Primary Varicella Zoster Virus Research Articles

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.

P714 Immunogenicity and safety of adjuvated recombinant zoster vaccine in IBD patients on different immunosuppressive therapies

Abstract Background Aberrant immune regulation and the use of immunosuppressive therapy make IBD patients more susceptible to complications of primary Varicella Zoster Virus (VZV) infection and significantly increase the risk of Herpes Zoster (HZ). HZ can be prevented by vaccination and RZV is the first HZ vaccine approved for immunocompromised persons. Limited data on immunogenicity and safety of RZV in immunosuppressed IBD patients are available. We investigated humoral and cell-mediated response and safety of RVZ vaccination in IBD patients under different immunosoppressive therapies. Methods In this prospective single centre study, adult IBD patients were enrolled and vaccinated with 2 doses of RZV between May and July 2022. Different immunosuppressive regimens (anti-metabolites, anti-TNF mono and combination therapy; ustekinumab and vedolizumab monotherapy; mofetyl mycofenolate/steroid combination therapy) were not discontinued and the administration schedule maintained. Immunogenicity was evaluated by quantitative detection of serum IgG anti-VZV antibodies and anti-VZV glycoprotein E (gE) antibodies before and 1 month after vaccination completion using ELISA. Reactogenicity was evaluated by diary cards reporting adverse events for 7 days after each dose. Events were graded from 1 (mild, not interfering with everyday activities) to 3 (severe, preventing normal everyday activities). Disease activity was assessed by SCCAI and HBI before vaccination, 7 and 30 days after each dose. Results Vaccination was completed in 104 (98.1%) out of 106 enrolled patients (median age 49.7 years, 59.4% male; 55.7% UC, 44.3% CD). Humoral response was observed in all patients, with a significant increase of anti-VZV antibodies (median UTI 23.8; IQR: 20.2-26.2 vs median UTI 419; IQR: 20.2-26.2, 376-458, p<0.001, median 17.8 fold increase, figure 1) and anti-gE antibody concentration compared to baseline (median OD 0.24; IQR: 0.21-0.26 vs OD 0.53; IQR:0.4-0.6, median 2.3 fold increase, p<0.001, figure 1). Imunosuppressive agents, either in mono or combination therapy, did not influence anti-VZV titre, anti-gE concentration and CMI response. Local and systemic solicited reactions after any dose were reported in 96.2% (grade 3=24.8%) and 88.6% (grade 3=33.3%) of patients respectively, with higher grade of intensity after the second dose. No severe adverse events related to vaccination were observed; 2 patients (1.9%) reported a disease flare. Conclusion RZV vaccine is able to induce a robust gE-specific humoral immune response. The type and intensity of immunosuppressive regimens did not influence humoral immunogenicity. RZV vaccination was safe and well tolerated in terms of both reactogenicity and exacerbation of disease.

Guillain-Barré syndrome following varicella-zoster virus infection: a case report and systematic review.

Guillain-Barré syndrome (GBS) is an acute inflammatory disease of the peripheral nervous system, rarely following Varicella-zoster virus (VZV) infection. The authors aimed to review all cases in the English literature of GBS that occurred after primary VZV infection to investigate the clinical features, diagnostic workup, treatment, and outcome of patients with GBS following VZV. PubMed, Scopus, and Embase are systematically searched from their inception to 9 May 2022 to collect all cases of GBS following varicella-zoster infection. Patients with GBS following VZV reactivation were excluded. Among the 29 patients, the age of presentation ranged from 1.5 to 70 years with a median of 37, with a yield for males (81.5%). Most of the patients presented with sensory-motor symptoms (65.4%) and suffered from tetraparesis (81.5%). Cranial nerve palsy was present in (84%) of patients, and the seventh cranial nerve was the most commonly affected nerve (75%). Lumbar puncture showed albuminocytological dissociation in (80%) of patients. The dominant nerve conduction study subtype was acute inflammatory demyelinating polyneuropathy (65.3%). in addition, the magnetic resonance imaging showed pathological findings in only (47.5%) of the patients. Intravenous immunoglobulin is now the drug of choice for all cases of GBS following VZV infection. GBS is a rare neurological complication of primary infection with VZV. However, the authors should suspect this syndrome when a patient develops ascending weakness, regardless of the absence of areflexia and albuminocytological dissociation. Drug therapy with IIVIg ensures a gradual improvement for the patient over a period of weeks to several months.

