Herpes Zoster Virus Reactivation in a 16 Year Old Female Post COVID-19 Vaccine. Case report and Review of the Literature.

Background: According to WHO, there have been 9205 fatal COVID-19 cases confirmed in Saudi Arabia out of 793,729 cases overall (5). During the development of COVID-19 vaccines, several technologies were used including DNA-based, RNA-based vaccines, non-replicating viral vector vaccines, and inactivated vaccines. Objective: We present a case of varicella zoster virus reactivation post COVID-19 vaccine in a young medically free 16 years old female and review of the literature using the keywords "Herpes Zoster, "varicella zoster"," shingles", "post COVID-19 vaccine", "Post COVID-19 cutaneous manifestations". Methods: The search was conducted in Google Scholar, Scopus, PubMed, and Web of Science data bases. Results: We encountered 241 published studies in regard to post COVID-19 dermatologic manifestations including post COVID-19 vaccine herpes zoster reactivation in the English literature and one case in German. Our case and 4 other reported cases in the literature are patients aged of 20 years old and below. Conclusion: Varicella zoster virus falls under the family of Herpesviridae, It's characterized by its ability to escape host immune system and remain dormant in ganglionic neurons. Reactivation of the infection will result in herpes zoster manifesting as painful vesicles in a dermatomal distribution. Possible link is the suppression of type-one interferons caused by the mRNA-based vaccine such as COVID-19 vaccines. Yet, potential correlation remains to be demonstrated.

Pole-to-pole involvement of varicella zoster virus reactivation following COVID-19 vaccination.

The aim of this study is to report the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management outcomes in a series of three cases of varicella zoster virus (VZV) reactivation following one dose of coronavirus disease 2019 (COVID-19) vaccination. This was a retrospective and observational study. All the patients who developed uveitis post-vaccination were pooled together. Patients who had VZV reactivation were included. Two cases had polymerase chain reaction positive for VZV from aqueous humor. At the time of presentation, IgG and IgM spike protein antibodies for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were tested. Out of this pool, three patients with classical features to describe pole-to-pole manifestations were chosen. A 36-year-old lady with post-vaccination sclerokeratouveitis associated with reactivation of herpes zoster ophthalmicus, a 56-year-old lady with post-vaccination acute anterior uveitis associated with herpes zoster ophthalmicus, and a 43-year-old gentleman with post-vaccination acute retinal necrosis were included. We present a possible link between anti-SARS-CoV-2 virus vaccination and varicella zoster reactivation in these patients and also describe the clinical features, imaging findings including confocal imaging, corneal nerve fiber analysis, and management with detailed discussion.

Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.

Indian data regarding serious neurological and psychiatric adverse events, following coronavirus disease 2019 (COVID-19) vaccination, are lacking. We, therefore, systematically evaluated cases of post-vaccinal serious neurological and psychiatric adverse reactions published from India. A systematic review of cases published from India, which were archived in PubMed, Scopus, and Google Scholar databases, was performed; pre-print databases along with ahead-of-print contents were searched in addition. Retrieved articles, as on June 27, 2022, were evaluated following PRISMA guidelines. EndNote 20 web tool was used to make a PRISMA flow chart. Individual patients' data were compiled in a tabular form. The protocol of the systematic review was registered with PROSPERO (CRD42022324183). A total of 64 records describing 136 instances of serious neurological and psychiatric adverse events were identified. More than 50% (36/64) reports were from the following four states, namely, Kerala, Uttar Pradesh, New Delhi, and West Bengal. The mean age of persons developing these complications was 44.89 ± 15.77 years. In the majority, adverse events occurred within 2 weeks of administration of the first dose of COVISHIELD vaccine. Immune-mediated central nervous system (CNS) disorders were identified in 54 instances. Guillain-Barre syndrome and other immune-mediated peripheral neuropathies were reported in 21 cases. Post-vaccinal herpes zoster was recorded in 31 vaccine recipients. Psychiatric adverse events were recorded in six patients. In Indian recipients of COVID-19 vaccine, a variety of serious neurological complications were reported. The overall risk appears minuscule. Immune-mediated central and peripheral neuronal demyelinations were the most frequently reported post-vaccinal adverse events. A large number of cases of herpes zoster have also been reported. Immune-mediated disorders responded well to immunotherapy.

