SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19

Stanevich, Oksana V.; Alekseeva, Evgeniia; Sergeeva, Maria V.; Fadeev, Artem; Komissarova, Kseniya; Ivanova, Anna; Simakova, Tamara; Vasilyev, Kirill; Shurygina, Anna-Polina; Stukova, Marina; Safina, Ksenia R; Nabieva, Elena; Garushyants, Sofya K.; Klink, Galya V.; Bakin, Evgeny; Zabutova, Jullia; Kholodnaya, A. N.; Lukina, O. V.; Skorokhod, Irina; Ryabchikova, Viktoria; Медведева, Н. А.; Lioznov, Dmitry; Danilenko, Daria; Chudakov, Dmitriy M.; Komissarov, Andrey; Bazykin, Georgii A.

doi:10.21203/rs.3.rs-750741/v1

Cited by 12 publications

(14 citation statements)

References 26 publications

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“…gaining or losing a mutation compared to the individual’s first sample) per week (Table S3), compared to the approximately 0.5 mutations expected in between-host transmission. Further, in these studies, deletions (notably, the 69/70 deletion found in Alpha and the BA.1 sub-lineage of Omicron) have been found to both increase and decrease in frequency along the time period of infection (Kemp et al 2021; Stanevich et al 2021). As it is unlikely that a deletion could be reverted, this is evidence for multiple coexisting viral populations (Lythgoe et al 2021).…”

Section: Discussionmentioning

confidence: 86%

“…There are a number of studies on chronically or persistently infected individuals which contain longitudinal sampling of the viruses present (Avanzato et al 2020;Choi et al 2020;Clark et al 2021;Karim et al 2021;Kemp et al 2021;Ramírez et al 2021;Stanevich et al 2021;Voloch et al 2020;Weigang et al 2021;Williamson et al 2021). Across these studies, there were an average of 4.0 (95% confidence interval: 0.63 to 9.76) evolutionary events (i.e.…”

Section: Figure 2 | A) Two Different Scenarios Of How the Shared Muta...mentioning

confidence: 99%

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The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

Hill

Plessis

Peacock

et al. 2022

Preprint

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The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic branch with an increased evolutionary rate, along which only two sequences have been sampled. Alpha genomes comprise a well-supported monophyletic clade within which the evolutionary rate is more typical of SARS-CoV-2. The Alpha epidemic continued to grow despite the continued restrictions on social mixing across the UK, and the imposition of new restrictions, in particular the English national lockdown in November 2020. While these interventions succeeded in reducing the absolute number of cases, the impact of these non-pharmaceutical interventions was predominantly to drive the decline of the SARS-CoV-2 lineages which preceded Alpha. We investigate the only two sampled sequences that fall on the branch ancestral to Alpha. We find that one is likely to be a true intermediate sequence, providing information about the order of mutational events that led to Alpha. We explore alternate hypotheses that can explain how Alpha acquired a large number of mutations yet remained largely unobserved in a region of high genomic surveillance: an under-sampled geographical location, a non-human animal population, or a chronically-infected individual. We conclude that the last hypothesis provides the best explanation of the observed behaviour and dynamics of the variant, although we find that the individual need not be immunocompromised, as persistently-infected immunocompetent hosts also display a higher within-host rate of evolution. Finally, we compare the ancestral branches and mutation profiles of other VOCs to each other, and identify that Delta appears to be an outlier both in terms of the genomic locations of its defining mutations, and its lack of rapid evolutionary rate on the ancestral branch. As new variants, such as Omicron, continue to evolve (potentially through similar mechanisms) it remains important to investigate the origins of other variants to identify ways to potentially disrupt their evolution and emergence.

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Section: Discussionmentioning

confidence: 86%

Section: Figure 2 | A) Two Different Scenarios Of How the Shared Muta...mentioning

confidence: 99%

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

Hill

Plessis

Peacock

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Stanevich et al identified NSP3:T504P as a mutation associated with cytotoxic T cell epitope immune escape (Stanevich et al, 2021).…”

Section: Orf1ab-nsp3 Recurrent Mutationsmentioning

confidence: 99%

Recurrent SARS-CoV-2 Mutations in Immunodeficient Patients

Wilkinson

Richter

Casey

et al. 2022

Preprint

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Long-term SARS-CoV-2 infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COG-UK dataset. The spike gene receptor binding domain (RBD) and N-terminal domains (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, - T30I was determined to be the most recurrent frequently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation. There is an apparent selective pressure for mutations which aid intra-host transmission or persistence which are often different to mutations which aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted.

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“…At the same time, it has been shown that long-term COVID19 in immunocompromised hosts may result in the appearance of new variants of SARS-Cov2 virus with changed properties, which contribute to virus' ability to escape from cellular immunity. Stanevich et al report a case of intrahost SARS-Cov2 evolution in which the virus acquired 40 changes [89]. Among the accumulated mutations, 12 reduced or prevented binding of known immunogenic SARS-CoV-2 HLA class I antigens, suggesting that virus immunoediting is largely driven by cytotoxic CD8+ T cell clones.…”

Section: Vaccine-induced Immunity To Sars-cov-2mentioning

confidence: 99%

Peculiarities of the T Cell Immune Response in COVID-19

2022

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Understanding the T cell response to SARS-CoV-2 is critical to vaccine development, epidemiological surveillance, and control strategies for this disease. This review provides data from studies of the immune response in coronavirus infections. It describes general mechanisms of immunity, its T cell components, and presents a detailed scheme of the T cell response in SARS-CoV-2 infection, including from the standpoint of determining the most promising targets for assessing its level. In addition, we reviewed studies investigating post-vaccination immunity in the development of vaccines against COVID-19. This review also includes the peculiarities of immunity in different age and gender groups, and in the presence of a number of factors, for example, comorbidity or disease severity. This study summarizes the most informative methods for assessing the immune response to SARS-CoV-2 infection.

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SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19

Cited by 12 publications

References 26 publications

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK

Recurrent SARS-CoV-2 Mutations in Immunodeficient Patients

Peculiarities of the T Cell Immune Response in COVID-19

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