Neurological Complications of Primary Varicella Zoster Virus Infection in Children- Case Reports

Neurological Complications of Primary Varicella Zoster Virus Infection in Children- Case Reports

Creating the "Dew Drop on a Rose Petal": the Molecular Pathogenesis of Varicella-Zoster Virus Skin Lesions.

Varicella-zoster virus (VZV) is a human alphaherpesvirus that causes varicella (chicken pox) as the primary infection in a susceptible host. Varicella is very contagious through its transmission by direct contact with vesicular skin lesions that contain high titers of infectious virus and respiratory droplets. While the clinical manifestations of primary VZV infection are well recognized, defining the molecular mechanisms that drive VZV pathogenesis in the naive host before adaptive antiviral immunity is induced has been a challenge due to species specificity. This review focuses on advances made in identifying the differentiated human host cells targeted by VZV to cause varicella, the processes involved in viral takeover of these heterogenous cell types, and the host cell countermeasures that typically culminate in a benign illness. This work has revealed many unexpected and multifaceted mechanisms used by VZV to achieve its high prevalence and persistence in the human population.

Dynamical study of varicella-zoster virus model in sense of Mittag-Leffler kernel

The primary varicella-zoster virus (VZV) infection that causes chickenpox (also known as varicella), spreads quickly among people and, in severe circumstances, can cause to fever and encephalitis. In this paper, the Mittag-Leffler fractional operator is used to examine the mathematical representation of the VZV. Five fractional-order differential equations are created in terms of the disease’s dynamical analysis such as S: Susceptible, V: Vaccinated, E: Exposed, I: Infectious and R: Recovered. We derive the existence criterion, positive solution, Hyers–Ulam stability, and boundedness of results in order to examine the suggested fractional-order model’s wellposedness. Finally, some numerical examples for the VZV model of various fractional orders are shown with the aid of the generalized Adams–Bashforth–Moulton approach to show the viability of the obtained results.

Preventing varicella zoster infection in immunocompromised adults with varicella zoster-specific immunoglobulins.

Varicella zoster virus (VZV) exposure seriously threatens immunocompromised hosts. Postexposure prophylaxis (PEP) using immune globulins is considered the standard of care; however, the available literature is mainly based on its use in pediatric patients. Here, we describe a widespread VZV exposure among immunocompromised adults treated with VZV-specific immunoglobulins (VZVSIG), and we discuss management and outcomes. We conducted a retrospective study to describe the exposure of immunocompromised patients to a single healthcare worker with primary VZV in 2019. Patients were grouped by their overall risk for infection, and those at risk received a single intramuscular dose of 625 IU of VZVSIG and were followed for 1 year. In total, 83 patients received PEP at <96 hours of exposure: 14 were hospitalized, 68 were outpatients, and 1 was an immunocompromised staff member. The median age was 69 years (range, 21-92), and 49.4% were male. In addition, 30% of the patients were deemed high risk, 42% were intermediate risk, and 28% were considered low risk, although they were given PEP. Varicella infection was not diagnosed in any patient in the first weeks of follow-up. However, during the year of follow-up, 4 patients developed symptoms suspicious of VZV, all >3 months after exposure, thus were probably unrelated to the event. Adverse events related to VZVSIG (pyrexia) were reported in 2 patients (2.4%). Our findings demonstrate the utility of VZVSIG as PEP in one of the largest cohorts of immunocompromised adults to date. No early varicella infection was found following exposure, supporting the current recommendations of the VZVSIG administration.

