ABSTRACT
Background: Although a full course of vaccine against Sars- Cov-2 is effective in most patients with MS (PwMS), the duration of the protection and the efficacy of a booster dose remain poorly explored, especially across different disease modifying treatments (DMTs). Aim(s): To characterize humoral and T-cell immune response along time and following third dose of COVID-19 vaccination in PwMS. Method(s): From an established cohort evaluated at baseline (T0), PwMS were recruited after 24 weeks (T1) from the first cycle of mRNA vaccine and 4 weeks after third dose (T2). At each timepoint we evaluated the serological response by measuring the anti- Region-Binding-Domain (RBD). Cell-mediated response was analyzed by computing interferon (IFN)-gamma in response to spike peptides. Result(s): The baseline cohort consisted of 134 PwMS [mean age 46.6+/-10.8 years;F:92;mean disease duration 15.1+/-9.4 years;26.9% ocrelizumab (OCR) 30.6% fingolimod (FTY), 16.4% cladribine (CLA), 26.1%IFN-s-1a (IFNB)]. Of them, 109 were reassessed at T1, 78 at T2 and 64 completed all evaluations. In the whole cohort there was a significant reduction (p<0.0001) in anti- RBD rate from T0 [76% positive, median 52.8 BAU/ml Interquartile Range (IQR) 1150.9] to T1 (57.8% positive, median 13.2 BAU/ml IQR 95.98] and a significant 20- and 5-fold increase in median titer at T2 (75% positive, median 272.3 BAU/ml IQR 4212.3) from T1 and T0 respectively (p<0.0001). Median IFN-gamma level at T2 was significantly higher than those evaluated at T1 (p<0.0001) and T0 (p=0.009). These latter results were consistent across all DMTs. At T1 the highest detectable anti-RBD response was found in CLA (100%, median 87.7 BAU/ml IQR 22) and IFNB (93.5%;median 126.3 BAU/ml IQR 149.2) cohort, while PwMS treated with FTY and OCR showed 60% (median 8.25 BAU/ml IQR 34.3) and 21% (median 0.8 BAU/ml IQR 6) rate of anti-RBD response respectively. At T2 100% PwMS showed positive anti-RBD response except those treated with OCR (23.8% positive, median 0.6 BAU/ml IQR 4.1). IFN-gamma-S-specific T-cell response was reduced in FTY cohort at both T1 and T2 (3.3 % positive, median 0.8 pg/ml IQR 3.1 and 0.6 pg/ml IQR 2.4 respectively). Conclusion(s): A third dose of COVID-19 vaccine reinforces both humoral and cell-mediated immune response in PwMS on DMTs. Despite vaccination, PwMS treated with OCR and FTY show lower humoral and T-cell specific immune response respectively, suggesting the need of specific treatment to halt COVID-19 in case of infection.
ABSTRACT
Background: Angiotensin-converting enzyme 2 (ACE2) is primarily involved in the ma-turation of angiotensin. It also represents the main receptor for the Severe Acute Respiratory Syn-drome coronavirus 2 (SARS-CoV-2) that caused a serious epidemic COVID-19. Available evi-dence indicates that at the cell membrane, ACE2 can form heteromeric complexes with other mem-brane proteins, including the amino acid transporter B0AT1 and G protein-coupled receptors (G-PCR). Objective: It is well known that during the formation of quaternary structures, the configuration of every single monomer is re-shaped by its interaction pattern in the macromolecular complex. There-fore, it can be hypothesized that the affinity of ACE2 to the viral receptor-binding domain (RBD), when in a heteromeric complex, may depend on the associated partner. Methods: By using established docking and molecular dynamics procedures, the reshaping of monomer was explored in silico to predict possible heterodimeric structures between ACE2 and GPCR, such as angiotensin and bradykinin receptors. The associated possible changes in the bind-ing affinity between the viral RBD and ACE2 when in the heteromeric complexes were also esti-mated. Results and Conclusion: The results provided support to the hypothesis that the heteromerization state of ACE2 may modulate its affinity to the viral RBD. If experimentally confirmed, ACE2 heteromerization may contribute to explain the observed differences in susceptibility to virus infec-tion among individuals and to devise new therapeutic opportunities.
ABSTRACT
Background and aims: In 2018 we surveyed the use of social media and digital devices among Italian neurologists. In the present study, we evaluated whether major changes had occurred in a short time-frame and indirectly assessed the impact of the Sars-COV-2 virus and the related COronaVIrus Disease 19 (COVID-19) pandemic. Methods: Online survey (September 2020 to January 2021) to collect information on attitude toward digital health of members of the Italian Society of Neurology (SIN). The outline of the survey was the same as the prior study. Results: One hundred and nine neurologists participated in the survey. Some major changes were found compared to 2018: fewer participants reported using the tablet (23% versus 43%;p < 0.001) and Facebook (18% versus 32%;p = 0.006) for professional purposes. More participants reported that social media had worsened the doctor-patient relationship, and were against a friendship with their patients in social media. There was a trend towards higher use of WhatsApp (92% versus 82%;p = 0.018), and a significant reduction in active involvement in personal websites, blogs, or online forums. Conclusions: Dramatic changes in the attitudes towards social media have occurred in Italy in a very short timeframe, probably due to the concurrent pandemic and its impact on daily practice, and the dissemination of online misinformation.