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.

Herpesviral encephalitis associated with bortezomib use in a patient with multiple myeloma and associated light-chain amyloidosis.

INTRODUCTION: Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce. CASE REPORT: A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid. MANAGEMENT & OUTCOME: The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.

Herpes Zoster after mRNA COVID-19 Vaccination: A Case Series.

We present seven immunocompetent patients devoid of any comorbidities and risk factors, who developed for the first time in their life varicella-zoster virus (VZV) reactivation shortly after 1st (four patients) and 2nd dose (three patients) of mRNA COVID-19 vaccines.All four patients who exhibited herpes zoster after the 1st dose of vaccine received the 2nd dose without any adverse reactions or complications. Oral treatment prescribed to all patients with valacyclovir (Valtrex 1 mg tds/day) for 5-7 days led to a complete resolution of symptoms, and rashes disappeared within 9-14 days. Presently, All patients have completed a 3-4½-month follow-up without any evidence of complications and/or recurrence of herpes zoster. (SKINmed. 2022;20:284-288).

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

INTRODUCTION: Varicella 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: This 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.

Fraternal Twins: The Enigmatic Role of the Immune System in Alphaherpesvirus Pathogenesis and Latency and Its Impacts on Vaccine Efficacy.

Although the establishment, maintenance and reactivation from alphaherpesvirus latency is far from fully understood, some things are now manifestly clear: Alphaherpesvirus latency occurs in neurons of the peripheral nervous system and control of the process is multifactorial and complex. This includes components of the immune system, contributions from non-neuronal cells surrounding neurons in ganglia, specialized nucleic acids and modifications to the viral DNA to name some of the most important. Efficacious vaccines have been developed to control both acute varicella and zoster, the outcome of reactivation, but despite considerable effort vaccines for acute herpes simplex virus (HSV) infection or reactivated lesions have thus far failed to materialize despite considerable effort. Given the relevance of the immune system to establish and maintain HSV latency, a vaccine designed to tailor the HSV response to maximize the activity of components most critical for controlling reactivated infection might limit the severity of recurrences and hence reduce viral transmission. In this review, we discuss the current understanding of immunological factors that contribute to HSV and VZV latency, identify differences between varicella-zoster virus (VZV) and HSV that could explain why vaccines have been valuable at controlling VZV disease but not HSV, and finish by outlining possible strategies for developing effective HSV vaccines.

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

BACKGROUND: Although 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. METHODS: Following 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. RESULTS: A 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. CONCLUSION: This 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.

Real-world evidence from over one million COVID-19 vaccinations is consistent with reactivation of the varicella-zoster virus.

BACKGROUND: Reactivation of the varicella-zoster virus (VZV), which causes herpes zoster (HZ, synonym: shingles) in humans, can be a rare adverse reaction to vaccines. Recently, reports of cases after COVID-19 vaccination have arisen. OBJECTIVES: The aim of this study was to assess whether the frequency of HZ is found to increase after COVID-19 vaccination in a large cohort, based on real-world data. As a hypothesis, the incidence of HZ was assumed to be significantly higher in subjects who received a COVID-19 vaccine (Cohort I) vs. unvaccinated individuals (Cohort II). METHODS: The initial cohorts of 1 095 086 vaccinated and 16 966 018 unvaccinated patients were retrieved from the TriNetX database and were matched on age and gender in order to mitigate confounder bias. RESULTS: After matching, each cohort accounted for 1 095 086 patients. For the vaccinated group (Cohort I), 2204 subjects developed HZ within 60 days of COVID-19 vaccination, while among Cohort II, 1223 patients were diagnosed with HZ within 60 days after having visited the clinic for any other reason (i.e. not vaccination). The risk of developing shingles was calculated as 0.20% and 0.11% for cohort I and cohort II, respectively. The difference was statistically highly significant (P < 0.0001; log-rank test). The risk ratio and odds ratio were 1.802 (95% confidence interval [CI] = 1.680; 1.932) and 1.804 (95% CI = 1.682; 1.934). CONCLUSIONS: Consistent with the hypothesis, a higher incidence of HZ was statistically detectable post-COVID-19 vaccine. Accordingly, the eruption of HZ may be a rare adverse drug reaction to COVID-19 vaccines. Even though the molecular basis of VZV reactivation remains murky, temporary compromising of VZV-specific T-cell-mediated immunity may play a mechanistic role in post-vaccination pathogenesis of HZ. Note that VZV reactivation is a well-established phenomenon both with infections and with other vaccines (i.e. this adverse event is not COVID-19-specific).