Current scenario and future applicability of antivirals against herpes zoster.

Herpes zoster (HZ) is a common disease in the aging population and immunocompromised individuals, with a lifetime risk of 20%-30% that increases with age. HZ is caused by reactivation of the varicella-zoster virus (VZV), which remains latent in the spinal dorsal root ganglia and cranial sensory ganglia after resolution of the primary VZV infection. The main focus of HZ management is rapid recovery from VZV infection as well as the reduction and prevention of zoster-associated pain (ZAP) and postherpetic neuralgia (PHN). The use of antivirals against VZV is essential in the treatment of HZ. However, limited antivirals are only licensed clinically for the treatment of HZ, including acyclovir, valacyclovir, famciclovir, brivudine, and amenamevir. Fortunately, some new antivirals against different types of Herpesviridae have been investigated and suggested as novel drugs against VZV. Therefore, this review focuses on discussing the difference in efficacy and safety in the currently licensed antivirals for the treatment of HZ, the applicability of future novel antivirals against VZV, and the preventive or therapeutic effects of these antivirals on ZAP or PHN.

High Incidence of Herpes Zoster in Patients Using Ruxolitinib for Myeloproliferative Neoplasms: Need for Prophylaxis.

High Incidence of Herpes Zoster in Patients Using Ruxolitinib for Myeloproliferative Neoplasms: Need for Prophylaxis.

Infections with Herpes simplex and Varicella zoster virus.

Human herpes viruses belong to the DNA viruses and are among the most common viral pathogens. Currently, eight human herpes viruses have been characterized. Primary infection is typically followed by virus latency. Viral reactivations are more often symptomatic than primary infections and lead more often to medical consultation. In daily practice, infections with herpes simplex virus (HSV) and varicella zoster virus (VZV) are the most common. If HSV primary infections become clinically manifest, they are often accompanied by systemic symptoms whereas manifest HSV reactivations are usually harmless, self-limiting and present as grouped vesicles on an erythematous base (herpetiform). Primary VZV infection leads to the clinical picture of varicella (chickenpox). VZV reactivation manifests clinically as shingles and can be accompanied by severe acute neuralgiform pain. In immunosuppression, complicated (necrotizing, ulcerative, hemorrhagic, generalized) manifestations may occur. The diagnosis is usually made clinically. Therapeutic options include topical agents and systemic antivirals. Adequate therapeutic management includes the recognition and treatment of complications such as the possible involvement of other organ systems and pain. Infection during pregnancy may result in transmission to the unborn child.

Cellular Immune Response after Vaccination with an Adjuvanted, Recombinant Zoster Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Hematopoietic stem cell transplant (HSCT) recipients have a high risk of developing primary varicella-zoster virus (VZV) infection and reactivation. VZV vaccination may prevent infection and reactivation. In the current study, recipients of allogeneic HSCT (34 females, 45 males) were vaccinated with adjuvanted, recombinant zoster vaccine Shingrix™, which contains the VZV glycoprotein E. Cellular immunity against various VZV antigens was analyzed by interferon-gamma ELISpot. Peripheral blood mononuclear cells (PBMC) of recipients with versus without prior shingles (n = 36 and n = 43, respectively) showed approximately twofold higher VZV-specific responses prior to and post vaccination. After the first and second vaccination, ELISpot responses towards the glycoprotein E were significantly higher in males versus females (median of spots increment 18 versus 1 and 17 versus 4, respectively, p ≤ 0.02 each). Multivariate analysis showed that shingles and sex both impacts significantly on VZV immunity. Whereas vaccination-induced changes could hardly be detected after stimulation with a whole VZV antigen, there was a significant increase in responses towards glycoprotein E after vaccination (p < 0.005). These data indicate that vaccination with Shingrix™ augmented cellular, VZV-specific immunity in HSCT recipients. Shingles and male sex could both be identified as factors leading to increased immunity.

Characteristics of herpes zoster infection in patients with COVID-19: a systematic scoping review.

