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CD8+ T cells are critical for immune protection against severe COVID-19 during acute infection with SARS-CoV-2. However, the induction of antiviral CD8+ T cell responses varies substantially among infected people, and a better understanding of the mechanisms that underlie such immune heterogeneity is required for pandemic preparedness and risk stratification. In this study, we analyzed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in relation to age, clinical status, and inflammation among patients infected primarily during the initial wave of the pandemic in France or Japan. We found that age-related contraction of the naive lymphocyte pool and systemic inflammation were associated with suboptimal SARS-CoV-2-specific CD4+ and, even more evidently, CD8+ T cell immunity in patients with acute COVID-19. No such differences were observed for humoral immune responses targeting the spike protein of SARS-CoV-2. We also found that the proinflammatory cytokine IL-18, concentrations of which were significantly elevated among patients with severe disease, suppressed the de novo induction and memory recall of antigen-specific CD8+ T cells, including those directed against SARS-CoV-2. These results potentially explain the vulnerability of older adults to infections that elicit a profound inflammatory response, exemplified by acute COVID-19.

Adenoviral and mRNA vaccines encoding the viral spike (S) protein have been deployed globally to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older individuals are particularly vulnerable to severe infection, probably reflecting age-related changes in the immune system, which can also compromise vaccine efficacy. It is nonetheless unclear to what extent different vaccine platforms are impacted by immunosenescence. Here, we evaluated S protein-specific immune responses elicited by vaccination with two doses of BNT162b2 or ChAdOx1-S and subsequently boosted with a single dose of BNT162b2 or mRNA-1273, comparing age-stratified participants with no evidence of previous infection with SARS-CoV-2. We found that aging profoundly compromised S protein-specific IgG titers and further limited S protein-specific CD4 + and CD8 + T cell immunity as a probable function of progressive erosion of the naive lymphocyte pool in individuals vaccinated initially with BNT162b2. Our results demonstrate that primary vaccination with ChAdOx1-S and subsequent boosting with BNT162b2 or mRNA-1273 promotes sustained immunological memory in older adults and potentially confers optimal protection against coronavirus disease 2019., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The mucosal immune response is recognized to be important in the early control of infection sustained by viruses with mucosal tissues as the primary site of entry and replication, such as SARS-CoV-2. Mucosal IgA has been consistently reported in the mouth and eye of SARS-CoV-2 infected subjects, where it correlated inversely with COVID-19 symptom severity. Yet, there is still scarce information on the comparative ability of the diverse SARS-CoV-2 vaccines to induce local IgA responses at the virus entry site. Thus, the aim of this study was to assess the presence of anti-SARS-CoV-2 IgA in the saliva of 95 subjects vaccinated with a booster dose and different combinations of vaccines, including mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech), and Vaxzevria (AstraZeneca). The results showed the presence of a mucosal response in 93.7% of vaccinated subjects, with a mean IgA titer of 351.5 ± 31.77 U/mL, strongly correlating with the serum anti-SARS-CoV-2 IgG titer ( p < 0.0001). No statistically significant differences emerged between the vaccine types, although the salivary IgA titer appeared slightly higher after receiving a booster dose of the mRNA-1273 vaccine (Moderna) following two doses of BNT162b2 (Pfizer-BioNTech), compared to the other vaccine combinations. These data confirm what was previously reported at the eye level and suggest that monitoring salivary IgA may be a useful tool for driving forward vaccine design and surveillance strategies, potentially leading to novel routes of vaccine administration and boosting.

Advanced age is associated with severe symptoms and death upon SARS-CoV-2 infection. Virus-specific CD8 + T-cell responses have shown to be protective toward critical COVID-19 manifestations, suggesting that suboptimal cellular immunity may contribute to the age-pattern of the disease. The induction of a CD8 + T-cell response against an emerging pathogen like SARS-CoV-2 relies on the activation of naive T cells. To investigate whether the primary CD8 + T-cell response against this virus is defective in advanced age, we used an in vitro approach to prime SARS-CoV-2-specific naive CD8 + T cells from healthy, unexposed donors of different age groups. Compared to younger adults, older individuals display a poor SARS-CoV-2-specific T-cell priming capacity in terms of both magnitude and quality of the response. In addition, older subjects recognize a lower number of epitopes. Our results implicate that immune aging is associated with altered primary SARS-CoV-2-specific CD8 + T-cell responses., 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 © 2021 Gallerani, Proietto, Dallan, Campagnaro, Pacifico, Albanese, Marzola, Marconi, Caputo, Appay, Gavioli and Nicoli.)

