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.

Full-length IL-33 regulates Smad3 phosphorylation and gene transcription in a distinctive AP2-dependent manner.

IL-33 has emerged as a central mediator of immune, inflammatory, and fibrotic responses. Many studies have focused on mature IL-33, but elevated expression of the precursor, full-length IL-33 (FLIL33), has also been implicated in a spectrum of diseases, including tissue fibrosis. We previously reported and now confirmed that overexpression of FLIL33 induced phosphorylation of the key profibrotic signaling mediator of TGF-ß, Smad3, in primary human lung fibroblasts from healthy donors and idiopathic pulmonary fibrosis patients. Presently, we demonstrate that FLIL33-induced Smad3 phosphorylation was not abrogated by anti-TGF-ß antibody but was abrogated by ALK5/TGFBR1-specific and Smad3-specific inhibition, indicating that FLIL33 effect was independent of TGF-ß but dependent on its receptor, TGFBR. Western blotting analyses revealed that FLIL33 overexpression increased levels, but did not affect subcellular distribution, of the AP2A1 and AP2B1 subunits of the adaptor protein complex 2 (AP2), a known TGFBR binding partner. siRNA-mediated inhibition of these subunits blocked FLIL33-induced Smad3 phosphorylation, whereas AP2 subunit overexpression induced Smad3 phosphorylation even in the absence of FLIL33. RNA-Seq transcriptomic analyses revealed that fibroblast stimulation with TGF-ß induced major changes in expression levels of numerous genes, whereas overexpression of FLIL33 induced modest expression changes in a small number of genes. Furthermore, qRT-PCR tests demonstrated that despite inducing Smad3 phosphorylation, FLIL33 did not induce collagen gene transcription and even mildly attenuated TGF-ß-induced levels of collagen I and III mRNAs. We conclude that FLIL33 induces Smad3 phosphorylation through a TGF-ß-independent but TGF-ß receptor- and AP2- dependent mechanism and has limited downstream transcriptomic consequences.