Inactivated COVID-19 vaccine-related herpes zoster and post-herpetic neuralgia: Three case reports.

Vaccination programs against COVID-19 have been implemented all over the world since December 2020. Beside the common side effects of vaccines, there are also increasing reports of herpes zoster (HZ) activation. In this report, we describe three cases of HZ, one of them with post-herpetic neuralgia (PHN) after receiving inactivated COVID-19 vaccine. The first two patients developed HZ 8 and 10 days after vaccination, respectively. When pain could not be controlled with paracetamol and non-steroidal anti-inflammatories, the patients received weak opioid codeine. In addition, the first patient received gabapentin, and the second patient was applied erector spinae plane block. The third patient was admitted 4 months after the diagnosis of HZ and considered to have PHN and pain palliation was provided with tramadol. Although the exact cause has not yet been fully resolved, increased reports of HZ after vaccination suggests a link between vaccines and HZ. Considering that receiving COVID-19 vaccines will going on, HZ and PHN cases will continue to be seen. More epidemiological studies are needed to further evaluate the relationship between COVID-19 vaccines and HZ.

Long-term risk of herpes zoster following COVID-19: A retrospective cohort study of 2 442 686 patients.

The long-term risk of herpes zoster (HZ) after recovery from a SARS-CoV-2 infection is unclear. This retrospective cohort study assessed the risk of HZ in patients following a COVID-19 diagnosis. This retrospective, propensity score-matched cohort study was based on the multi-institutional research network TriNetX. The risk of incident HZ in patients with COVID-19 was compared with that of those not infected with SARS-CoV-2 during a 1-year follow-up period. Hazard ratios (HRs) and 95% confidence intervals (CIs) of HZ and its subtypes were calculated. This study identified 1 221 343 patients with and without COVID-19 diagnoses with matched baseline characteristics. During the 1-year follow-up period, patients with COVID-19 had a higher risk of HZ compared with those without COVID-19 (HR: 1.59; 95% CI: 1.49-1.69). In addition, compared with the control group patients, those with COVID-19 had a higher risk of HZ ophthalmicus (HR: 1.31; 95% CI: 1.01-1.71), disseminated zoster (HR: 2.80; 95% CI: 1.37-5.74), zoster with other complications (HR: 1.46; 95% CI: 1.18-1.79), and zoster without complications (HR: 1.66; 95% CI: 1.55-1.77). Kaplan-Meier curve analysis (log-rank p < 0.05) results indicated that the risk of HZ remained significantly higher in patients with COVID-19 compared with those without COVID-19. Finally, the higher risk of HZ in the COVID-19 cohort compared with that in the non-COVID-19 cohort remained consistent across subgroup analyses regardless of vaccine status, age, or sex. The risk of HZ within a 12-month follow-up period was significantly higher in patients who had recovered from COVID-19 compared with that in the control group. This result highlights the importance of carefully monitoring HZ in this population and suggests the potential benefit of the HZ vaccine for patients with COVID-19.

Viral meningitis and encephalitis: an update.

