Distinct CD8+ T-cell types Associated with COVID-19 Severity in Unvaccinated HLA-A2+ Patients

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract Although emerging data have revealed the critical role of memory CD8 + T cells in preventing and controlling SARS-CoV-2 infection, virus-specific T-cell responses against its innate-like subsets unvaccinated COVID-19 patients with various disease manifestations an HLA-restricted fashion remain to be understood. Here, we show strong association protective cellular immunity mild unique cell types virus HLA-A2 restricted manner. ELISpot assays reveal that SARS-CoV-2-specific are significantly higher than severe patients, whereas neutralizing antibody correlate severity. Single-cell analyses HLA-A2-restricted cells, which recognize highly conserved immunodominant epitopes, demonstrate divergent profiles versus disease. including cytotoxic KLRB1 CD8αα signatures, IFNG hi ID3 IL7R proliferative stem cell-like preferentially observed COVID-19, distinct terminally-differentiated predominantly detected COVID-19: activated FASL early-terminated or dysfunctional IL4R GATA3 subset. In conclusion, our findings suggest contrasting may dictate Figure Graphical abstract. epitope-specific subtypes associated patients. Potent gene signature (upper) (lower).

Language: Английский

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Human respiratory syncytial virus genetic diversity and lineage replacement in Ireland pre- and post-COVID-19 pandemic

Microbial Genomics, Journal Year: 2025, Volume and Issue: 11(3)

Published: March 17, 2025

Human respiratory syncytial virus (HRSV) is a common cause of lower tract infections globally, and changes in viral epidemiology have been observed many jurisdictions following the coronavirus disease 2019 (COVID-19) pandemic. Newly licensed vaccines monoclonal antibodies are anticipated to alleviate burden on healthcare systems, though such interventions may exert selective pressures evolution. To evaluate diversity HRSV Ireland pre- post-COVID-19 pandemic, whole-genome sequencing was performed HRSV-A ( n =123) -B =110) samples collected from community hospitalized cases, during three seasons between 2021 2024. Additionally, G gene sequences, =141) =141), 2015–2019 period were examined. Lineages assigned by phylogenetic analyses including reference lineages. Phylogenetic trees inferred with whole genomes consistent. Changes prevalence certain lineages reflected impact non-pharmaceutical (NPIs) introduced reduce severe acute syndrome 2 transmission, A.D.1 A.D.5 dominant B.D.E.1 most prevalent HRSV-B lineage. Similar trends circulating across Europe this time. The emergence new lineage identified as descendant A.D.1, eight distinctive substitutions proteins G, F L. Other aa glycoprotein, which could nirsevimab binding. We provide first comprehensive analysis genomic evolution over last decade NPIs COVID-19 This study provides foundation for future public health surveillance employing pathogen genomics enable an evidence-based assessment pharmaceutical severity.

Language: Английский

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Impact of Vaccination on Intra-Host Genetic Diversity of Patients Infected with SARS-CoV-2 Gamma Lineage

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1524 - 1524

Published: Sept. 26, 2024

The high transmissibility, rapid evolution, and immune escape of SARS-CoV-2 variants can influence the course infection and, in turn, morbidity mortality COVID-19, posing a challenge controlling transmission rates contributing to emergence spread new variants. Understanding factors that shape viral genetic variation is essential for comprehending evolution SARS-CoV-2, especially vaccinated individuals where response plays role progression this disease. In context, we evaluated impact immunity induced by CoronaVac vaccine (Butantan/Sinovac) on intra-host diversity, analyzing 118 whole-genome sequences from unvaccinated patients infected with Gamma variant. Vaccination favors negative selection at level different genomic regions. It prevents greater diversity reinforcing importance vaccination reducing mutations virus transmission.

Language: Английский

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Intra-host variability of SARS-CoV-2: Patterns, causes and impact on COVID-19

Virology, Journal Year: 2024, Volume and Issue: 603, P. 110366 - 110366

Published: Dec. 22, 2024

Language: Английский

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