mRNA Vaccine Against COVID-19 May Result in Herpes Zoster Development in Rare Cases

The Pfizer-BioNTech COVID-19 vaccine has, in rare cases, been associated with the development of herpes zoster (HZ), according to a case review published in Rheumatology. The study sample included female patients between 36 and 61 years of age, and in all cases, the baseline rheumatic disease was either mild or stable under medical treatment.

The study reviewed 6 cases of HZ that developed in patients shortly after being vaccinated against COVID-19 with the Pfizer-BioNTech vaccine. In all but 1 patient, the severity of HZ was mild, involving 1 or 2 dermatomes.

The remaining patient developed HZ ophthalmicus without corneal involvement and none of the patients developed disseminated disease or post-herpetic neuralgia. The investigators note that one of the patients developed HZ despite having received an HZ vaccination 2 years prior to the event.

According to the investigators, the close proximity in time between COVID-19 vaccination and the first reactivation of the latent zoster infection raises the possibility of a causal link between the events. Cell-mediated immunity is critical in the prevention of varicella zoster virus (VZV) reactivation; a decline in cell-mediated immunity due to age or disease is associated with a reduction in VZV-specific T cells, which disrupts immune surveillance and increases the risk of reactivation, according to the study authors.

Varicella-like exanthem and HZ have been reported globally in the context of COVID-19 infection since the emergence of the pandemic, with the suggested pathogenetic mechanism relating to the observation that SARS-CoV-2 infection can damage the function of CD4+ T cells and promote excessive activation—and potentially subsequent exhaustion—of CD8+ T cells. These combined disturbances of T cell subsets could eventually diminish host antiviral immunity.

In the context of immunization, the pathogenetic link between mRNA-COVID19 vaccination and HZ reactivation could relate to stimulation of innate immunity through toll-like receptors (TLRs) 3,7 by mRNA-based vaccines. TLR signaling has been implicated in the reaction of herpes viruses, and defects in TLR expression are often observed in patients suffering from diseases caused directly by herpes virus infection. According to the investigators, the vaccine stimulates induction of type I INFs and inflammatory cytokines, which instigate T and B immune responses, but could negatively affect antigen expression, thereby potentially contributing to HZ reactivation.

The investigators stress that causality cannot yet be proved, adding that vigilance and safety monitoring of COVID-19 vaccination adverse effects is warranted based on these data.

REFERENCE

Victoria Furer, Devy Zisman, Adi Kibari, Doron Rimar, Yael Paran, Ori Elkayam; Herpes zoster following BNT162b2 mRNA COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: a case series, Rheumatology, 2021;, keab345, https://doi.org/10.1093/rheumatology/keab345