Matilda Berkell, Anna Górska, Mathias Smet, Delphine Bachelet, Elisa Gentilotti, Mariana Guedes, Anna Maria Franco-Yusti, Fulvia Mazzaferri, Erley Lizarazo Forero, Veerle Matheeussen, Benoit Visseaux, Zaira R Palacios-Baena, Natascia Caroccia, Aline-Marie Florence, Charlotte Charpentier, Coretta van Leer, Maddalena Giannella, Alex W Friedrich, Jesús Rodríguez-Baño, Jade Ghosn, Samir Kumar-Singh, Cedric Laouénan, Evelina Tacconelli, Surbhi Malhotra-Kumar
{"title":"Quasi-species prevalence and clinical impact of evolving SARS-CoV-2 lineages in European COVID-19 cohorts, January 2020 to February 2022.","authors":"Matilda Berkell, Anna Górska, Mathias Smet, Delphine Bachelet, Elisa Gentilotti, Mariana Guedes, Anna Maria Franco-Yusti, Fulvia Mazzaferri, Erley Lizarazo Forero, Veerle Matheeussen, Benoit Visseaux, Zaira R Palacios-Baena, Natascia Caroccia, Aline-Marie Florence, Charlotte Charpentier, Coretta van Leer, Maddalena Giannella, Alex W Friedrich, Jesús Rodríguez-Baño, Jade Ghosn, Samir Kumar-Singh, Cedric Laouénan, Evelina Tacconelli, Surbhi Malhotra-Kumar","doi":"10.2807/1560-7917.ES.2025.30.10.2400038","DOIUrl":null,"url":null,"abstract":"<p><p>BackgroundEvolution of SARS-CoV-2 is continuous.AimBetween 01/2020 and 02/2022, we studied SARS-CoV-2 variant epidemiology, evolution and association with COVID-19 severity.MethodsIn nasopharyngeal swabs of COVID-19 patients (n = 1,762) from France, Italy, Spain, and the Netherlands, SARS-CoV-2 was investigated by reverse transcription-quantitative PCR and whole-genome sequencing, and the virus variant/lineage (NextStrain/Pangolin) was determined. Patients' demographic and clinical details were recorded. Associations between mild/moderate or severe COVID-19 and SARS-CoV-2 variants and patient characteristics were assessed by logistic regression. Rates and genomic locations of mutations, as well as quasi-species distribution (≥ 2 heterogeneous positions, ≥ 50× coverage) were estimated based on 1,332 high-quality sequences.ResultsOverall, 11 SARS-CoV-2 clades infected 1,762 study patients of median age 59 years (interquartile range (IQR): 45-73), with 52.5% (n = 925) being male. In total, 101 non-synonymous substitutions/insertions correlated with disease prognosis (severe, n = 27; mild-to-moderate, n = 74). Several hotspots (mutation rates ≥ 85%) occurred in Alpha, Delta, and Omicron variants of concern (VOCs) but none in pre-Alpha strains. Four hotspots were retained across all study variants, including spike:D614G. Average number of mutations per open-reading-frame (ORF) increased in the spike gene (average < 5 per genome in January 2020 to > 15 in 2022), but remained stable in ORF1ab, membrane, and nucleocapsid genes. Quasi-species were most prevalent in 20A/EU2 (48.9%), 20E/EU1 (48.6%), 20A (38.8%), and 21K/Omicron (36.1%) infections. Immunocompromised status and age (≥ 60 years), while associated with severe COVID-19 or death irrespective of variant (odds ratio (OR): 1.60-2.25; p ≤ 0.014), did not affect quasi-species' prevalence (p > 0.05).ConclusionSpecific mutations correlate with COVID-19 severity. Quasi-species potentially shaping VOCs' emergence are relevant to consider.</p>","PeriodicalId":12161,"journal":{"name":"Eurosurveillance","volume":"30 10","pages":""},"PeriodicalIF":9.9000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Eurosurveillance","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2807/1560-7917.ES.2025.30.10.2400038","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
BackgroundEvolution of SARS-CoV-2 is continuous.AimBetween 01/2020 and 02/2022, we studied SARS-CoV-2 variant epidemiology, evolution and association with COVID-19 severity.MethodsIn nasopharyngeal swabs of COVID-19 patients (n = 1,762) from France, Italy, Spain, and the Netherlands, SARS-CoV-2 was investigated by reverse transcription-quantitative PCR and whole-genome sequencing, and the virus variant/lineage (NextStrain/Pangolin) was determined. Patients' demographic and clinical details were recorded. Associations between mild/moderate or severe COVID-19 and SARS-CoV-2 variants and patient characteristics were assessed by logistic regression. Rates and genomic locations of mutations, as well as quasi-species distribution (≥ 2 heterogeneous positions, ≥ 50× coverage) were estimated based on 1,332 high-quality sequences.ResultsOverall, 11 SARS-CoV-2 clades infected 1,762 study patients of median age 59 years (interquartile range (IQR): 45-73), with 52.5% (n = 925) being male. In total, 101 non-synonymous substitutions/insertions correlated with disease prognosis (severe, n = 27; mild-to-moderate, n = 74). Several hotspots (mutation rates ≥ 85%) occurred in Alpha, Delta, and Omicron variants of concern (VOCs) but none in pre-Alpha strains. Four hotspots were retained across all study variants, including spike:D614G. Average number of mutations per open-reading-frame (ORF) increased in the spike gene (average < 5 per genome in January 2020 to > 15 in 2022), but remained stable in ORF1ab, membrane, and nucleocapsid genes. Quasi-species were most prevalent in 20A/EU2 (48.9%), 20E/EU1 (48.6%), 20A (38.8%), and 21K/Omicron (36.1%) infections. Immunocompromised status and age (≥ 60 years), while associated with severe COVID-19 or death irrespective of variant (odds ratio (OR): 1.60-2.25; p ≤ 0.014), did not affect quasi-species' prevalence (p > 0.05).ConclusionSpecific mutations correlate with COVID-19 severity. Quasi-species potentially shaping VOCs' emergence are relevant to consider.
期刊介绍:
Eurosurveillance is a European peer-reviewed journal focusing on the epidemiology, surveillance, prevention, and control of communicable diseases relevant to Europe.It is a weekly online journal, with 50 issues per year published on Thursdays. The journal includes short rapid communications, in-depth research articles, surveillance reports, reviews, and perspective papers. It excels in timely publication of authoritative papers on ongoing outbreaks or other public health events. Under special circumstances when current events need to be urgently communicated to readers for rapid public health action, e-alerts can be released outside of the regular publishing schedule. Additionally, topical compilations and special issues may be provided in PDF format.