SARS-CoV-2 mRNA vaccination induces stem cell memory T cells specific for the virus that persist up to 6 months.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a chronic inflammatory disease associated with frustrating symptoms, particularly nasal obstruction and loss of smell. We conducted a patient survey on the significant burden of the disease, with a specific focus on conditions that affect health, sleep quality, absenteeism, and presenteeism, including the caregivers’ perspectives. Methods: An online questionnaire was sent to 4230 randomly selected recipients, and 200 matched the inclusion criteria for self-reported CRSwNPs symptoms. A total of 100 participants not matching the inclusion criteria for CRSwNPs were recruited as a control group. The study also collected the perspectives of 50 caregivers. Results: Patients with CRSwNPs experienced very bothersome symptoms, such as nasal congestion, headache, and rhinorrhoea, with a profound impact on their health-related quality of life (HRQoL). The patients and their caregivers showed significantly lower quality of sleep, experiencing a poor night’s sleep on average 72.1 and 51.7 days per year, respectively. Smell and taste impairments significantly impacted patients’ social and working lives, with 39.5% feeling in danger because of hyposmia and 34.5% because of limited taste. Out-of-pocket costs were up to EUR 40/month for 68.5% of patients. CRSwNPs alone was responsible for an average of 24.7 days of absenteeism and 25.1 days of presenteeism. Conclusions: Our results highlight how CRSwNPs has a negative impact on patients’ and caregivers’ HRQoL. Most bothersome and health-conditioning symptoms involve nose symptoms and poor sleep quality, resulting in patient absenteeism and presenteeism with a strong burden on cognitive and emotional functioning for both patients and their caregivers.

Importance: The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from convalescent or vaccinated individuals imposes the study of cellular immunity to predict the degree of immune protection to the yet again new coronavirus. Design: Prospective monocentric observational study. Setting: Conducted between December 20-21 at the Santa Lucia Foundation IRCCS. Participants: 61 volunteers (Mean age 41.62, range 21-62; 38F/23M) with different vaccination and SARS-CoV-2 infection backgrounds donated 15 ml of blood. Of these donors, one had recently completed chemotherapy, and one was undergoing treatment with monoclonal antibodies; the others reported no known health issue. Main Outcome(s) and Measure(s): The outcomes were the measurement of T cell reactivity to the mutated regions of the Spike protein of the Omicron SARS-CoV-2 variant and the assessment of remaining T cell immunity to the spike protein by stimulation with peptide libraries. Results: Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the Spike protein of SARS-CoV-2. T cell responses to peptides covering the mutated regions in the Omicron variant were decreased by over 47% compared to the same regions of the ancestral vaccine strain. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 83%). No significant differences in loss of immune recognition were identified between groups of donors with different vaccination and/or infection histories. Conclusions and Relevance: We conclude that despite the mutations in the Spike protein, the SARS-CoV-2 Omicron variant is nonetheless recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease is maintained. Key Points: Question: Does the Omicron variant of SARS-CoV-2 escape cellular immunity? Findings: This observational study was performed on 61 vaccinated donors with established immunity to SARS-CoV-2. Cellular responses to the mutated regions of the Omicron Spike protein were detected in 80% of donors. The mutations reduced T cell recognition by 47% compared to the vaccine strain. Reactivity to the whole Spike protein, however, was present in 100% of donors, and the fraction of remaining immunity to SARS-CoV-2 was estimated to be 83%. Meaning: Cellular immunity to the Omicron variant is maintained despite the mutations in its Spike protein, and may thus confer protection from severe COVID-19 in vaccinated individuals.