COVID-19 pandemic as a risk factor for the reactivation of herpes viruses.

The appearance on the skin of herpes virus lesions, concomitantly with the coronavirus disease 2019 (COVID-19) pandemic, leads us to suspect an underlying infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagnostic reverse transcriptase polymerase chain reaction tests and immunoglobulin M (IgM) and IgG seroconversion studies have therefore been carried out. We present three cases of herpes virus infections in immunocompetent patients: one of the infections was herpes simplex 1 in a 40-year-old woman, and the other two were herpes varicella-zoster infections in a 62-year-old man and a 25-year-old woman. The patients were in the care of the southern health district of Seville of the SAS (Andalusian Health Service) during the Spanish state of alarm over the COVID-19 pandemic. The SARS-CoV-2 infection was confirmed in only one of the three cases. In this study, we briefly review the etiopathogenic role of the COVID-19 pandemic situation, whereby immunodeficiencies are generated that favour the appearance of other viral infections, such as herpes virus infections.

Herpes simplex and herpes zoster viruses in COVID-19 patients.

BACKGROUND: Reactivation of herpes family viruses in immunocompromised patients may result in detrimental outcomes for the hosts; therefore, herpes simplex virus-1 and varicella zoster virus infections in the context of COVID-19 may have clinical and prognostic implications. Several reports associated this human herpes virus with COVID-19 infection and have claimed that it can be an indicator for latent COVID-19 infection. However, since most of these were case reports, it is impossible to assess the prevalence of these associations. METHODS: The University of Florida patient registry i2b2 with ICD-10 diagnosis codes was used for retrieval of patients with diagnosis of COVID-19 and each of the other viruses over the period of October 2015-June 2020. RESULTS: The prevalence of the herpes simplex-1 occurrence in the COVID-19 group was 2.81% compared to 0.77% in the hospital population odds ratio of 5.27. When adjusted for gender, race, and age, the odds were 5.18, 4.48, and 4.61, respectively. After adjustment for respiratory disease, endocrine disease, obesity, diabetes, circulatory disease, and smoking, the odds were 1.94, 3.18, 1.37, 3.54, 3.7, and 5.1, respectively. The prevalence of the varicella zoster virus in COVID-19 patients was 1.8% compared to 0.43% in the hospital population, odds ratio of 5.26 before adjustment, and 5.2, 5.47, and 4.76 after adjusting for gender, age, and race, respectively. When adjusted for respiratory disease, endocrine disease, obesity, diabetes, and circulatory and neurological diseases, the odds were 1.3, 2.2, 1.48, 2.33, 2.85, and 2.6, respectively. CONCLUSION: Herpes simplex-1 and varicella zoster viruses are strongly associated with COVID-19 infection.

Herpes zoster following BNT162b2 mRNA COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series.

OBJECTIVES: As global vaccination campaigns against COVID-19 disease commence, vaccine safety needs to be closely assessed. The safety profile of mRNA-based vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is unknown. The objective of this report is to raise awareness of reactivation of herpes zoster (HZ) following the BNT162b2 mRNA vaccination in patients with AIIRD. METHODS: The safety of the BNT162b2 mRNA vaccination was assessed in an observational study monitoring post-vaccination adverse effects in patients with AIIRD (n = 491) and controls (n = 99), conducted in two rheumatology departments in Israel. RESULTS: The prevalence of HZ was 1.2% (n = 6) in patients with AIIRD compared with none in controls. Six female patients aged 49 ± 11 years with stable AIIRD: RA (n = 4), Sjogren's syndrome (n = 1), and undifferentiated connective disease (n = 1), developed the first in a lifetime event of HZ within a short time after the first vaccine dose in five cases and after the second vaccine dose in one case. In the majority of cases, HZ infection was mild, except a case of HZ ophthalmicus, without corneal involvement, in an RA patient treated with tofacitinib. There were no cases of disseminated HZ disease or postherpetic neuralgia. All but one patient received antiviral treatment with a resolution of HZ-related symptoms up to 6 weeks. Five patients completed the second vaccine dose without other adverse effects. CONCLUSION: Epidemiologic studies on the safety of the mRNA-based COVID-19 vaccines in patients with AIIRD are needed to clarify the association between the BNT162b2 mRNA vaccination and reactivation of zoster.