Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

A roadmap for Antarctic and Southern Ocean science for the next two decades and beyond

Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i)Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access toAntarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.Tinker Foundation, Antarctica New Zealand, The New Zealand Antarctic Research Institute, the Scientific Committee on Antarctic Research (SCAR), the Council of Managers of National Antarctic Programs (COMNAP), the Alfred Wegner Institut, Helmholtz Zentrum für Polar und Meeresforschung (Germany), and the British Antarctic Survey (UK).http://journals.cambridge.org/action/displayJournal?jid=ANShb201

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Leibniz et Christian Knorr von Rosenroth : une amitié méconnue

Leibniz and Christian Knorr von Rosenroth : a little known friendship This article explores the little known friendship between Gottfried Wilhelm Leibniz and Christian Knorr von Rosenroth (1636-1689). Von Rosenroth was one of the foremost Christian Kabbalists of the seventeenth century. He edited the "Kabbala Denudata", the largest collection of kabbalistic texts published in Latin before the nineteenth century. Leibniz visited von Rosenroth in 1688, and stayed with him for more than a month. He refers to von Rosenroth with great admiration in subsequent letters and praises him for his immense knowledge. The article discusses the basis for their friendship and argues that von Rosenroth's kabbalistic ideas influenced Leibniz's concept of monads, his defense of free will, his theodicy and his theory of causality.Le propos de cette étude est d'explorer l'amitié méconnue de Gottfried Wilhelm Leibniz et Christian Knorr von Rosenroth, l'un des plus importants kabbalistes chrétiens du XVIIe siècle. En 1688, Leibniz passa un mois chez von Rosenroth, alors que ce dernier travaillait à la préparation des textes qui devaient par la suite être publiés dans la "Kabbala Denudata" (1677, 1684). Leibniz vouait une grande estime à cet érudit, comme en témoigne sa correspondance. La présente étude traite des fondements de l'amitié entre les deux hommes et montre la façon dont les idées kabbalistiques de von Rosenroth ont influencé Leibniz dans sa conception des monades, son argumentation en faveur du libre arbitre, sa thèodicée et enfin dans sa théorie de la causalité comme volonté.Coudert Allison P. Leibniz et Christian Knorr von Rosenroth : une amitié méconnue. In: Revue de l'histoire des religions, tome 213, n°4, 1996. Langue et Kabbale. pp. 467-484