PURPOSE OF REVIEW: The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and treatment of the most common causes of viral meningitis and encephalitis worldwide. RECENT FINDINGS: Viral meningitis and encephalitis are increasingly diagnosed as molecular diagnostic techniques and serologies have become more readily available worldwide but recent progress in novel antiviral therapies remains limited. Emerging and re-emerging viruses that have caused endemic or worldwide outbreaks or epidemics are arboviruses (e.g., West Nile virus, Japanese encephalitis, Tick borne encephalitis, Dengue, Zika, Toscana), enteroviruses (e.g., Enterovirus 71, Enterovirus D68), Parechoviruses, respiratory viruses [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, metapneumoviruses, measles, mumps], and herpes viruses [e.g., herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, human herpes (HV) 6, varicella zoster virus (VZV)]. Future efforts should concentrate in increasing availability for those viruses with effective vaccination [e.g., Japanese encephalitis, Tick borne encephalitis, varicella zoster viruses, SARS-CoV-2, influenza], prompt initiation of those with encephalitis with treatable viruses (e.g., HSV-1, VZV), increasing the diagnostic yield by using novel techniques such as metagenomic sequencing and avoiding unnecessary antibiotics in those with viral meningitis or encephalitis. SUMMARY: We review the current epidemiology, clinical presentation, diagnosis, and treatment of the common causative agents of viral meningitis and encephalitis worldwide.

Is Guillain-Barre syndrome following chickenpox a parainfectious disease? A case report and literature review.

BACKGROUND: Polyradiculoneuropathy following infection with varicella zoster virus (VZV) is rare and most of the time, happens in the context of reactivation of latent VZV. We report a case of acute polyradiculoneuropathy following primary infection with VZV marked by atypical clinical features raising the hypothesis of a para-infectious disease. CASE PRESENTATION: We describe a 43-years-old male who developed ataxia, dysphagia, dysphonia, and oculomotor disorders (vertical binocular diplopia and bilateral ptosis) followed by quadriplegia with areflexia which occurred 4 days later. The patient had a history of varicella that occurred 10 days before the onset of these symptoms. Nerve conduction study revealed features consistent with an acute motor-sensory axonal neuropathy (AMSAN). Anti-ganglioside antibodies were negative. Based on clinical presentation and ancillary examination, we retain the Miller Fisher/Guillain-Barré overlap syndrome diagnosis. The patient was treated with high doses of methylprednisolone but the evolution of the disease was nevertheless marked by a complete recovery six weeks after onset of symptoms. CONCLUSION: GBS following varicella is a rare but severe disease occurring most often in adults and marked by greater involvement of the cranial nerves. Its clinical features suggest that it is a para-infectious disease. Antiviral therapy has no effect on the course of the disease but its administration within the first 24 h after the onset of chickenpox in adults can prevent its occurrence.

Varicella zoster virus cerebellitis without skin manifestations in an immunocompetent adult.

The varicella zoster virus (VZV) is a ubiquitous, neurotropic pathogen capable of reactivation from sensory ganglion cells to cause dermatomal herpes zoster infection, alongside a range of pathologies within the central nervous system. The presence of VZV cerebellitis without skin manifestations, however, is exceedingly rare in immunocompetent adults.We report a case of VZV cerebellitis in an immunocompetent woman in her 70s, in the absence of a rash. The patient presented with a 2-week history of progressive gait ataxia, headache and mild confusion. Serological tests and neuroimaging were unremarkable. Diagnosis was confirmed through cerebrospinal fluid (CSF) analysis which revealed lymphocytosis and the presence of VZV DNA on PCR analysis. The patient showed symptomatic improvement following empirical acyclovir treatment, corroborated by favourable CSF analysis 10 days post-treatment initiation.Infective aetiology, including VZV, should be considered in patients presenting with acute cerebellar ataxia, even in immunocompetent adults with an absence of dermatological signs.

Risk of Herpes Zoster in Patients with Pulmonary Tuberculosis-A Population-Based Cohort Study.

