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

• Published in: BMC infectious diseases Vol. 24; no. 1; pp. 1139 - 18
• Main Authors: Holtz, Andrew, Van Weyenbergh, Johan, Hong, Samuel L, Cuypers, Lize, O'Toole, Áine, 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, Jérémie, Verhasselt, Bruno, Laffut, Wim, Vael, Carl, Goegebuer, Truus, van der Kant, Rob, Rousseau, Frederic, Schymkowitz, Joost, Serrano, Luis, Delgado, Javier, Wenseleers, Tom, Bours, Vincent, André, Emmanuel, Suchard, Marc A, Rambaut, Andrew, Dellicour, Simon, Maes, Piet, Durkin, Keith, Baele, Guy
• Format: Journal Article Web Resource
• Language: English
• Published: England BioMed Central Ltd 10-10-2024; BioMed Central; Springer Science and Business Media LLC; BMC
• Subjects: Adult; Aged; Amino acids; Belgium; Belgium - epidemiology; Cell activation; Complement activation; Complement system; COVID-19; COVID-19 - epidemiology; COVID-19 - immunology; COVID-19 - virology; Disease spread; Epidemiology; Fatalities; Female; Genomes; Genomic epidemiology; Health aspects; Helper cells; Human health sciences; Humans; Immune response; Immune system; Immunologie & maladie infectieuse; Immunology & infectious disease; Infectious Diseases; Insertion; Lymphocytes T; Male; Metadata; Middle Aged; Mutation; Nasopharynx; Nasopharynx - virology; Nursing homes; Outbreaks; Phylodynamics; Phylogeography; Proteins; SARS-CoV-2; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 variants; Sciences de la santé humaine; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike protein; spike protein, SARS-CoV-2; Travel; Travel patterns; Travelers; Viral diseases; Belgium; Congo (Kinshasa); France; Congo-Democratic Republic of Congo; Central Africa; Switzerland; Europe; COVID-19; SARS-CoV-2; Genomic epidemiology; Disease spread; Phylodynamics; Phylogeography
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-024-09967-w

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.