BackgroundAlthough there is literature reporting correlations between varicella zoster virus (VZV) infections and COVID‐19, insufficient evidence exists in this regard. This scoping review aims to identify the existing evidence regarding clinical characteristics of primary VZV infection or reactivation in COVID‐19.MethodsFollowing the PRISMA Extension for Scoping Reviews, MEDLINE and EMBASE were searched for all peer‐reviewed articles with relevant keywords including “Zoster,” “Herpes,” and “COVID‐19” from their inception to November 20, 2021.ResultsA total of 19 articles with three observational studies and 16 case reports or series were included. Primary VZV infections or reactivation were observed in 25 patients. Forty‐eight percent of the patients had disseminated VZV infection. The median time of VZV‐related rash after the onset of respiratory symptoms was 7.0 days (interquartile range: 0–18.8). Those with COVID‐19 and primary VZV infection or reactivation had low lymphocyte counts with a median of 0.67 × 103/μl.ConclusionThis scoping review identified uncertainty and a lack of strong evidence to see the association between primary VZV infection or reactivation and COVID‐19. However, those with COVID‐19 may be more likely to have disseminated VZV, which poses an additional challenge from an infection prevention standpoint. Future studies are warranted to determine the association between primary VZV infection or reactivation and long‐term consequences related to COVID‐19.

Infecciones por el virus del grupo herpes

The Herpesviridae family includes nine subtypes that are pathogenic in human beings. They belong to three subfamilies: α-herpesvirus (herpes simplex 1 and 2, varicella zoster, and herpes B virus); β-herpesvirus (cytomegalovirus, human herpesvirus 6, and human herpesvirus 7), and γ-herpesvirus (Epstein-Barr virus and human herpesvirus 8). All herpesviruses have in common the ability to establish latency and reactive in situations of immunosuppression. Primary herpes simplex 1 and 2 infection remains latent in regional nerve ganglions and has periodic reactivations. It has a lower morbidity than the original infection. The primary varicella zoster virus infection is responsible for varicella whereas the reactivations manifest as shingles. Herpesvirus type 6A gives rise to encephalitis in adults and herpesvirus type 6B gives rise to sudden exanthem in children. Herpesvirus type 8 is associated with Kaposi's sarcoma, multicentric Castleman disease, and body cavity lymphoma.

Rational Design of a Skin- and Neuro-Attenuated Live Varicella Vaccine: A Review and Future Perspectives.

Primary varicella-zoster virus (VZV) infection causes varicella, which remains a prominent public health concern in children. Current varicella vaccines adopt the live-attenuated Oka strain, vOka, which retains the ability to infect neurons, establish latency and reactivate, leading to vaccine-associated zoster in some vaccinees. Therefore, it is necessary to develop a safer next-generation varicella vaccine to help reduce vaccine hesitancy. This paper reviews the discovery and identification of the skin- and neuro-tropic factor, the open reading frame 7 (ORF7) of VZV, as well as the development of a skin- and neuro-attenuated live varicella vaccine comprising an ORF7-deficient mutant, v7D. This work could provide insights into the research of novel virus vaccines based on functional genomics and reverse genetics.

Never Too Old: A Case of Chicken Pox in an Eighty-One-Year-Old Patient

Varicella-zoster virus is a human herpes virus that can present in either an acute (varicella) or latent form (herpes zoster). Varicella is rarely encountered in immunocompetent adults. Since the introduction of the varicella vaccine in 1995 as a part of the standard childhood vaccination program, primary Varicella-zoster virus infection has become rare.1,2

Severe acute respiratory syndrome coronavirus 2, primary varicella zoster virus coinfection, and a polymicrobial ventilator-associated tracheobronchitis in an adult immunocompetent male: a case report

