BackgroundIncreased prevalence of depression has been observed among patients with multiple sclerosis (MS) and correlated with the elevated levels of proinflammatory cytokines and the overall deregulation of monoaminergic neurotransmitters that these patients exhibit. Antidepressants have proved effective not only in treating depression comorbid to MS, but also in alleviating numerous MS symptoms and even minimizing stress-related relapses. Therefore, these agents could prospectively prove beneficial as a complementary MS therapy.ObjectiveThis review aims at illustrating the underlying mechanisms involved in the beneficial clinical effects of antidepressants observed in MS patients.MethodsThrough a literature search we screened and comparatively assessed papers on the effects of antidepressant use both in vitro and in vivo MS models, taking into account a number of inclusion and exclusion criteria.ResultsIn vitro studies indicated that antidepressants promote neural and glial cell viability and differentiation, reduce proinflammatory cytokines and exert neuroprotective activity by eliminating axonal loss. In vivo studies confirmed that antidepressants delayed disease onset and alleviated symptoms in Experimental Autoimmune Encephalomyelitis (EAE), the most prevalent animal model of MS. Further, antidepressant agents suppressed inflammation and restrained demyelination by decreasing immune cell infiltration of the CNS.ConclusionAntidepressants were efficient in tackling numerous aspects of disease pathophysiology both in vitro and in vivo models. Given that several antidepressants have already proved effective in clinical trials on MS patients, the inclusion of such agents in the therapeutic arsenal of MS should be seriously considered, following an individualized approach to minimize the adverse events of antidepressants in MS patients.

This study monitored titers of neutralizing IgG against the receptor-binding domain of the SARS-CoV-2 S1 subunit 14 days post-injection of each dose of the BNT162b2 mRNA Covid-19 vaccine in 401 Greek healthcare workers aged 20–67. After the first dose, titers varied upon age and history of infection, being lower in the 50+ age group and significantly higher among the seropositive. After the second dose, immunogenicity was significantly boosted in the age 50+ and SARS-CoV-2-naïve individuals, indicating the effectuality of its timely administration, yet questioning its value among the seropositive.

Protein replacement therapy is an umbrella term used for medical treatments that aim to substitute or replenish specific protein deficiencies that result either from the protein being absent or non-functional due to mutations in affected patients. Traditionally, such an approach requires a well characterized but arduous and expensive protein production procedure that employs in vitro expression and translation of the pharmaceutical protein in host cells, followed by extensive purification steps. In the wake of the SARS-CoV-2 pandemic, mRNA-based pharmaceuticals were recruited to achieve rapid in vivo production of antigens, proving that the in vivo translation of exogenously administered mRNA is nowadays a viable therapeutic option. In addition, the urgency of the situation and worldwide demand for mRNA-based medicine has led to an evolution in relevant technologies, such as in vitro transcription and nanolipid carriers. In this review, we present preclinical and clinical applications of mRNA as a tool for protein replacement therapy, alongside with information pertaining to the manufacture of modified mRNA through in vitro transcription, carriers employed for its intracellular delivery and critical quality attributes pertaining to the finished product.

Real-world data regarding the effectiveness, safety and immunogenicity of the Pfizer-BioNTech BNT162b2 mRNA vaccine are accumulating in the literature, suggesting that this vaccine generates high titres of S1-binding IgG antibodies that exhibit potent virus neutralization capacity. This is the first phase IV immunogenicity study to recruit a large number of Greek healthcare workers (n=425) including 63 previously-infected subjects. We measured titres of neutralizing IgGs against the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2 14 days post-immunization with the first dose, employing the SARS-CoV-2 IgG II Quant assay. A total of 92.24 % of our study cohort received a positive assay outcome and titres varied with age. Post-hoc analysis revealed that although titres did not significantly differ among participants aged 20–49 years, a significant decline was marked in the age group of 50–59 years, which was further accentuated in subjects aged over 60. Antibody titres escalated significantly among the previously-infected, indicating the potential booster effect of the first dose in that group.