BACKGROUND: Pulmonary tuberculosis (TB), a global health problem, is typically caused by the bacterium Mycobacterium tuberculosis. Herpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus (VZV). The reactivation of VZV can be caused by stress. We investigated whether pulmonary TB increases the risk of HZ development. METHODS: This study used data that sampled a population of 2 million people in 2000 from the National Health Insurance Research Database. This cohort study observed Taiwanese patients aged 20-100 years with pulmonary TB from 2000 to 2017 (tracked to 2018). Pulmonary TB was defined as having two or more outpatient diagnoses or at least one admission record. To address potential bias caused by confounding factors, the control cohort and pulmonary TB cohort were matched 1:1 by age, gender, index year, and comorbidities. Patients with HZ before the index date were excluded. RESULTS: A total of 30,805 patients were in the pulmonary TB and control cohorts. The incidence rate of HZ in pulmonary TB and control cohorts were 12.00 and 9.66 per 1000 person-years, respectively. The risk of HZ in the pulmonary TB cohort (adjusted hazard ratios = 1.23; 95% confidence interval = 1.16-1.30) was significantly higher than that of in control cohort. Among patients without comorbidities, the patients with TB were 1.28-fold more likely to have HZ than those without TB. CONCLUSION: Patients with TB should be well treated to avoid the potential risk of HZ occurrence. Although we identified the association between pulmonary TB and HZ, further studies are needed to confirm the result.

Preclinical immunogenicity of an adenovirus-vectored vaccine for herpes zoster.

Herpes zoster (HZ) results from waning immunity following childhood infection with varicella zoster virus (VZV) but is preventable by vaccination with recombinant HZ vaccine or live HZ vaccine (two doses or one dose, respectively). Vaccine efficacy declines with age, live HZ vaccine is contraindicated in immunosuppressed individuals, and severe local reactogenicity of recombinant HZ vaccine is seen in up to 20% of older adults, indicating a potential need for new vaccines. Nonreplicating chimpanzee adenovirus (ChAd) vectors combine potent immunogenicity with well-established reactogenicity and safety profiles. We evaluated the cellular and humoral immunogenicity of ChAdOx1 encoding VZV envelope glycoprotein E (ChAdOx1-VZVgE) in mice using IFN-γ ELISpot, flow cytometry with intracellular cytokine staining, and ELISA. In outbred CD-1 mice, one dose of ChAdOx1-VZVgE (1 × 107 infectious units) elicited higher gE-specific T cell responses than two doses of recombinant HZ vaccine (1 µg) or one dose of live HZ vaccine (1.3 × 103 plaque-forming units). Antibody responses were higher with two doses of recombinant HZ vaccine than with two doses of ChAdOx1-VZVgE or one dose of live HZ vaccine. ChAdOx1-VZVgE boosted T cell and antibody responses following live HZ vaccine priming. The frequencies of polyfunctional CD4+ and CD8+ T cells expressing more than one cytokine (IFN-γ, TNF-α and IL-2) were higher with ChAdOx1-VZVgE than with the conventional vaccines. Results were similar in young and aged BALB/c mice. These findings support the clinical development of ChAdOx1-VZVgE for prevention of HZ in adults aged 50 years or over, including those who have already received conventional vaccines.

Herpes Zoster Following COVID-19 Vaccine Booster.

BACKGROUND Herpes zoster is a condition in which there is reactivation of varicella zoster virus (VZV), which is usually seen in the elderly and those with immunocompromised states. Recently, however, there have been many reports of herpes zoster after administration of COVID-19 vaccines, although initial trials showed that these vaccines have good safety and immunogenicity profiles. At the time of writing, about 5 billion people worldwide had received their full course of COVID-19 vaccination. This case report describes an elderly man who developed herpes zoster after receiving a booster dose of the Pfizer-BioNTech (BNT162b2) vaccine, with no adverse effects after the first and second dose. CASE REPORT An 82-year-old man with underlying type 2 diabetes mellitus, hypertension, dyslipidemia, and cerebrovascular disease presented with left-sided chest and upper back pain. The pain was intermittent, burning in nature, and disturbed his sleep. A week prior to his presentation, he received a COVID-19 vaccine (BNT162b2) booster dose. Examination revealed multiple vesicles along his anterior and posterior T3 dermatome. He was diagnosed with herpes zoster and treated with a course of oral acyclovir. Upon review 7 days later, he had recovered well, with resolution of his vesicles and pain. CONCLUSIONS COVID-19 vaccination remains an important measure to prevent transmission of infection and to reduce the mortality and morbidity caused by it. However, healthcare practitioners should be aware of the possible association between COVID-19 vaccination and herpes zoster. Appropriate explanation and safety advice on the possible adverse events following COVID-19 vaccination, including herpes zoster infection, should be given to patients. This will facilitate early recognition and treatment of this condition.