BackgroundThe spectrum of clinical manifestations and differential diagnosis associated with coronavirus disease 2019 is broad, ranging from fever and cutaneous eruptions to respiratory distress or even neurological disorders. Coexisting multipathogen infections significantly increase the complexity of the proper diagnostic and therapeutic approach and correlate with the rate of intensive care unit admissions and in-hospital mortality.Case presentationWe present a case of multipathogen respiratory infection with severe acute respiratory syndrome coronavirus 2, varicella zoster virus, and polymicrobial tracheobronchitis in a 48-year-old Caucasian male hospitalized after traumatic brain injury. The patient tested positive for severe acute respiratory syndrome coronavirus 2 infection upon admission. During his stay in the intensive care unit, the patient developed a vesicular exanthema along with respiratory failure and signs of septic shock.ConclusionThis case of an adult presenting with severe acute respiratory syndrome coronavirus 2 infection and simultaneous primary varicella zoster virus infection illustrates the importance of considering coinfections in patients with coronavirus disease 2019 with unusual clinical manifestations.

Detection of Circulating VZV-Glycoprotein E-Specific Antibodies by Chemiluminescent Immunoassay (CLIA) for Varicella-Zoster Diagnosis.

Varicella and herpes zoster are mild symptoms-associated diseases caused by varicella–zoster virus (VZV). They often cause severe complications (disseminated zoster), leading to death when diagnoses and treatment are delayed. However, most commercial VZV diagnostic tests have low sensitivity, and the most sensitive tests are unevenly available worldwide. Here, we developed and validated a highly sensitive VZV diagnostic kit based on the chemiluminescent immunoassay (CLIA) approach. VZV-glycoprotein E (gE) was used to develop a CLIA diagnostic approach for detecting VZV-specific IgA, IgG, and IgM. The kit was tested with 62 blood samples from 29 VZV-patients classified by standard ELISA into true-positive and equivocal groups and 453 blood samples from VZV-negative individuals. The diagnostic accuracy of the CLIA kit was evaluated by receiver-operating characteristic (ROC) analysis. The relationships of immunoglobulin-isotype levels between the two groups and with patient age ranges were analyzed. Overall, the developed CLIA-based diagnostic kit demonstrated the detection of VZV-specific immunoglobulin titers depending on sample dilution. From the ELISA-based true-positive patient samples, the diagnostic approach showed sensitivities of 95.2%, 95.2%, and 97.6% and specificities of 98.0%, 100%, and 98.9% for the detection of VZV-gE-specific IgA, IgG, and IgM, respectively. Combining IgM to IgG and IgA detection improved diagnostic accuracy. Comparative analyses on diagnosing patients with equivocal results displaying very low immunoglobulin titers revealed that the CLIA-based diagnostic approach is overall more sensitive than ELISA. In the presence of typical VZV symptoms, CLIA-based detection of high titer of IgM and low titer of IgA/IgG suggested the equivocal patients experienced primary VZV infection. Furthermore, while no difference in IgA/IgG level was found regarding patient age, IgM level was significantly higher in young adults. The CLIA approach-based detection kit for diagnosing VZV-gE-specific IgA, IgG, and IgM is simple, suitable for high-throughput routine analysis situations, and provides enhanced specificity compared to ELISA.

Mutagenesis of the Varicella-Zoster Virus Genome Demonstrates That VLT and VLT-ORF63 Proteins Are Dispensable for Lytic Infection.

Primary varicella-zoster virus (VZV) infection leads to varicella and the establishment of lifelong latency in sensory ganglion neurons. Reactivation of latent VZV causes herpes zoster, which is frequently associated with chronic pain. Latent viral gene expression is restricted to the VZV latency-associated transcript (VLT) and VLT-ORF63 (VLT63) fusion transcripts. Since VLT and VLT63 encode proteins that are expressed during lytic infection, we investigated whether pVLT and pVLT-ORF63 are essential for VZV replication by performing VZV genome mutagenesis using CRISPR/Cas9 and BAC technologies. We first established that CRISPR/Cas9 can efficiently mutate VZV genomes in lytically VZV-infected cells through targeting non-essential genes ORF8 and ORF11 and subsequently show recovery of viable mutant viruses. By contrast, the VLT region was markedly resistant to CRISPR/Cas9 editing. Whereas most mutants expressed wild-type or N-terminally altered versions of pVLT and pVLT-ORF63, only a minority of the resulting mutant viruses lacked pVLT and pVLT-ORF63 coding potential. Growth curve analysis showed that pVLT/pVLT-ORF63 negative viruses were viable, but impaired in growth in epithelial cells. We confirmed this phenotype independently using BAC-derived pVLT/pVLT-ORF63 negative and repaired viruses. Collectively, these data demonstrate that pVLT and/or pVLT-ORF63 are dispensable for lytic VZV replication but promote efficient VZV infection in epithelial cells.

