Dataset Information

SARS-CoV-2 Evolution among Oncological Population: In-Depth Virological Analysis of a Clinical Cohort.

ABSTRACT: Oncological patients have a higher risk of prolonged SARS-CoV-2 shedding, which, in turn, can lead to evolutionary mutations and emergence of novel viral variants. The aim of this study was to analyze biological samples of a cohort of oncological patients by deep sequencing to detect any significant viral mutations. High-throughput sequencing was performed on selected samples from a SARS-CoV-2-positive oncological patient cohort. Analysis of variants and minority variants was performed using a validated bioinformatics pipeline. Among 54 oncological patients, we analyzed 12 samples of 6 patients, either serial nasopharyngeal swab samples or samples from the upper and lower respiratory tracts, by high-throughput sequencing. We identified amino acid changes D614G and P4715L as well as mutations at nucleotide positions 241 and 3037 in all samples. There were no other significant mutations, but we observed intra-host evolution in some minority variants, mainly in the ORF1ab gene. There was no significant mutation identified in the spike region and no minority variants common to several hosts. There was no major and rapid evolution of viral strains in this oncological patient cohort, but there was minority variant evolution, reflecting a dynamic pattern of quasi-species replication.

SUBMITTER: Laubscher F

PROVIDER: S-EPMC8540785 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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SARS-CoV-2 Evolution among Oncological Population: In-Depth Virological Analysis of a Clinical Cohort.

Laubscher Florian F Cordey Samuel S Friedlaender Alex A Schweblin Cecilia C Noetzlin Sarah S Simand Pierre-François PF Bordry Natacha N De Sousa Filipe F Pigny Fiona F Baggio Stephanie S Getaz Laurent L Dietrich Pierre-Yves PY Kaiser Laurent L Vu Diem-Lan DL

Microorganisms 20211014 10

<h4>Background</h4>Oncological patients have a higher risk of prolonged SARS-CoV-2 shedding, which, in turn, can lead to evolutionary mutations and emergence of novel viral variants. The aim of this study was to analyze biological samples of a cohort of oncological patients by deep sequencing to detect any significant viral mutations.<h4>Methods</h4>High-throughput sequencing was performed on selected samples from a SARS-CoV-2-positive oncological patient cohort. Analysis of variants and minorit ...[more]

PMID: 34683466

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Project description:Monoclonal antibodies (MAbs) targeting the Spike glycoprotein of SARS-CoV-2 is a key strategy to prevent severe COVID-19. Here, the efficacy of two monoclonal antibody bitherapies against SARS-CoV-2 was assessed on 92 patients at high risk of severe COVID-19 between March and October 2021 (Bichat-Claude Bernard Hospital, Paris, France). Nine patients died despite appropriate management. From 14 days following treatment initiation, we observed a slower viral load decay for patients treated with the bitherapy Bamlanivimab/Etsevimab compared to the Casirivimab/Imdevimab association therapy (P = 0.045). The emergence of several mutations on the Spike protein known to diminish antiviral efficacy was observed from 1 to 3 weeks after infusion. The Q493R mutation was frequently selected, located in a region of joint structural overlap by Bamlanivimab/Etsevimab antibodies. Despite that this study was done on former SARS-CoV-2 variants (Alpha and Delta), the results provide new insights into resistance mechanisms in SARS-CoV-2 antibodies neutralization escape and should be considered for current and novel variants. IMPORTANCE Monoclonal antibody bitherapies (MAbs) are commonly prescribed to treat severe SARS-CoV-2-positive patients, and the rapid growth of resistance mutation emergence is alarming globally. To explore this issue, we conducted both clinical and genomic analyses of SARS-CoV-2 in a series of patients treated in 2021. We first noticed that the two dual therapies prescribed during the study had different kinetics of viral load decay. Rapidly after initiation of the treatments, resistance mutations emerged in the interface between the MAbs and the target Spike glycoprotein, demonstrating the importance to continuously screen the viral genome during treatment course. Taken together, the results highlight that viral mutations may emerge under selective pressure, conferring a putative competitive advantage, and could rapidly spread, as observed for the Omicron variant.

Project description:BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has particularly impacted patients with hemato-oncological malignancies, as they showed not only a higher propensity for severe courses but also weaker immune responses after vaccination. Still, data on the influence of pandemic waves and vaccinations on outcomes are rare. This study aimed to analyze the timely course of infections and vaccinations in a real-life cohort of patients with hemato-oncological diseases.MethodsIn this cohort study, 1817 patients with hemato-oncological diseases from 1 February 2020 to 15 December 2022 at the 'Franz Tappeiner' Hospital in Merano/Meran, Italy, were followed for SARS-CoV-2 infections and vaccinations.ResultsOf 1817 patients with hemato-oncological malignancies, 735 (40.5%) were infected at least once with SARS-CoV-2, and 1614 (88.8%) received one or more doses of the approved vaccinations. Patients receiving antineoplastic treatment had a lower SARS-CoV-2 infection rate [35.1% versus 41.0%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95], but higher risk of hospitalization (13.4% versus 6.9%; OR 2.11, 95% CI 1.25-3.69) compared with untreated patients. Overall, the case fatality rate (CFR) was 3.4%. Unvaccinated patients were more prone to severe coronavirus disease 2019 (COVID-19) courses requiring hospitalization (OR 2.34, 95% CI 1.25-4.36) and had a higher CFR (7.3% versus 1.6%; OR 4.98, 95% CI 2.16-12.98) than their vaccinated counterparts. In the Delta wave, patients with two vaccinations had a lower infection risk (OR 0.18, 95% CI 0.10-0.35) and tendentially lower hospitalization rates (OR 0.25, 95% CI 0.05-1.29) than unvaccinated patients. In the Omicron wave, 345/1198 (28.8%) patients with three or more vaccinations had breakthrough infections, resulting in a similar risk for infection (OR 0.88, 95% CI 0.60-1.30) but numerically lower risk for hospitalization (24/345, 7.0%) than unvaccinated individuals (4/40, 10.0%). Scheduled visits were postponed in 128/335 (38.2%) patients due to COVID-19, and deferrals correlated with pandemic wave (P = 0.002) and vaccination status (P < 0.001).ConclusionsSARS-CoV-2 infections and outcomes differ between distinct phases of the pandemic. Vaccination with variant-specific vaccines should be prioritized as general protective measures are increasingly lifted.

Dataset Information

SARS-CoV-2 Evolution among Oncological Population: In-Depth Virological Analysis of a Clinical Cohort.

Publications

SARS-CoV-2 Evolution among Oncological Population: In-Depth Virological Analysis of a Clinical Cohort.

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