandatory to supplement these parts. Disclosures All Authors: No reported disclosures.

Recurrent facial palsy: Characteristics of ipsilateral and alternative palsies of 104 cases

ObjectiveRecurrent facial palsy is relatively rare and its clinical details of recurrent facial palsy are not well known. We analyzed recurrent facial palsy cases and clarified its characteristics, especially the difference between ipsilateral and alternative palsies. The analysis aimed to obtain information about recurrent facial palsy that would be useful for delivering explanations to patients and help improve recurrent facial palsy treatments based on the etiology. MethodsWe picked up data from the chart and analyzed the clinical characteristics of patients with recurrent facial palsy from 1243 facial palsy patients (Bell's palsy, VZV-related palsy (Ramsay Hunt syndrome and zoster sine herpete [ZSH])) between 2006 and 2020. ResultsRecurrent facial palsy was observed in 104 of 1243 patients (8.4%). There were 35 cases (34%) of ipsilateral palsy and 69 cases (66%) of alternative palsy. The mean age at the onset of the first palsy was 38.9 years old in the ipsilateral group and 48.4 years old in the alternative group, and a significant difference was observed between them. The number of recurrences ranged from 1 to 4. Among the ipsilateral group, 6 patients experienced more than second recurrence. In two cases, the condition failed to resolve after the second recurrence. A serological examination confirmed that 4 cases had recurrent VZV-related palsy (both the first and second palsies were VZV-related) and all of them initially had ZSH: no cases had Hunt syndrome as the first palsy. ConclusionsThe VZV-specific immunity obtained with ZSH might be insufficient to suppress VZV reactivation, and VZV vaccination should be recommended for ZSH patients to prevent further recurrence of VZV-related facial palsy. More than 2 ipsilateral recurrent episodes may be a risk factor for incomplete recovery.

Resolution of Recurrent VZV Myelitis With the Use of Intravenous (IV) Immunoglobulin (IG)

Objective To present a case of a patient with recurrent VZV myelitis successfully treated with Intravenous Immunoglobulin (IVIG). Background VZV myelitis is a rare complication of VZV reactivation that tends to be monophasic. There is no solid evidence for a particular treatment regimen for VZV myelitis. No prior reports or studies have looked at using intravenous immunoglobulin for this condition, particularly for refractory cases. Design/Methods 75 year old female with history of hypertension presented with paresthesia on lateral side of right lower extremity, followed by vesicular rash T2 dermatomal distribution. Over a period of 2 weeks patient started experiencing bilateral lower extremity weakness R&gt;L. CNS imaging revealed C3-C6 enhancing lesion and T2 hyperintense lesion. VZV confirmed by skin biopsy. Lumbar puncture (LP) was remarkable only for mildly elevated protein (67 mg/dL), although this LP was 4 weeks after initial symptoms. Patient was treated initially with 5 days of 1 g IV Solumedrol and valacyclovir 1 g TID with improvement of weakness and rash. However, over the next two years, the patient continued to get occasional vesicles with a flare of her myelitis shortly after valacyclovir down-titration trial. She was started on monthly IVIG (1 g/kg IVIG over 2 days) given her refractory and recurrent myelitis. Since starting monthly IVIG, the patient has not had any more zoster outbreaks or further episodes of myelitis. She has gradually improved her balance and gait as well. Results N/A. Conclusions We present an unusual case of recurrent VZV myelitis successfully treated with monthly IVIG. The successful treatment of this patient with IVIG should prompt consideration for its use in similar cases of recurrent VZV myelitis and may provide insight for future studies on how to treat VZV-related diseases. Rapid initiation of this treatment when the condition is recognized early could significantly improve outcomes and patients' quality of life.

Changes in Immune Function during Initial Military Training.

