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We are grateful to the diagnostics and sequencing laboratories in all countries included in this study, particularly the Republic of the Congo, France, Switzerland, and Belgium for their efforts in screening, sequencing, and publicizing their genomic data. GD is supported by the European Molecular Biology Organization (EMBO) Installation Grant (IG) EMBO-IG-5305-2023. AH acknowledges Ecole doctorale Frontieres de l'Innovation en Recherche et Education-Programme Bettencourt. AH is funded by the INCEPTION programme (Investissements d'Avenir grant ANR-16-CONV-0005). MAS is supported in part through US National Institutes of Health grants U01 AI135995, R01 AI153044 and R01 AI162611.SD acknowledges support from the Fonds National de la Recherche Scientifique (F.R.S.-FNRS, Belgium; grant n degrees F.4515.22) and from the European Union Horizon 2020 project MOOD (grant agreement n degrees 874850). SD and GB acknowledge support from the Research Foundation-Flanders (Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, FWO, Belgium; grant n degrees G098321N). JVW acknowledges support from the Research Foundation-Flanders (Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, FWO, Belgium; grant n degrees G0A0621N and G065421N). GB acknowledges support from the Research Foundation-Flanders (Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, FWO, Belgium; grant n degrees G0E1420N), from the Internal Funds KU Leuven (Grant No. C14/18/094), and from the DURABLE EU4Health project 02/2023-01/2027, which is co-funded by the European Union (call EU4H-2021-PJ4) under Grant Agreement No. 101102733. UZ Leuven, as national reference centre for respiratory pathogens, is supported by Sciensano, which is gratefully acknowledged.

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Emergence of the B.1.214.2 SARS-CoV-2 lineage with an Omicron-like spike insertion and a unique upper airway immune signature

Publicated to:Bmc Infectious Diseases. 24 (1): 1139- - 2024-10-10 24(1), DOI: 10.1186/s12879-024-09967-w

Authors: Holtz, Andrew; Van Weyenbergh, Johan; Hong, Samuel L; Cuypers, Lize; O'Toole, Aine; Dudas, Gytis; Gerdol, Marco; Potter, Barney I; Ntoumi, Francine; Mapanguy, Claujens Chastel Mfoutou; Vanmechelen, Bert; Wawina-Bokalanga, Tony; Van Holm, Bram; Menezes, Soraya Maria; Soubotko, Katja; Van Pottelbergh, Gijs; Wollants, Elke; Vermeersch, Pieter; Jacob, Ann-Sophie; Maes, Brigitte; Obbels, Dagmar; Matheeussen, Veerle; Martens, Geert; Gras, Jeremie; Verhasselt, Bruno; Laffut, Wim; Vael, Carl; Goegebuer, Truus; van der Kant, Rob; Rousseau, Frederic; Schymkowitz, Joost; Serrano, Luis; Delgado, Javier; Wenseleers, Tom; Bours, Vincent; Andre, Emmanuel; Suchard, Marc A; Rambaut, Andrew; Dellicour, Simon; Maes, Piet; Durkin, Keith; Baele, Guy

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Abstract

We investigate the emergence, mutation profile, and dissemination of SARS-CoV-2 lineage B.1.214.2, first identified in Belgium in January 2021. This variant, featuring a 3-amino acid insertion in the spike protein similar to the Omicron variant, was speculated to enhance transmissibility or immune evasion. Initially detected in international travelers, it substantially transmitted in Central Africa, Belgium, Switzerland, and France, peaking in April 2021. Our travel-aware phylogeographic analysis, incorporating travel history, estimated the origin to the Republic of the Congo, with primary European entry through France and Belgium, and multiple smaller introductions during the epidemic. We correlate its spread with human travel patterns and air passenger data. Further, upon reviewing national reports of SARS-CoV-2 outbreaks in Belgian nursing homes, we found this strain caused moderately severe outcomes (8.7% case fatality ratio). A distinct nasopharyngeal immune response was observed in elderly patients, characterized by 80% unique signatures, higher B- and T-cell activation, increased type I IFN signaling, and reduced NK, Th17, and complement system activation, compared to similar outbreaks. This unique immune response may explain the variant's epidemiological behavior and underscores the need for nasal vaccine strategies against emerging variants.

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