Background: The role of toll-like receptor 4 (TLR4) in schizophrenia remains unclear, with studies reporting conflicting results on its expression and activation in persons with schizophrenia (PwSCZ). This systematic review/meta-analysis compared basal monocytic TLR4 expression, as well as its activation pattern between PwSCZ and healthy controls (HCs). Methods: This study was registered with PROSPERO (CRD42021273858) and adhered to the PRISMA guidelines. A systematic search was conducted through MEDLINE (via PubMed), Web of Science, and Scopus from inception to December 12, 2023. Quantitative syntheses were conducted for (a) basal monocytic TLR4 density, (b) basal percentage of TLR4⁺ monocytes, and (c) basal TLR4 gene expression. Effect sizes were computed using Hedges’ g for mean differences. Random-effect models with restricted maximum-likelihood estimation were used, and subgrouping was conducted based on antipsychotic status. The studies’ risk of bias was assessed using the Joanna Briggs Institute (JBI) tool. Results: Eleven studies (473 PwSCZ, 416 HCs) were included. Pooled analysis revealed a nonsignificant trend toward increased basal monocytic TLR4 density in PwSCZ (Hedges’ g = 0.317 [95% CI: –0.060, 0.694], τ2 = 0.127, I² = 68.91%). The difference became significant after sensitivity analysis and excluding one study (Hedges’ g = 0.469 [0.195,0.742], p = 0.001). No significant difference was found between the groups in terms of TLR4⁺ monocytes percentage (Hedges’ g = 0.235 [–0.245, 0.715], τ2 = 0.31, I² = 87.30%) or TLR4 gene expression (Hedges’ g = 0.179 [–0.502, 0.861], τ2 = 0.29, I² = 79.04%). According to qualitative synthesis, TLR4 stimulation resulted in reduced monocytic activation in PwSCZ compared to HCs. Conclusions: This study suggested a trend toward an increased basal monocytic TLR4 density in PwSCZ, with no difference in the basal percentage of TLR4⁺ monocytes or TLR4 gene expression. However, the limited available data underscores the need for future studies.

Background and Objective: Bell’s palsy (BP) has been considered as a serious adverse event following the SARS-CoV-2 vaccination. Many studies have reported BP following vaccination, although neither a causative relationship nor a prevalence of the condition higher than the general population has been established. The outcomes of interest were to compare BP incidence among (a) SARS-CoV-2 vaccine recipients, (b) nonrecipients in the placebo or unvaccinated cohorts, (c) different types of SARS-CoV-2 vaccines, and (d) SARS-CoV-2 infected vs. SARS-CoV-2 vaccinated individuals. Methods: We performed a systematic search through MEDLINE (via PubMed), Web of Science, Scopus, Cochrane library, and Google Scholar from the inception to August 15, 2022. We included articles reporting individuals receiving any SARS-CoV-2 vaccine in whom BP had occurred. Studies reporting facial paralysis due to etiologies other than BP were excluded. Random- and fixed-effects meta-analyses using the Mantel-Haenszel method were conducted for the quantitative synthesis. Newcastle-Ottawa scale (NOS) was used to assess the quality. The study was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, and the protocol was registered with PROSPERO (CRD42022313299). Analyses were carried out using the R, version 4.2.1 (R package ‘meta’ version 5.2-0). Results: Fifty studies were included, of which 17 entered the quantitative synthesis. First, pooling four phase-3 randomized controlled trials (RCT) indicated BP occurrence was significantly higher in SARS-CoV-2 vaccines (77, 525 doses) compared to placebo (66, 682 doses) (OR = 3.00, 95% CI = 1.10 - 8.18, I ² = 0%). Second, pooling nine observational studies of mRNA SARS-CoV-2 vaccine doses (13, 518,026) and matched unvaccinated individuals (13, 510,701) revealed no significant increase in the odds of BP in the vaccinated group compared to the unvaccinated group (OR: 0.70 (95% CI 0.42-1.16), I ² =94%). The third meta-analysis suggested that post-vaccination BP among first dose Pfizer/BioNTech recipients (22,760,698) did not significantly differ from that in first dose Oxford/AstraZeneca recipients (22,978,880) (OR = 0.97, 95% CI = 0.82 - 1.15, I ² = 0%). According to the fourth meta-analysis, BP was significantly more commonly reported after SARS-CoV-2 infection (2,641,398) than after SARS-CoV-2 vaccinations (36,988,718) (RR = 4.03, 95% CI = 1.78 - 9.12, I ² = 96%). Conclusion: Our meta-analysis suggests a higher incidence of BP among vaccinated vs. placebo groups. BP occurrence did not significantly differ between Pfizer/BioNTech and Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccines.