Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity

Markov, Peter V; Katzourakis, Aris; Stilianakis, Nikolaos I.

doi:10.1038/s41579-022-00722-z

Cited by 210 publications

(273 citation statements)

References 11 publications

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“…Accordingly, as the human population acquires increasing levels of immunity through vaccination and/or infection; the evolutionary trajectory of SARS-CoV-2 toward increasing infectivity (through optimized host receptor binding), alone, will not satisfy its natural evolutionary drive toward increasing transmission rates. To combat the increasing immunity in the human population, SARS-CoV-2 is predicted to also evolve by escaping natural or vaccine induced immunity and gain the ability to infect previously protected individuals 43 . Thus, as SARS-CoV-2’s future evolution drives ever increasing levels of antigenic drift it is important that we characterize the correlates of protection and potential immune escape for both B cell and T cell human immunity, to guide future vaccine and diagnostic design.…”

Section: Discussionmentioning

confidence: 99%

The T cell epitope landscape of SARS-CoV-2 variants of concern

Tennøe

Gheorghe

Stratford

et al. 2022

Preprint

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During the COVID-19 pandemic, several SARS-CoV-2 variants of concern (VOC) emerged, bringing with them varying degrees of health and socioeconomic burdens. In particular, the Omicron VOC displayed distinct features of increased transmissibility accompanied by antigenic drift in the spike protein that partially circumvented the ability of pre-existing antibody responses in the global population to neutralize the virus. However, T cell immunity has remained robust throughout all the different VOC transmission waves and has emerged as a critically important correlate of protection against SARS-CoV-2 VOCs, in both vaccinated and infected individuals. Therefore, as SARS-CoV-2 VOCs continue to evolve, it is crucial that we characterize the correlates of protection and the potential for immune es-cape for both B cell and T cell human immunity in the population. Generating the insights necessary to understand T cell immunity, experimentally, for the global human population is at present critical but a time consuming, expensive, and laborious process. Further, it is not feasible to generate global or universal insights into T cell immunity in an actionable time frame for potential future emerging VOCs. However, using computational means we can expedite and provide early insights into the correlates of T cell protection. In this study, we generated and reveal insights on the T cell epitope landscape for the five main SARS-CoV-2 VOCs observed to date. We demonstrated here using a unique AI prediction platform, a strong concordance in global T cell protection across all mutated peptides for each VOC. This was modeled using the most frequent HLA alleles in the human population and covers the most common HLA haplotypes in the human population. The AI resource generated through this computational study and associated insights may guide the development of T cell vaccines and diagnostics that are even more robust against current and future VOCs, and their emerging subvariants.

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Section: Discussionmentioning

confidence: 99%

The T cell epitope landscape of SARS-CoV-2 variants of concern

Tennøe

Gheorghe

Stratford

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…SARS-CoV-2 changes rapidly through point mutations and recombination, and especially in its Spike and nucleocapsid regions [ 602 , 603 ]. This rapid ongoing evolution can alter the transmissibility and pathogenicity of the virus, and it may produce new variants that escape the host immune responses and that lead to more severe and fatal disease outcomes [ 604 , 605 , 606 ]. SARS-CoV-2 could also evolve to become less pathogenic [ 607 ].…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity and Risk of Bias in Studies Examining Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-Analysis

et al. 2022

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This systematic review and meta-analysis synthesized the evidence on the impacts of demographics and comorbidities on the clinical outcomes of COVID-19, as well as the sources of the heterogeneity and publication bias of the relevant studies. Two authors independently searched the literature from PubMed, Embase, Cochrane library, and CINAHL on 18 May 2021; removed duplicates; screened the titles, abstracts, and full texts by using criteria; and extracted data from the eligible articles. The variations among the studies were examined by using Cochrane, Q.; I2, and meta-regression. Out of 11,975 articles that were obtained from the databases and screened, 559 studies were abstracted, and then, where appropriate, were analyzed by meta-analysis (n = 542). COVID-19-related severe illness, admission to the ICU, and death were significantly correlated with comorbidities, male sex, and an age older than 60 or 65 years, although high heterogeneity was present in the pooled estimates. The study design, the study country, the sample size, and the year of publication contributed to this. There was publication bias among the studies that compared the odds of COVID-19-related deaths, severe illness, and admission to the ICU on the basis of the comorbidity status. While an older age and chronic diseases were shown to increase the risk of developing severe illness, admission to the ICU, and death among the COVID-19 patients in our analysis, a marked heterogeneity was present when linking the specific risks with the outcomes.

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“…While genome sequencing is ideal for characterisation of individual samples, large-scale testing based on genome sequencing has not to date been scaled for everyday practice. All diagnostic tests for SARS-CoV-2 face the challenge of a constantly mutating viral population with periodic emergence of viral variants that display fitness advantages that promote their transmission 32 . For nucleic acid based tests, such challenges to detect new variants arise for homology-based molecular tests (e.g.…”

Section: Discussionmentioning

confidence: 99%

Clinical Performance of Direct RT-PCR Testing of Raw Saliva for Detection of SARS-CoV-2 in Symptomatic and Asymptomatic Individuals

Castillo-Bravo

Lucca

Lai

et al. 2022

Preprint

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RT-qPCR tests based on RNA extraction from nasopharyngeal swab samples are promoted as the “gold standard” for SARS-CoV-2 detection. However, self-collected saliva samples offer a non-invasive alternative more suited to high-throughput testing. This study evaluated the performance of TaqPath COVID-19 Fast PCR Combo Kit 2.0 assay for detection of SARS-CoV-2 in raw saliva relative to a lab-developed direct RT-qPCR test (SalivaDirect-based PCR) and a RT-qPCR test based on RNA extraction from NPS samples. Both samples were collected from symptomatic and asymptomatic individuals (N=615). Saliva samples were tested for SARS-CoV-2 using the TaqPath COVID-19 Fast PCR Combo Kit 2.0 and the SalivaDirect-based PCR, while RNA extracts from NPS samples were tested by RT-qPCR according to the Irish national testing system. The TaqPath™ COVID-19 Fast PCR detected SARS-CoV-2 in 52 saliva samples, of which 51 were also positive with the SalivaDirect-based PCR. 49 samples displayed concordant results with the NPS extraction-based method, while three samples were positive on raw saliva. Among the negative samples, 10 discordant cases were found with the TaqPath COVID-19 Fast PCR (PPA–85.7%; NPA–99.5%), when compared to the RNA extraction-based NPS method, performing similarly to the SalivaDirect-based PCR (PPA-87.5%; NPA-99.5%). The direct RT-qPCR testing of saliva samples shows high concordance with NPS extraction-based method for SARS-CoV-2 detection, providing a cost-effective and highly-scalable system for high-throughput COVID-19 rapid-testing.

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Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity

Cited by 210 publications

References 11 publications

The T cell epitope landscape of SARS-CoV-2 variants of concern

The T cell epitope landscape of SARS-CoV-2 variants of concern

Heterogeneity and Risk of Bias in Studies Examining Risk Factors for Severe Illness and Death in COVID-19: A Systematic Review and Meta-Analysis

Clinical Performance of Direct RT-PCR Testing of Raw Saliva for Detection of SARS-CoV-2 in Symptomatic and Asymptomatic Individuals

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