Breakthrough infections in SARS-CoV-2 vaccinated individuals are an ideal circumstance for the simultaneous exploration of both the vaccine-induced memory reaction to the spike (S) protein and the primary response to the membrane (M) and nucleocapsid (N) proteins generated by natural infection. We monitored 15 healthcare workers who had been vaccinated with two doses of Pfizer BioNTech BNT162b2 and were then later infected with the SARS-CoV-2 B.1.617.2. (Delta) variant, analysing the antiviral humoral and cellular immune responses. Natural infection determined an immediate and sharp rise in anti-RBD antibody titres and in the frequency of both S-specific antibody secreting cells (ASCs) and memory B lymphocytes. T cells responded promptly to infection by activating and expanding already at 2–5 days. S-specific memory and emerging M- and N-specific T cells both expressed high levels of activation markers and showed effector capacity with similar kinetics but with different magnitude. The results show that natural infection with SARS-CoV-2 in vaccinated individuals induces fully functional and rapidly expanding T and B lymphocytes in concert with the emergence of novel virus-specific T cells. This swift and punctual response also covers viral variants and captures a paradigmatic case of a healthy adaptive immune reaction to infection with a mutating virus.

Atypical B cells (ABCs) are observed across infections, yet their ontogeny and differentiation remain unclear. Using high-dimensional flow cytometry, single-cell transcriptomics, V(D)J sequencing, and functional assays in human malaria and healthy donors, we identified markers of cellular origin while tracking ABC differentiation. Early ABCs express CD11c and arise predominantly from memory B cells. Two intermediate states originate from germinal center-derived and marginal zone-like B cells. Pseudotime and lineage analyses reveal trajectories marked by progressive CD24 and CD27 loss, recapitulated in vitro, defining bona fide differentiation programs. Differentiation culminates in late ABCs lacking CD24, CD27, and CD21, with high CD11c, T-bet, and NKG7, partly overlapping with double-negative 2 cells. Early- and intermediate stages show greater plasma-cell differentiation potential and cytokine production capacity, whereas later stages acquire antigen-presentation transcriptomic signatures and microbial-particle association, defining stage-dependent functions that reconcile conflicting ABC roles. Comparable ABC populations occur in healthy blood and tonsils, with tissue-associated class switching and CD86 expression consistent with recent T-cell interaction. This framework consolidates ABC definitions onto a single differentiation axis and clarifies cellular origins. Graphical

Objective: Multiple sclerosis (MS) is a chronic autoimmune disease where B cells play a central pathogenic role. Cladribine, an oral therapy, provides durable benefits by reshaping lymphocyte populations, yet its specific long‐term impact on distinct B‐cell subsets is not fully understood. This study aimed to define cladribine's longitudinal effects on B‐cell subsets and characterize their inflammatory properties. Methods: We conducted a 48‐month longitudinal study of 36 persons with relapsing–remitting MS treated with cladribine who had completed 2 annual treatment cycles, using high‐parameter flow cytometry to track B‐cell subset dynamics. In a parallel cross‐sectional analysis, B cells from 16 untreated patients and 16 healthy donors were profiled for polyfunctional cytokine production granulocyte‐macrophage colony stimulating factor (GM‐CSF), interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α) and key surface markers. Results: Cladribine induced profound, sustained depletion of memory B cells, with marginal zone‐like (MZ‐like) cells showing the deepest and most persistent loss, alongside reconstitution of transitional and naïve populations. Functionally, MZ‐like B cells were the most potent polyfunctional producers of proinflammatory cytokines and immunoglobulin M (IgM), a capacity significantly enhanced in persons with MS compared to healthy donors, and expressed the highest levels of CD1c and CD1d, consistent with specialization in lipid antigen presentation. Interpretation: MZ‐like B cells are a dominant, polyfunctional inflammatory subset in MS, equipped for non‐canonical lipid antigen presentation and IgM secretion. They represent a preferential pharmacological target of cladribine. Sustained reduction of this pathogenic memory pool, followed by repopulation with less inflammatory B cells, offers a mechanistic basis for cladribine's durable clinical benefit and nominates MZ‐like cells as biomarkers of response and therapeutic targets. ANN NEUROL 2026