Initial military training (IMT) is a transitionary period wherein immune function may be suppressed and infection risk heightened due to physical and psychological stress, communal living, and sleep deprivation. This study characterized changes in biomarkers of innate and adaptive immune function, and potential modulators of those changes, in military recruits during IMT. Peripheral leukocyte distribution and mitogen-stimulated cytokine profiles were measured in fasted blood samples, Epstein-Barr (EBV), varicella zoster (VZV), and herpes simplex 1 (HSV1) DNA was measured in saliva by quantitative polymerase chain reaction as an indicator of latent herpesvirus reactivation, and diet quality was determined using the healthy eating index measured by food frequency questionnaire in 61 US Army recruits (97% male) at the beginning (PRE) and end (POST) of 22-wk IMT. Lymphocytes and terminally differentiated cluster of differentiation (CD)4+ and CD8+ T cells increased PRE to POST, whereas granulocytes, monocytes, effector memory CD4+ and CD8+ T cells, and central memory CD8+ T cells decreased ( P ≤ 0.02). Cytokine responses to anti-CD3/CD28 stimulation were higher POST compared with PRE, whereas cytokine responses to lipopolysaccharide stimulation were generally blunted ( P < 0.05). Prevalence of EBV reactivation was higher at POST ( P = 0.04), but neither VZV nor HSV1 reactivation was observed. Diet quality improvements were correlated with CD8+ cell maturation and blunted proinflammatory cytokine responses to anti-CD3/CD28 stimulation. Lymphocytosis, maturation of T-cell subsets, and increased T-cell reactivity were evident POST compared with PRE IMT. Although EBV reactivation was more prevalent at POST, no evidence of VZV or HSV1 reactivation, which are more common during severe stress, was observed. Findings suggest increases in the incidence of EBV reactivation were likely appropriately controlled by recruits and immune-competence was not compromised at the end of IMT.

Identifying optimal vaccination scenarios to reduce varicella zoster virus transmission and reactivation

BackgroundVaricella zoster virus (VZV) is one of the eight known human herpesviruses. Initial VZV infection results in chickenpox, while viral reactivation following a period of latency manifests as shingles. Separate vaccines exist to protect against both initial infection and subsequent reactivation. Controversy regarding chickenpox vaccination is contentious with most countries not including the vaccine in their childhood immunization schedule due to the hypothesized negative impact on immune-boosting, where VZV reactivation is suppressed through exogenous boosting of VZV antibodies from exposure to natural chickenpox infections.MethodsPopulation-level chickenpox and shingles notifications from Thailand, a country that does not vaccinate against either disease, were previously fitted with mathematical models to estimate rates of VZV transmission and reactivation. Here, multiple chickenpox and shingles vaccination scenarios were simulated and compared to a model lacking any vaccination to analyze the long-term impacts of VZV vaccination.ResultsAs expected, simulations suggested that an introduction of the chickenpox vaccine, at any coverage level, would reduce chickenpox incidence. However, chickenpox vaccine coverage levels above 35% would increase shingles incidence under realistic estimates of shingles coverage with the current length of protective immunity from the vaccine. A trade-off between chickenpox and shingles vaccination coverage was discovered, where mid-level chickenpox coverage levels were identified as the optimal target to minimize total zoster burden. Only in scenarios where shingles vaccine provided lifelong immunity or coverage exceeded current levels could large reductions in both chickenpox and shingles be achieved.ConclusionsThe complicated nature of VZV makes it impossible to select a single vaccination scenario as universal policy. Strategies focused on reducing both chickenpox and shingles incidence, but prioritizing the latter should maximize efforts towards shingles vaccination, while slowly incorporating chickenpox vaccination. Alternatively, countries may wish to minimize VZV complications of both chickenpox and shingles, which would lead to maximizing vaccine coverage levels across both diseases. Balancing the consequences of vaccination to overall health impacts, including understanding the impact of an altered mean age of infection for both chickenpox and shingles, would need to be considered prior to any vaccine introduction.

