Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination.

BACKGROUND: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear. OBJECTIVE: To report COVID-19 rates in pwMS according to vaccine serology. METHODS: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included. Logistic regression was performed to examine whether seroconversion following vaccination predicted risk of subsequent COVID-19 infection after adjusting for potential confounders. Rates of severe COVID-19 (requiring hospitalisation) were also calculated. RESULTS: A total of 647 pwMS were included (mean age 48 years, 500 (77%) female, median Expanded Disability Status Scale (EDSS) 3.5% and 524 (81%) exposed to DMT at the time of vaccine 1). Overall, 472 out of 588 (73%) were seropositive after vaccines 1 and 2 and 222 out of 305 (73%) after vaccine 3. Seronegative status after vaccine 2 was associated with significantly higher odds of subsequent COVID-19 infection (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.34-4.12, p = 0.0029), whereas seronegative status after vaccine 3 was not (OR: 1.05, 95% CI: 0.57-1.91). Five people (0.8%) experienced severe COVID-19, all of whom were seronegative after most recent vaccination. CONCLUSION: Attenuated humoral response to initial COVID-19 vaccination predicts increased risk of COVID-19 in pwMS, but overall low rates of severe COVID-19 were seen.

Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis.

BACKGROUND: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group. METHODS: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. RESULTS: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There was no association between laboratory evidence of prior COVID-19 and seroconversion following vaccine 3. CONCLUSIONS: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

The Increased Densities, But Different Distributions, of Both C3 and S100A10 Immunopositive Astrocyte-Like Cells in Alzheimer's Disease Brains Suggest Possible Roles for Both A1 and A2 Astrocytes in the Disease Pathogenesis.

There is increasing evidence of astrocyte dysfunction in the pathogenesis of Alzheimer's disease (AD). Animal studies supported by human post-mortem work have demonstrated two main astrocyte types: the C3 immunopositive neurotoxic A1 astrocytes and the S100A10 immunopositive neuroprotective A2 astrocytes. A1 astrocytes predominate in AD, but the number of cases has been relatively small. We examined post-mortem brains from a larger cohort of AD cases and controls employing C3 and S100 immunohistochemistry to identify the astrocytic subtypes. There were a number of C3 immunopositive astrocyte-like cells (ASLCs) in the control cases, especially in the lower cerebral cortex and white matter. In AD this cell density appeared to be increased in the upper cerebral cortex but was similar to controls in other regions. The S100A10 showed minimal immunopositivity in the control cases in the cortex and white matter, but there was increased ASLC density in upper/lower cortex and white matter in AD compared to controls. In AD and control cases the numbers of C3 immunopositive ASLCs were greater than those for S100A10 ASLCs in all areas studied. It would appear that the relationship between A1 and A2 astrocytes and their possible role in the pathogenesis of AD is complex and requires more research.

Effects of imidacloprid on Rana catesbeiana immune and nervous system.

Imidacloprid (IMD), a neonicotinoid, is generally considered to be of low toxicity in vertebrates. However, the inhibition of acetylcholine (ACh) receptors can have a profound effect on both the immune and nervous system due to the anti-inflammatory effects of ACh. Vertebrates, such as amphibians, might be affected by IMD because they breed in wetlands where the concentration of IMD is high. In our study, we experimentally exposed Rana catesbeiana tadpoles to environmentally relevant IMD and then quantified the ACh and antibody to non-replicating antigens. We hypothesized that IMD exposure would result in higher AChE and antibody levels. We completed a factorial experiment in which tadpoles were divided into four groups, two of which were exposed to 100 ng/L of IMD. After five weeks, two groups were injected with the novel antigen keyhole limpet hemocyanin (KLH) and two injected with a control. Three weeks later, tadpoles were euthanized and blood samples collected. At 100 ng/L, IMD exposure did not cause a significant difference in AChE levels or KLH-specific IgY antibodies. However, tadpoles injected with KLH had slightly higher levels of AChE. In addition, we saw a trend in total IgM with higher levels in tadpoles exposed to IMD. While we found no effect of IMD at 100 ng/L on antibody response to a novel, non-replicating antigen nor on ACh production, further research is needed to determine if higher concentrations of IMD or parasite infection can influence development of R. catesbeiana.