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Between March 2021 and February 2022, SARS-CoV-2 neutralizing antibodies dynamics was investigated in a prospective observational study in 903 healthcare workers of a hospital in Switzerland. A surrogate neutralization assay measuring the competitive inhibition of the angiotensin converting enzyme 2 (ACE2) binding to the spike protein (S) of the SARS-CoV-2 wild type virus and to five variants of concern (Alpha, Beta, Gamma, Delta, Omicron) was used. We observed a broad distribution of neutralization activity among participants and substantial differences in neutralizing titers against variants. Participants were grouped based on combinations of vaccination status (1, 2 or 3 doses) and/or prior or subsequent SARS-CoV-2 infection/reinfection. Triple vaccination resulted in the highest neutralization response, as did double vaccination with prior or subsequent infection. Double vaccination without infection showed an intermediate neutralization response while SARS-CoV-2 infection in non-vaccinated participants resulted in poor neutralization response. After triple vaccination or double vaccination plus infection, additional vaccination and/or reinfection had no impact on neutralizing antibody titers over the observed period. These results strongly support the booster dose strategy, while additional booster doses within short time intervals might not improve immunization. However, dynamics of neutralizing antibodies titers needs to be monitored individually, over time and include newly emerging variants., Competing Interests: Declaration of competing interest G. Greub is medical advisor of Resistell, a startup active in the development of a new instrument to faster antibiotic susceptibility results. G. Greub has a research agreement with Becton Dickinson (USA) and Resistell (Switzerland), both unrelated to the present work. The rest of the authors have no conflict of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: For patients with corticosteroid (CS)-refractory immune checkpoint inhibitor-related cholangiohepatitis (irCH), no consensus exists regarding treatment, and outcomes remain poor. We evaluated the possibility of personalized treatment according to the patient's cytokine profile and the immunohistopathologic assessment of the predominant immune infiltrate type of liver tissue., Methods: NSCLCs with CS-refractory irCH were analyzed by immunohistochemistry of liver biopsy specimen, serum cytokine panel, and assessment of peripheral blood mononuclear cell immune cell monitoring by mass cytometry., Results: A total of three consecutive patients with irCH were identified. We found a predominant T-cell infiltrate and an interferon-gamma or T helper 1 proinflammatory cytokine profile. Here, we report for the first time that a T-cell-targeted therapy with the interleukin (IL)-6 receptor-neutralizing antibody tocilizumab, which inhibits signaling downstream of interferon-gamma and several other Janus kinase-dependent cytokines, is an effective single cytokine-directed therapy for CS-refractory irCH. Three patients with severe, CS-refractory irCH who were treated with tocilizumab were found to have persistent clinical and biological remission., Conclusions: Dysregulation of the IL-6/T-cell axis may contribute to the pathogenesis of CS-refractory irCH. Our observations suggest that IL-6 blockade seems to have promise in the treatment of CS-refractory irCH. The results from our three patients need to be confirmed in a larger patient population., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The capacity of the HIV-1 envelope glycoprotein gp120 to induce intracellular signals is thought to contribute to HIV-1 pathogenesis. Here, we report that gp120 binding resulted in activation of the mitogen-activated protein kinase (MAPK) in CD4(+) lymphocytes prestimulated through their T-cell receptor (TCR). However, gp120 did not activate this pathway in either freshly isolated quiescent T cells or nonproliferating CD4(+) lymphocytes prestimulated with the interleukin-7 (IL-7) cytokine. This response was not solely dependent on proliferation per se because proliferating IL-7-prestimulated umbilical cord (UC)-derived T lymphocytes did not exhibit significant MAPK activation upon gp120 binding. Nevertheless, like peripheral blood lymphocytes, MAPK recruitment was induced by gp120 in UC T cells following TCR prestimulation. The lack of a gp120-mediated signaling response was not due to decreased gp120 receptor levels; CD4 expression was modified neither by IL-7 nor by TCR engagement, and high levels of functional CXCR4 were present on IL-7-treated lymphocytes. In addition to CD4 and CXCR4, recent evidence suggests that glycosphingolipids in raft microdomains serve as cofactors for HIV-1 fusion. The ganglioside GM1, a marker of rafts, was augmented in TCR-stimulated but not IL-7-stimulated T lymphocytes, and disruption of rafts inhibited gp120-induced signaling. Thus, stimulation of a mitogenic pathway by gp120 appears to require receptor binding in the context of membrane microdomains. These studies reveal a mechanism via which gp120 may differentially modulate the fate of activated and quiescent T cells in vivo.

"Interplanetary Dust Particles" with sizes approximately 10 micrometers collected in the stratosphere (IDPs), as well as much larger "giant" micrometeorites retrieved from Antarctic ice melt water (AMMs), are mostly composed of unequilibrated assemblages of minerals, thus being related to primitive unequilibrated meteorites. Two independent evaluations of the mass flux of micrometeorites measuring approximately 50 micrometers to approximately 200 micrometers, recovered from either the Greenland or the Antarctic ice sheets have been reported (approximately 20,000 tons/a). A comparison with recent evaluation of the flux of meteorites reaching the Earth's surface (up to masses of 10,000 tons), indicates that micrometeorites represent about 99.5% of the extraterrestrial material falling on the Earth's surface each year. As they show carbon concentrations exceeding that of the most C-rich meteorite (Orgueil), they are the major contributors of extraterrestrial C-rich matter accreting to the Earth today. Moreover they are complex microstructured aggregates of grains. They contain not only a variety of C-rich matter, such as a new "dirty" magnetite phase enriched in P, S, and minor elements, but also a diversity of potential catalysts (hydrous silicates, oxides, sulfides and metal grains of Fe/Ni composition, etc.). They could have individually functioned on the early Earth, as "micro-chondritic-reactors" for the processing of prebiotic organic molecules in liquid water. Future progress requires the challenging development of meaningful laboratory simulation experiments, and a better understanding of the partial reprocessing of micrometeorites in the atmosphere.