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Introduction: COVID-19 vaccines are expected to provide effective protection. However, emerging strains can cause breakthrough infection in vaccinated individuals. The immune response of vaccinated individuals who have experienced breakthrough infection is still poorly understood., Methods: Here, we studied the humoral and cellular immune responses of fully vaccinated individuals who subsequently experienced breakthrough infection due to the Delta variant of SARS-CoV-2 and correlated them with the severity of the disease., Results: In this study, an effective humoral response alone was not sufficient to induce effective immune protection against severe breakthrough infection, which also required effective cell-mediated immunity to SARS-CoV-2. Patients who did not require oxygen had significantly higher specific (p=0.021) and nonspecific (p=0.004) cellular responses to SARS-CoV-2 at the onset of infection than those who progressed to a severe form., Discussion: Knowing both humoral and cellular immune response could allow to adapt preventive strategy, by better selecting patients who would benefit from additional vaccine boosters., Trial Registration Numbers: https://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Buscot, Cremoni, Graça, Brglez, Courjon, Allouche, Teisseyre, Boyer, Barrière, Chamorey, Carles and Seitz-Polski.)

Introduction: Data on immune response to SARS-CoV-2 vaccine in patients living with HIV (PLWH) over a period longer than 3 months are currently limited. We measured the immune response after BNT162b2 vaccination against SARS-CoV-2 in this population., Methods: We prospectively enrolled PLWH on successful antiretroviral therapy, initiating vaccination with two doses of the BNT162b2 SARS-CoV-2 vaccine administered at six-week interval. SARS-CoV-2 humoral and cellular responses and lymphocyte cell subsets were recorded at inclusion and 6 weeks (W6), 3 months (M3) and 6 months (M6) later. Humoral, humoral strong and cellular responders were defined by IgG titers >10, ≥264BAU/mL and IFN-γ T cell release, respectively., Results: Nineteen subjects without SARS-CoV-2 infection were included (74% men, mean age 51 years, CD4 nadir 399/mm3). All subjects were humoral responders, their antibody titer peak reached at M3. Strong responders' rates were 63% and 21% at M3 and M6, respectively. CD19+CD10+ B cells had increased significantly at W6 then decreased at M3, while CD19+CD27+ B cells remained unchanged. Rates of patients with a cellular response increased from 39% at W6 to 69% at M6. Cellular responders had significantly higher CD3+, CD4+ and CD8+ Effector Memory cells at inclusion (p=0.048, p=0.024, p=0.012, respectively) and CD4+ Terminally Differentiated Effector Memory cells at M3 (p=0.044)., Discussion: PLWH have a robust immune response after SARS-CoV-2 vaccination, but a rapid decline in humoral response from 3 months onwards, due to a blunted memory B cell response. Analysis of lymphocyte subsets may help identify optimal times for vaccine boosters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Manni, Ruetsch, Fabre, Ticchioni, Graça, Pradier, Seitz-Polski, Lotte, Brglez and Vassallo.)

The SARS-CoV-2 infection has spread rapidly around the world causing millions of deaths. Several treatments can reduce mortality and hospitalization. However, their efficacy depends on the choice of the molecule and the precise timing of its administration to ensure viral clearance and avoid a deleterious inflammatory response. Here, we investigated IFN-γ, assessed by a functional immunoassay, as a predictive biomarker for the risk of hospitalization at an early stage of infection or within one month prior to infection. Individuals with IFN-γ levels below 15 IU/mL were 6.57-times more likely to be hospitalized than those with higher values (p<0.001). As confirmed by multivariable analysis, low IFN-γ levels, age >65 years, and no vaccination were independently associated with hospitalization. In addition, we found a significant inverse correlation between low IFN-γ response and high level of IL-6 in plasma (Spearman's rho=-0.38, p=0.003). Early analysis of the IFN-γ response in a contact or recently infected subject with SARS-CoV-2 could predict hospitalization and thus help the clinician to choose the appropriate treatment avoiding severe forms of infection and hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cremoni, Allouche, Graça, Zorzi, Fernandez, Teisseyre, Benzaken, Ruetsch-Chelli, Esnault, Dellamonica, Carles, Barrière, Ticchioni, Brglez and Seitz-Polski.)

Primary membranous nephropathy (pMN) is an auto-immune disease characterized by auto-antibodies targeting podocyte antigens resulting in activation of complement and damage to the glomerular basement membrane. pMN is the most common cause of nephrotic syndrome in adults without diabetes. Despite a very heterogeneous course of the disease, the treatment of pMN has for many years been based on uniform management of all patients regardless of the severity of the disease. The identification of prognostic markers has radically changed the vision of pMN and allowed KDIGO guidelines to evolve in 2021 towards a more personalized management based on the assessment of the risk of progressive loss of kidney function. The recognition of pMN as an antibody-mediated autoimmune disease has rationalized the use immunosuppressive drugs such as rituximab. Rituximab is now a first line immunosuppressive therapy for patients with pMN with proven safety and efficacy achieving remission in 60-80% of patients. For the remaining 20-40% of patients, several mechanisms may explain rituximab resistance: (i) decreased rituximab bioavailability; (ii) immunization against rituximab; and (iii) chronic glomerular damage. The treatment of patients with rituximab-refractory pMN remains controversial and challenging. In this review, we provide an overview of recent advances in the management of pMN (according to the KDIGO 2021 guidelines), in the understanding of the pathophysiology of rituximab resistance, and in the management of rituximab-refractory pMN. We propose a treatment decision aid based on immunomonitoring to identify failures related to underdosing or immunization against rituximab to overcome treatment resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Teisseyre, Cremoni, Boyer-Suavet, Ruetsch, Graça, Esnault, Brglez and Seitz-Polski.)