SARS-CoV-2 Vaccination Responses in Anti-CD20-Treated Progressive Multiple Sclerosis Patients Show Immunosenescence in Antigen-Specific B and T Cells.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are largely used in the treatment of both relapsing remitting (RR) and progressive (PR) forms of MS. Although effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and a high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality; this, however, suggested the presence of differences in immune responses driven by age and disease severity.

Kappa index in the diagnostic work-up of autoimmune encephalitis.

BACKGROUND: The presence of inflammatory changes in the cerebrospinal fluid (CSF), including immunoglobulin intrathecal synthesis (IS), can support the diagnosis of autoimmune encephalitis (AE) and allow prompt treatment. The main aim of our study was to calculate the Kappa index as a marker of IS, in patients with AE. METHODS: Charts of patients undergoing a diagnostic work-up for suspected AE between 2009 and 2023 were reviewed and the Graus criteria applied. CSF and serum kappa free light chains were determined using the Freelite assay (The Binding Site Group) and the turbidimetric Optilite analyzer. RESULTS: We identified 34 patients with "definite" AE (9 anti-NMDAR AE and 25 limbic AE) and nine patients with "possible" AE. Five patients (15%) with definite AE had pleocytosis and twelve (34%) showed CSF-restricted oligoclonal bands (OCB) at isoelectric focusing. The Kappa index was >6 in 29.4% and > 3 in 50% of the definite AE patients. It was elevated (>3) in 36.4% of patients with definite AE who resulted negative to OCB testing and was the only altered parameter suggestive of an ongoing inflammatory process in the CNS in three definite AE patients with otherwise normal CSF findings (i.e. normal cell count and protein levels, no OCBs). In the possible AE group, one patient had a Kappa index >3 in the absence of OCB. CONCLUSIONS: The Kappa index could be useful, as a more sensitive marker of IS and as a supportive marker of neuroinflammation, in the diagnostic work-up of suspected AE.

Immunosenescence and vaccine efficacy revealed by immunometabolic analysis of SARS-CoV-2-specific cells in multiple sclerosis patients.

Disease-modifying therapies (DMT) administered to patients with multiple sclerosis (MS) can influence immune responses to SARS-CoV-2 and vaccine efficacy. However, data on the detailed phenotypic, functional and metabolic characteristics of antigen (Ag)-specific cells following the third dose of mRNA vaccine remain scarce. Here, using flow cytometry and 45-parameter mass cytometry, we broadly investigate the phenotype, function and the single-cell metabolic profile of SARS-CoV-2-specific T and B cells up to 8 months after the third dose of mRNA vaccine in a cohort of 94 patients with MS treated with different DMT, including cladribine, dimethyl fumarate, fingolimod, interferon, natalizumab, teriflunomide, rituximab or ocrelizumab. Almost all patients display functional immune response to SARS-CoV-2. Different metabolic profiles characterize antigen-specific-T and -B cell response in fingolimod- and natalizumab-treated patients, whose immune response differs from all the other MS treatments.

Will the COVID-19 pandemic transform infection prevention and control in surgery? Seeking leverage points for organizational learning.

BACKGROUND: In response to the coronavirus disease of 2019 (COVID-19) pandemic, healthcare systems worldwide have stepped up their infection prevention and control efforts in order to reduce the spread of the infection. Behaviours, such as hand hygiene, screening and cohorting of patients, and the appropriate use of antibiotics have long been recommended in surgery, but their implementation has often been patchy. METHODS: The current crisis presents an opportunity to learn about how to improve infection prevention and control and surveillance (IPCS) behaviours. The improvements made were mainly informal, quick and stemming from the frontline rather than originating from formal organizational structures. The adaptations made and the expertise acquired have the potential for triggering deeper learning and to create enduring improvements in the routine identification and management of infections relating to surgery. RESULTS: This paper aims to illustrate how adopting a human factors and ergonomics perspective can provide insights into how clinical work systems have been adapted and reconfigured in order to keep patients and staff safe. CONCLUSION: For achieving sustainable change in IPCS practices in surgery during COVID-19 and beyond we need to enhance organizational learning potentials.

SARS-CoV-2 pandemic: implications in the management of patients with colorectal cancer.

The SARS-CoV-2 pandemic has already reached 3,207,248 patients with more than 225,000 deaths all over the world. Colorectal cancer is the third most diagnosed cancer worldwide, and the healthcare system is struggling to manage daily activities for elective cancer surgery. This review integrates clinical, microbiological, architectural and surgical aspects to develop indications on strategies to manage colorectal cancer patients and ensure safety during the pandemic. Telephone or virtual clinics must be encouraged and phone follow-up should be implemented. Indications for surgery must be rigorous, balancing the advantage of early surgical treatment and risks of treatment delay. To decrease the occupancy rate of intensive care unit beds, elective surgical treatment should be delayed until local endemic control, according to stage of disease. Patients with SARS-CoV-2 infection should be treated only after clinical recovery, two consecutive negative oropharyngeal swabs and, if available, a negative stool sample. Before any elective oncologic procedure, a multidisciplinary oncologic team including an anaesthesiologist and an infectious disease specialist must assess every patient to evaluate the risk of infection and its impact on perioperative morbidity, mortality and oncologic prognosis. The hospital should organise to manage all elective oncologic patients in an 'infection-free' area or refer them to a non-SARS-CoV-2 hospital.