Can SARS-CoV-2 vaccine increase the risk of reactivation of Varicella zoster? A systematic review.

INTRODUCTION: Although the COVID-19 vaccination is deemed safe, exact incidence and nature if adverse effects, particularly dermatological ones, are still unknown. OBJECTIVE: To describe the demographic, clinical, morphological characteristics, outcomes, and timing of development of herpes zoster to the various COVID-19 vaccines. And to identify on whether COVID-19 vaccine has temporal relationship between development of herpes zoster (HZ). METHODS: We have performed a systemic review of articles from PubMed and Embase using MeSH and keywords like "Shingles," "Herpes zoster," "Varicella zoster," "COVID-19," "Vaccine," "SARS-CoV-2." No filters including country of publication, language, type of articles were applied. Individual case report references were filtered for any pertinent cases. RESULTS: A total of 54 cases consisting of 27 male and 27 female patients have been reported. There were cases with known risk factors for herpes zoster, which included age more than 50 years (n = 36), immunological disorders (n = 10), chronic disease (n = 25), metabolic disorder (n = 13), malignancy (n = 4), and psychiatric disorder (n = 2). The mean (SD) period between development of herpes zoster and COVID-19 vaccination was 7.64 (6.92) days. Majority of the cases were from the high-income and/or middle-income countries. 86.27% of the cases of HZ were reported due to mRNA vaccine. Thirty-six patients 36/45 (80%) developed herpes zoster following the priming dose of COVID-19 vaccine among those who received mRNA vaccine. CONCLUSION: We could not establish definite link but there may be possible association between COVID-19 vaccine and shingles. Large-scale studies may help to understand the cause-effect relationship.

Synthesis of the Data on COVID-19 Skin Manifestations: Underlying Mechanisms and Potential Outcomes.

The incidence of coronavirus disease 2019 (COVID-19)-related skin manifestations has progressively grown, in parallel with the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading. The available evidence indicates that cutaneous signs are heterogeneous and can be divided as follows: a) erythematous rashes, b) lesions of vascular origin, c) vesicular rashes, d) urticarial rashes, and e) acute generalized exanthematous pustulosis (AGEP), erythema multiforme (EM) and other polymorphic/atypical reactions. Most cutaneous manifestations appear simultaneously or after respiratory and/or systemic symptoms such as fever, even if rarely urticaria has been reported as the first sign of the disease. It has been proposed that erythematous and vesicular rashes, as well as urticaria, are the result of immunological activation against Sars-CoV-2, similarly to other viral exanthems; alternatively, reactivation or co-infection of herpesviruses and drug hypersensitivity represent possible etiologic diagnosis that has to be considered. Regarding lesions of vascular origin, ischemic ones are the result of systemic hypercoagulability established in severe infections, whereas chilblains seem to be linked to the type I-interferon massively produced to halt virus replication. AGEP is triggered by drugs, whereas EM could represent a delayed immune response to the virus or a hypersensitivity reaction to drugs elicited by the inflammatory process built to fight the infection. A further pathogenic hypothesis is that the virus, or its particles detected in the skin (particularly in endothelium and eccrine glands), could be responsible for certain skin reactions, including chilblains and EM. From the available data, it appears that chilblains are correlated with younger age and less severe disease, while ischemic manifestations occur in the elderly with severe infection. In conclusion, larger studies are needed to confirm the suggested pathogenetic mechanisms of COVID-19-related skin reactions and to determine the potential prognostic significance of each one.

Systemic immunosuppression in times of COVID-19: Do we need to rethink our standards?

The current SARS-CoV-2 pandemic particularly endangers older people with pre-existing cardiopulmonary and metabolic conditions. However, it is also currently under discussion whether patients under immunosuppressive therapy also have a higher risk of suffering a severe course of the COVID-19 disease. In principle though, there is currently no data available for a general reduction or pause of immunosuppression in patients with autoimmune diseases because of the SARS-CoV-2 pandemic. However, since there is currently neither an effective therapy nor corresponding vaccination protection, the indication for a prolonged immunosuppressive therapy should be made with special care. In particular, immunotherapeutic agents that produce long-term effects (e.g., rituximab) should be used with special caution. In contrast, immunomodulating substances that do not suppress antiviral immunity (e.g. systemic immunoglobulins, doxycycline), or that have intrinsic effects on SARS-CoV-2 (calcineurin inhibitors, chloroquine, hydroxychloroquine) may be useful alternatives.