COVID-19 infection and vaccines: potential triggers of Herpesviridae reactivation.

Since the onset of the COVID-19 outbreak, numerous articles have highlighted a possible link between COVID-19 vaccination or infection and Herpesviridae co-infection or reactivation. The authors conducted an exhaustive literature review on this topic, the results of which are presented individually for each member of the Herpesviridae family: Herpes Simplex Virus (HSV) types-1 (HSV-1) and 2 (HSV-2); Varicella-Zoster Virus (VZV); Epstein-Barr Virus (EBV); Cytomegalovirus (CMV); HHV-6; HHV-7; and HHV-8. These human herpesviruses can serve as prognostic markers for the COVID-19 infection and may even underlie some of the clinical manifestations initially attributed to SARS-CoV-2. In addition to SARS-CoV-2 infection, all corresponding vaccines approved to date in Europe appear capable of inducing herpesvirus reactivation. It is important to consider all viruses of the Herpesviridae family when managing patients infected with or recently vaccinated against COVID-19.

A rare case of AIDS co-infected with COVID-19 presenting with disseminated Herpes zoster complicated with CMV and Varicella zoster virus meningoencephalitis.

During the COVID-19 pandemic, numerous co-infections have been reported, with some studies indicating that patients with HIV/AIDS have worse outcomes when co-infected with COVID-19. Here, we present the case of a young adult male who presented with disseminated Varicella and was simultaneously diagnosed with AIDS and COVID-19 virus with several infection-related complications.  A 25-year-old African-American male presented to the Emergency Department with vesicular, blistering rashes in multiple dermatomes including his eyelids. The screening test in the ED was positive for COVID-19. Given his high-risk sexual history, he was tested for HIV which returned positive with a CD4 count of zero. He was started on IV antivirals for disseminated varicella with zoster ophthalmicus. The patient was intubated for worsening respiratory failure and required intensive care. During the hospital course, he developed worsening encephalopathy and CSF analysis was positive for CMV and VZV. The patient has a prolonged hospital stay and exhibited evidence of infectious CNS vasculitis and HIV myelopathy. Anti-retroviral therapy was started after the acute period and the patient showed slow but definite clinical improvement. To the best of our knowledge, this is the first case report of a patient with AIDS with COVID-19 and disseminated VZV and with multiple complex infection-related complications.

An Unusual Case of Arm Pain in a Young Soccer Player: Herpes Zoster in the Pediatric Athlete.

ABSTRACT: Herpes zoster (HZ), shingles, is caused by the varicella-zoster virus (VZV). HZ develops as a reactivation of latent VZV and is characterized by a painful, vesicular rash typically manifesting in a dermatomal distribution on the arms, trunk or face. HZ occurs in individuals who had primary VZV disease (chickenpox) as a child or in those who have received live, attenuated VZV vaccine. HZ is common in the elderly and the immunocompromised, with age being the single greatest risk factor. The incidence of HZ in children is 74/100,000 person years for the unvaccinated and 38/100,000 person years for the vaccinated. We discuss the case of a 12-year-old soccer player with HZ who presented with right arm pain after a putative traumatic event. Diagnosis was made after two emergency department visits where the condition was not identified. HZ should be considered in the clinician's differential even in immunocompetent, vaccinated children.

LNP-CpG ODN-adjuvanted varicella-zoster virus glycoprotein E induced comparable levels of immunity with Shingrix™ in VZV-primed mice.