Acute Urinary Retention Following Primary VaricellaZoster Virus Infection

Background Acute urinary retention following primary varicella-zoster virus infection (chickenpox) is very rare. Case Presentation We present a case of 34 years old male patient presented with acute urinary retention following primary varicella-zoster virus infection (chickenpox), there was no lesion detected neither by MRI brain nor whole spinal cord imaging. There was a typical blistering rash over the face, trunk, back and upper limbs but sparing the perennial and perianal area. Conclusion Once herpes zoster is found in lumbar lumbosacral region be alert there is possibility of voiding dysfunction like acute retention of urine. The effective treatment plan includes antiviral therapy and urethral catheterization. Most of urological symptoms due to herpes zoster subsides in the very short duration with active guideline treatment. Keywords: Varicella-zoster virus infection; Blister-like rash; Acute urinary retention.

A58 HERPES ZOSTER VIRUS INFECTION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE: SINGLE CENTER EXPERIENCE

Abstract Background Patients with IBD receive a variety of medications that modulate the immune response. However, many medications render patients more susceptible to opportunistic infections. Varicella zoster virus (VZV) infection, in particular, has been well reported in IBD patients, mostly in CD. Chickenpox results from primary VZV infection, and is predominantly seen in the pediatric population. Primary prevention via vaccination for VZV, plays an important role in preventing infections in IBD patients before they start immunomodulators, corticosteroid or biologic therapy. Given the advent of zoster vaccines, it is important to determine if IBD patients should be considered for immunization at a younger age. Aims 1) To document the prevalence of herpes zoster virus (HZV) infection patients with IBD and to further investigate the characteristics of susceptible hosts 2) To assess the severity of herpes zoster in this patient population Methods A single center retrospective cohort study was conducted at the Montreal Children’s Hospital. Pediatric IBD patients (age &amp;lt; 18 years) who developed HZV from 2004- 2019 were identified. Data regarding HZV infection, location, severity, treatment, complications and list of all immunosuppressive medications at the time of HZV infection were retrieved as well as data regarding demographics, medical history, vaccination status including Varicella vaccine, and disease behavior. Results A total of 9 patients were identified from who had VZV infection or HZV. Eight out of 9 patients, had CD and one patient had UC, and 6 out of 8 CD patients had had extensive disease. The vaccine status was up to date in 6 out of 9 patients, and varicella serology was identified prior to starting steroids or biologic agents. Eight out of nine patients were on biologics. Eight patients had local disease, skin only, and one patient had systemic disease with HZV meningitis. Four out of 9 patients had their biologic medications either stopped or the next doses were delayed, while other medications including steroids, methotrexate, thiopurines were continued. Five patients were treated with intravenous acyclovir then oral valacyclovir. The rest started on oral valacyclovir and then switched to intravenous acyclovir due to systemic disease. The overall prognosis of the illness was good, and it resulted in full resolution, including the meningitis case. Conclusions Our study suggests that being on biologic medication plays a significant role in increasing the chances of reactivation of HZV. Although the severity of the HZV infection in our study is limited to skin involvement, there was one systemic infection. Close attention and mandatory documentation of vaccination status is prudent especially prior to starting immunosuppressive medications. Further studies are needed to determine if these patients should be vaccinated with recombinant zoster vaccine. Funding Agencies None