Varicella-Zoster virus reactivation following severe acute respiratory syndrome coronavirus 2 vaccination or infection: New insights

IntroductionVaricella zoster virus (VZV) reactivation has been reported following vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the real extent remains unknown. MethodsWe conducted a systematic review to summarize evidence of VZV reactivation or infection following SARS-CoV-2 vaccination. Episodes after coronavirus disease-2019 (COVID-19) were also identified. Related articles were identified in PubMed and EMBASE databases till December 31, 2021 using the terms “varicella zoster” and “COVID-19″. PROSPERO Register Number: CRD42021289399. ResultsThe search revealed 314 articles, of which 55 met the inclusion criteria. VZV manifestations were documented in 179 (82.1%) subjects following SARS-CoV-2 vaccination and in 39 (17.9%) patients with COVID-19. Among the vaccinated, median (IQR) age was 56.5 (42–70) years, and 56.8% were female. Twenty-one (16.8%) were immunosuppressed. The median (IQR) latency time after vaccination was 6 (3–10) days, and 84.4% received mRNA vaccines. VZV reactivation occurred following a first dose (68.2%), a second dose (12.8%) or a booster (0.6%). The most important VZV manifestation was dermatome herpes zoster rash, which accounted for 86.4% of events in vaccinated subjects. Twenty patients (11.3%) presented serious VZV events after vaccination, with Herpes Zoster ophthalmicus (5.6%) and post-herpetic neuralgia (3.4%) predominating. No VZV pneumonia or deaths were recorded. Antiviral prescriptions were made in 96.2% of vaccinated subjects. No significant differences between vaccinated and infected subjects were found. ConclusionThis study indicates that the occurrence of VZV reactivation is clinically relevant. However, our findings suggest that COVID-19 vaccination is safe, and remains strongly recommended.

Silent Reactivation of Varicella Zoster Virus in Pregnancy: Implications for Maintenance of Immunity to Varicella.

We encountered two cases of varicella occurring in newborn infants. Because the time between birth and the onset of the illness was much shorter than the varicella incubation period, the cases suggested that the infection was maternally acquired, despite the fact that neither mother experienced clinical zoster. Thus, we tested the hypothesis that VZV frequently reactivates asymptomatically in late pregnancy. The appearance of DNA-encoding VZV genes in saliva was used as an indicator of reactivation. Saliva was collected from 5 women in the first and 14 women in the third trimesters of pregnancy and analyzed at two different sites, at one using nested PCR and at the other using quantitative PCR (qPCR). No VZV DNA was detected at either site in the saliva of women during the first trimester; however, VZV DNA was detected in the majority of samples of saliva (11/12 examined by nested PCR; 7/10 examined by qPCR) during the third trimester. These observations suggest that VZV reactivation occurs commonly during the third trimester of pregnancy. It is possible that this phenomenon, which remains in most patients below the clinical threshold, provides an endogenous boost to immunity and, thus, is beneficial.

EXPECT THE UNEXPECTED: A CASE OF VZV-INDUCED HYDRCEPALUS IN A PATIENT WITH RECURRENCE OF CLL

TYPE: Abstract TOPIC: Critical Care INTRODUCTION: Varicella-Zoster virus followed by herpes virus is the 2 most common viral causes of acute Encephalitis/Meningitis, especially in immunocompromised patients. Reactivation of VZV, after the primary chickenpox, generally presents as vesicular rash in one or more dermatomes, preceding or following the main manifestation. Neurological symptoms by VZV are well documented in the elderly, but it is rare to cause hydrocephalus. CASE PRESENTATION: A case of a 70-year-old male with a past medical history of Chronic Lymphocytic Leukemia about 23 years ago presented to the emergency department due to persistent nausea, vomiting, diarrhea, headache, and weakness for 5 days. After the first laboratory examination, a diagnosis of recurrence of CLL was made. He became increasingly lethargic and was started on Ceftriaxone, Azithromycin, and Acyclovir for suspicion of encephalitis. CSF PCR panel was positive for VZV and rhinovirus, negative for bands. He was intubated for airway protection. He underwent leukapheresis twice to reduce leukostasis. On Day 3 of the ICU stay, he remained obtunded, CT head revealed developing hydrocephalus, an external ventricular drain was placed. Repeat CSF revealed persistent positive VZV virus. Over the next few days, he remained comatose with no movements or improvement in neurological status and eventually passed away. DISCUSSION: Immunocompromised patients who have impaired T-cell mediated immunity are prone to viral encephalitis. This is the first reported case of VZV-induced hydrocephalus. CONCLUSIONS: It is important to raise awareness of the risk of VZV reactivation with severe neurological complications in patients with reactivation of malignancy. Acyclovir should be initiated early to prevent complications. DISCLOSURE: Nothing to declare. KEYWORD: VZV

