tetano
Editor, Senior Moderator
Matilda Berkell[SUP]1,2,*[/SUP] 
, Anna Górska[SUP]3,*[/SUP] , Mathias Smet[SUP]1,2,*[/SUP] , Delphine Bachelet[SUP]4,5,*[/SUP] , Elisa Gentilotti[SUP]3,**[/SUP] , Mariana Guedes[SUP]3,**[/SUP] , Anna Maria Franco-Yusti[SUP]4,6,**[/SUP] , Fulvia Mazzaferri[SUP]3[/SUP] , Erley Lizarazo Forero[SUP]7[/SUP] , Veerle Matheeussen[SUP]1[/SUP] , Benoit Visseaux[SUP]6[/SUP] , Zaira R. Palacios-Baena[SUP]8,9[/SUP] , Natascia Caroccia[SUP]10,11[/SUP] , Aline-Marie Florence[SUP]4,5[/SUP] , Charlotte Charpentier[SUP]4,6[/SUP] , Coretta van Leer[SUP]7[/SUP] , Maddalena Giannella[SUP]10,11[/SUP] , Alex W. Friedrich[SUP]7[/SUP] , Jesús Rodríguez-Baño[SUP]8,9[/SUP] , Jade Ghosn[SUP]4,12[/SUP] , ORCHESTRA working group[SUP]13[/SUP] , Samir Kumar-Singh[SUP]1,2[/SUP] , Cedric Laouénan[SUP]4,5[/SUP] , Evelina Tacconelli[SUP]3,***[/SUP] , Surbhi Malhotra-Kumar[SUP]1,**[/SUP]
Background
Evolution of SARS-CoV-2 is continuous.
Aim
Between 01/2020 and 02/2022, we studied SARS-CoV-2 variant epidemiology, evolution and association with COVID-19 severity.
Methods
In 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.
Results
Overall, 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
614G. 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).
Conclusion
Specific mutations correlate with COVID-19 severity. Quasi-species potentially shaping VOCs’ emergence are relevant to consider.
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2025.30.10.2400038
, Anna Górska[SUP]3,*[/SUP] , Mathias Smet[SUP]1,2,*[/SUP] , Delphine Bachelet[SUP]4,5,*[/SUP] , Elisa Gentilotti[SUP]3,**[/SUP] , Mariana Guedes[SUP]3,**[/SUP] , Anna Maria Franco-Yusti[SUP]4,6,**[/SUP] , Fulvia Mazzaferri[SUP]3[/SUP] , Erley Lizarazo Forero[SUP]7[/SUP] , Veerle Matheeussen[SUP]1[/SUP] , Benoit Visseaux[SUP]6[/SUP] , Zaira R. Palacios-Baena[SUP]8,9[/SUP] , Natascia Caroccia[SUP]10,11[/SUP] , Aline-Marie Florence[SUP]4,5[/SUP] , Charlotte Charpentier[SUP]4,6[/SUP] , Coretta van Leer[SUP]7[/SUP] , Maddalena Giannella[SUP]10,11[/SUP] , Alex W. Friedrich[SUP]7[/SUP] , Jesús Rodríguez-Baño[SUP]8,9[/SUP] , Jade Ghosn[SUP]4,12[/SUP] , ORCHESTRA working group[SUP]13[/SUP] , Samir Kumar-Singh[SUP]1,2[/SUP] , Cedric Laouénan[SUP]4,5[/SUP] , Evelina Tacconelli[SUP]3,***[/SUP] , Surbhi Malhotra-Kumar[SUP]1,**[/SUP]Background
Evolution of SARS-CoV-2 is continuous.
Aim
Between 01/2020 and 02/2022, we studied SARS-CoV-2 variant epidemiology, evolution and association with COVID-19 severity.
Methods
In 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.
Results
Overall, 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
614G. 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).Conclusion
Specific mutations correlate with COVID-19 severity. Quasi-species potentially shaping VOCs’ emergence are relevant to consider.
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2025.30.10.2400038