Latent varicella-zoster virus (VZV) may be reactivated to cause herpes zoster, which affects one in three people during their lifetime. The currently available subunit vaccine Shingrix™ is superior to the attenuated vaccine Zostavax® in terms of both safety and efficacy, but the supply of its key adjuvant component QS21 is limited. With ionizable lipid nanoparticles (LNPs) that were recently approved by the FDA for COVID-19 mRNA vaccines as carriers, and oligodeoxynucleotides containing CpG motifs (CpG ODNs) approved by the FDA for a subunit hepatitis B vaccine as immunostimulators, we developed a LNP vaccine encapsulating VZV-glycoprotein E (gE) and CpG ODN, and compared its immunogenicity with Shingrix™ in C57BL/6J mice. The results showed that the LNP vaccine induced comparable levels of gE-specific IgG antibodies to Shingrix™ as determined by enzyme-linked immunosorbent assay (ELISA). Most importantly, the LNP vaccine induced comparable levels of cell-mediated immunity (CMI) that plays decisive roles in the efficacy of zoster vaccines to Shingrix™ in a VZV-primed mouse model that was adopted for preclinical studies of Shingrix™. Number of IL-2 and IFN-γ secreting splenocytes and proportion of T helper 1 (Th1) cytokine-expressing CD4+ T cells in LNP-CpG-adjuvanted VZV-gE vaccinated mice were similar to that of Shingrix™ boosted mice. All of the components in this LNP vaccine can be artificially and economically synthesized in large quantities, indicating the potential of LNP-CpG-adjuvanted VZV-gE as a more cost-effective zoster vaccine.

Willingness to accept herpes zoster vaccines and the influencing factors in China.

BACKGROUND: Herpes zoster increases the burden on the elderly in an aging society. Although an effective vaccine licensed by China Food and Drug Administration in 2019 was introduced into the market in June 2020, the willingness and influencing factors of herpes zoster vaccines in Chinese adults ≥ 50-years-old during coronavirus disease-2019 pandemic are yet to be elucidated. METHODS: An online questionnaire survey was conducted using a simple random sampling method in October 2021 for viewers of the broadcast program. A binary logistic regression and multiple response analysis were conducted for herpes zoster vaccine and vaccination willingness. Pareto's graphs were plotted to present the multiple-choice questions of influencing factors. RESULTS: A total of 3838 eligible participants were included in this study. Among them, 43.02% intended to be vaccinated, including 10.34% self-reported about receiving at least one shot of shingles vaccine, 30.22% declined, and 26.76% were hesitant. This population comprised a large proportion of middle-aged and older people (≥ 50-years-old) who have not experienced an episode of herpes zoster (54.98%) or are unaware of the virus (33.22%). The strongest determinants of vaccine hesitancy among older people were education background of Master's degree or above compared to senior high or equivalent and below, personal monthly income < 3000 RMB compared to 3000-5999 RMB, and living in a rural area. CONCLUSIONS: The willingness to get shingles vaccines can be improved further. Professional education and credible recommendation might prompt the elderly to improve their willingness and reassure them of the safety and efficacy of the vaccine. Also, accessibility and affordability should also be improved in the future.

Herpes zoster after COVID vaccination.

COVID-19 presents in various ways, but mainly as a pulmonary disease (Marzano, 2020). Skin manifestations have been reported, including reactivation of the varicella-zoster virus (Marzano, 2020). Our case report describes two adults developing herpes zoster after vaccination with tozinameran (the Pfizer-BioNTech COVID-19 mRNA vaccine). A possible cause for this reaction is a transient lymphocytopenia that occurs after the vaccination - similar to that in COVID-19 disease (Mulligan, 2020; Wang, 2020; Qin, 2020; Brabilla, 2020; Wang, 2020; Wei, 2017). In the context of vaccinating older and/or immunocompromised adults, our observations can be the starting point for further evaluation of a possible relationship between COVID-19, COVID vaccines, and herpes zoster.

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.