Studies of Infection and Experimental Reactivation by Recombinant VZV with Mutations in Virally-Encoded Small Non-Coding RNA.

Locked-nucleotide analog antagonists (LNAA) to four varicella zoster virus small non-coding RNA (VZVsncRNA 10–13) derived from the mRNA of the open reading frame (ORF) 61 gene individually reduce VZV replication in epithelial cells and fibroblasts. To study the potential roles VZVsncRNA 10–13 have in neuronal infection we generated two recombinant VZV; one in which 8 nucleotides were changed in VZVsncRNA10 without altering the encoded residues of ORF61 (VZVsnc10MUT) and a second containing a 12-nucleotide deletion of the sequence common to VZVsncRNA12 and 13, located in the ORF61 mRNA leader sequence (VZVsnc12-13DEL). Both were developed from a VZV BAC with a green fluorescent protein (GFP) reporter fused to the N terminal of the capsid protein encoded by ORF23. The growth of both mutant VZV in epithelial cells and fibroblasts was similar to that of the parental recombinant virus. Both mutants established productive infections and experimental latency in neurons derived from human embryonic stem cells (hESC). However, neurons that were latently infected with both VZV mutant viruses showed impaired ability to reactivate when given stimuli that successfully reactivated the parental virus. These results suggest that these VZVsncRNA may have a role in VZV latency maintenance and/or reactivation. The extension of these studies and confirmation of such roles could potentially inform the development of a non-reactivating, live VZV vaccine.

Infectious risk in multiple sclerosis patients treated with disease-modifying therapies: A three-year observational cohort study.

BackgroundThe disease-modifying therapies (DMTs) largely used in multiple sclerosis (MS) may result in higher infectious risk.ObjectiveWe aimed to investigate the infectious risk in DMT-treated MS patients.MethodsMS patients were evaluated for infectious risk before starting, switching or during DMT.ResultsIn this three-year observational cohort study 174 MS patients were enrolled. Among them, 18 patients were anti-HBc + and 19 patients were QuantiFERON®-TB Gold In-Tube (QFT) + . No patients with anti-HBc + showed a detectable HBV-DNA and all started DMT. Among QTB + patients, 17 latent TB infections (LTBIs) and 2 active TB infections (TBIs) were identified. After one month of LTBI prophylaxis or TB treatment, respectively, all patients started DMTs.Overall, 149 started DMTs. During DMTs, one ocrelizumab-treated patient with anti-HBc + developed HBV reactivation and six patients (3 on natalizumab, 2 on ocrelizumab and 1 on IFN-β) showed reactivation of HSV-1, with detectable plasma DNA. Finally, 1 cladribine-treated patient experienced VZV reactivation. All the reactivations of latent infections have been successfully treated.ConclusionScreening of infectious diseases in DMT candidate MS patients helps to mitigate the infectious risk. During DMTs, a regular assessment of infectious risk allows to avoid discontinuing MS therapy and guarantees a higher degree of safety.

Post Herpetic Neuralgia - a study of demographics in Cosmopolitan Tertiary Centre in Penang, Malaysia

Post Herpetic Neuralgia (PHN) is a complication of VZV reactivation which remained latent in ganglion of cranial nerves, dorsal root and autonomic nerves. It is characterized by persistent pain, leading to significant psychosocial impact. The study intends to investigate the demographics of patients and sites of PHN in Penang Hospital.