Chronic viral infections are ubiquitous in humans, with individuals carrying multiple viruses that can reactivate during physiological stress, including severe illness1. Notably, SARS-CoV-2 infection has been shown to reactivate chronic viruses such as Epstein–Barr virus and cytomegalovirus, yet the full extent, temporal dynamics and immunological impact of viral reactivation in COVID-19 remain incompletely understood2, 3, 4, 5, 6–7. Here, leveraging multi-omic longitudinal data from 1,154 hospitalized patients with COVID-19 from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, we reveal significant reactivation of Herpesviridae and Anelloviridae during acute COVID-19, with distinct temporal dynamics for different viruses, and demonstrate that reactivation correlates with disease severity, host immune effects and clinical outcomes. Although our results do not establish causation between virus reactivation and clinical outcomes, we highlight the prevalence of chronic viral reactivation during acute COVID-19 and long COVID. Our findings challenge the prevailing view that chronic viral reactivation is primarily a consequence of immunosuppression, demonstrating that reactivations occur frequently in immunocompetent individuals during severe illness and in association with increased systemic inflammation. Additionally, we demonstrate persistence of viral reactivation in convalescence, and report an association of Anelloviridae with long COVID. This study provides immune, transcriptomic and metabolomic signatures of viral reactivation that could inform future strategies to prognosticate and treat acute COVID-19 and long COVID. Chronic reactivation of distinct herpesviruses and anelloviruses occur during acute and long COVID-19, and track with disease severity, inflammation and outcomes, revealing immune signatures with prognostic potential.
Cole P. Maguire, Jing Chen, Nadine Rouphael et al.· Nature· 3 citations
The complement system is a major effector system of the humoral immune response, but its capacity to cooperate with antibodies to inhibit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a host remains poorly characterized. Here, we combined authentic virus neutralization, antibody engineering, and single viral particle analysis by flow virometry to show that complement enhances antibody neutralization of SARS-CoV-2. Addition of complement increased neutralization titers of sera from convalescent individuals (n = 14), vaccinated individuals (n = 15), and individuals with hybrid immunity (n = 15) against D614G, BA.1, XBB.1.5, and JN.1 variants by up to 42-fold. D614G and BA.1 displayed a high level of neutralization, which was only slightly improved by adding complement. Conversely, neutralization of XBB.1.5 and JN.1 was weak but strongly enhanced by complement. Among the 32 JN.1 nonneutralizers, 22 regained detectable neutralization in the presence of complement. The enhancement mainly relied on cross-reactive anti-S2 antibodies, but monoclonal antibodies targeting the receptor binding domain and N-terminal domain could also be augmented. Viral inhibition required antibody Fc hexamerization, C1q recruitment, and C3 deposition, but it was independent of the membrane attack complex formed by C9. Consistently, complement components were deposited at the surfaces of viral particles with no detectable virolysis. In sera from individuals with severe COVID-19, both complement-mediated neutralization and anti-S2 antibody levels were associated with improved survival. Overall, our data show that complement potentiates the ability of antispike antibodies to neutralize immune-evasive SARS-CoV-2 variants.
M. Jungbauer-Groznica, Pierre Rosenbaum, I. Staropoli et al.· Science Translational Medici...· 0 citations
OBJECTIVE
The study aims to identify and characterize the SARS-Cov-2 variants circulating in West and Central Africa during the pandemic, between 2020 and 2022.
METHODS
From early 2020 to late 2022, naso-pharyngeal or oro-pharyngeal samples were collected in five countries: Burkina Faso, Côte d'Ivoire, Mali, Republic of Congo and Chad. SARS-CoV-2 positive samples (Ct-value < 30) were sequenced to identify the circulating variants in these countries during the different waves of the pandemic.
RESULTS
Overall, 793 whole genomes of SARS-Cov-2 were generated: 308 in Côte d'Ivoire, 244 in the Republic of Congo, 91 in Chad, 87 in Burkina Faso and 63 in Mali. In 2020, early variants detected included B.1 and B.1.1. Lineage A.21 was identified in both Burkina Faso and Mali, while lineages A and A.18 were detected in Côte d'Ivoire and Mali. Some variants appeared to be country-specific, such as lineage B.1.1.404 in Burkina Faso. Chad exhibited a distinct pattern compared with the other countries, with Delta variants detected earlier than in the other locations. In 2021, the diversity of circulating variants increased and differed more markedly between countries. In 2022, the variant landscape was dominated by Omicron lineages in all countries.
CONCLUSION
This study provides new resources concerning the SARS-CoV-2 variants circulating in West and Central Africa between 2020 and 2022, which are less represented in global datasets. The variants identified in this study were similar to the variants observed in other regions of the world.
Guilbaud Romane, Almoustapha I. Maiga, Abdoul-Salam Ouédraogo et al.· Journal of Infection and Pub...· 0 citations
The development of an effective anti-HIV vaccine remains a critical tool to halt the HIV epidemic, particularly due to the limits of the PrEP strategies. CD4+ T lymphocytes play a crucial role in vaccine efficacy; however, they are also the primary target cells for HIV infection. Given these opposing roles, we hypothesized that an in-depth characterization of CD4+ T cell responses to vaccination will elucidate mechanisms of protection.
To test this hypothesis, we immunized rhesus macaques using a prime-boost strategy that included a DV1-DNA prime and boosts with ALVAC alone or in combination with DV1-gp120 protein, followed by intravaginal exposures to SIVmac251. We then integrated data obtained by flow cytometry and plasma proteome analyses, as well as transcriptome and chromatin accessibility analyses of CD3+ cells, to investigate how the vaccine shapes the CD4+ T cell immunity and how these responses cooperate in reducing the acquisition.
We found that DV1 DNA/ALVAC/gp120 vaccine elicited envelope-specific immunomodulatory Tr1 CD4+ T cells, and that total Tr1 responses were associated with a reduced risk of viral acquisition. Transcriptome analyses of CD3+ cells identified vaccine-induced Tr1, as well as IL-27, gene signatures that were associated with a reduced risk, confirming the protective role of these cells. Furthermore, the study of the epigenetic landscape of CD3+ cells revealed that the epigenetic reprogramming of enhancer region upstream of the transcription factors BATF and IRF-1, which are involved in the development of Tr1 cells, correlated with lower viral acquisition.
These data suggest that immunoinhibitory Tr1 cells contribute to vaccine efficacy by decreasing inflammation and potentially counteracting the development and recruitment of HIV target cells.
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Vaccines and Immunotherapy (VAC)
Massimiliano Bissa, S. Fourati, Sohyoung Kim et al.· Journal of Immunology· 0 citations
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