Background: The COVID-19 outbreak has heightened ongoing political debate about the international joint procurement of medicines and medical countermeasures. The European Union (EU) has developed what remains largely contractual and decentralized international procurement cooperation. The corona crisis has broadened and deepened public debate on such cooperation, in particular on the scope of cooperation, solidarity in the allocation of such cooperation, and delegation of cooperative decision-making. Crucial to political debate about these issues are public attitudes that constrain and undergird international cooperation., Methods: Our survey includes a randomized survey experiment (conjoint analysis) on a representative sample in five European countries in March 2020, informed by legal and policy debate on medical cooperation. Respondents choose and rate policy packages containing randomized mixes of policy attributes with respect to the scope of medicines covered, the solidarity in conferring priority access and the level of delegation., Results: In all country populations surveyed, the experiment reveals considerable popular support for European cooperation. Significant majorities preferred cooperation packages with greater rather than less scope of medicines regulated; with priority given to most in-need countries; and with delegation to EU-level rather than national expertise., Conclusion: Joint procurement raises delicate questions with regard to its scope, the inclusion of cross-border solidarity and the delegation of decision-making, that explain reluctance toward joint procurement among political decision-makers. This research shows that there is considerable public support across different countries in favor of centralization, i.e. a large scope and solidarity in the allocation and delegation of decision-making., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Public Health Association.)

Do crises bring us closer together? Many have observed how, during the Covid-19 pandemic, several European societies experienced a 'rally around the flag' effect. While this certainly took the form of support for incumbent governments, anecdotal evidence suggests that individuals' European identification may have been affected as well. In this paper, we exploit the unique timing and panel nature of a survey, whose respondents were interviewed in March/beginning of April 2020, again in July 2020, and finally in November 2022 to analyze whether a change in attachment to Europe occurred between the first and the second wave of the pandemic and with the Russian invasion of Ukraine. Our results show that the emotive dimension of EU attachment changed over the course of these crises, increasing both during the Covid pandemic and after the invasion of Ukraine. Our results support the view that symmetric crises tend to bring people closer together, suggesting that far-reaching EU-level actions in case of crises create, rather than require, a perception of belonging to an EU-level community. [ABSTRACT FROM AUTHOR]

Age-related changes in the immune system are thought to underlie the vulnerability of elderly individuals to emerging viral diseases, such as coronavirus disease 2019 (COVID-19). In this study, we used a fully validated in vitro approach to determine how age impacts the generation of de novo CD8+ T cell responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. Our data revealed a generalized deficit in the ability of elderly individuals to prime the differentiation of naïve precursors into effector CD8+ T cells defined by the expression of interferon (IFN)-γ and the transcription factor T-bet. As a consequence, there was an age-related decline in the diversity of newly generated CD8+ T cell responses targeting a range of typically immunodominant epitopes derived from SARS-CoV-2, accompanied by an overall reduction in the expression frequency of IFN-γ. These findings have potential implications for the development of new strategies to protect the elderly against COVID-19. [ABSTRACT FROM AUTHOR]

Advanced age is associated with severe symptoms and death upon SARS-CoV-2 infection. Virus-specific CD8+ T-cell responses have shown to be protective toward critical COVID-19 manifestations, suggesting that suboptimal cellular immunity may contribute to the age-pattern of the disease. The induction of a CD8+ T-cell response against an emerging pathogen like SARS-CoV-2 relies on the activation of naive T cells. To investigate whether the primary CD8+ T-cell response against this virus is defective in advanced age, we used an in vitro approach to prime SARS-CoV-2-specific naive CD8+ T cells from healthy, unexposed donors of different age groups. Compared to younger adults, older individuals display a poor SARS-CoV-2-specific T-cell priming capacity in terms of both magnitude and quality of the response. In addition, older subjects recognize a lower number of epitopes. Our results implicate that immune aging is associated with altered primary SARS-CoV-2-specific CD8+ T-cell responses. [ABSTRACT FROM AUTHOR]