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00925njm 22002777a 4500 dc López, Mariana G author Chiner-Oms, Álvaro author García de Viedma, Darío author Ruiz-Rodriguez, Paula author Bracho, Maria Alma author Cancino-Muñoz, Irving author D'Auria, Giuseppe author de Marco, Griselda author García-González, Neris author Goig, Galo Adrian author Gómez-Navarro, Inmaculada author Jiménez-Serrano, Santiago author Martinez-Priego, Llúcia author Ruiz-Hueso, Paula author Ruiz-Roldán, Lidia author Torres-Puente, Manuela author Alberola, Juan author Albert, Eliseo author Aranzamendi Zaldumbide, Maitane author Bea-Escudero, María Pilar author Boga, Jose Antonio author Bordoy, Antoni E author Canut-Blasco, Andrés author Carvajal, Ana author Cilla Eguiluz, Gustavo author Cordón Rodríguez, Maria Luz author Costa-Alcalde, José J author de Toro, María author de Toro Peinado, Inmaculada author Del Pozo, Jose Luis author Duchêne, Sebastián author Fernández-Pinero, Jovita author Fuster Escrivá, Begoña author Gimeno Cardona, Concepción author González Galán, Verónica author Gonzalo Jiménez, Nieves author Hernáez Crespo, Silvia author Herranz, Marta author Lepe, José Antonio author López-Causapé, Carla author López-Hontangas, José Luis author Martín, Vicente author Martró, Elisa author Milagro Beamonte, Ana author Montes Ros, Milagrosa author Moreno-Muñoz, Rosario author Navarro, David author Navarro-Marí, José María author Not, Anna author Oliver, Antonio author Palop-Borrás, Begoña author Parra Grande, Mónica author Pedrosa-Corral, Irene author Pérez González, Maria Carmen author Pérez-Lago, Laura author Pérez-Ruiz, Mercedes author Piñeiro Vázquez, Luis author Rabella, Nuria author Rezusta, Antonio author Robles Fonseca, Lorena author Rodríguez-Villodres, Ángel author Sanbonmatsu-Gámez, Sara author Sicilia, Jon author Soriano, Alex author Tirado Balaguer, María Dolores author Torres, Ignacio author Tristancho, Alexander author Marimón, José María author Coscolla, Mireia author González-Candelas, Fernando author Comas, Iñaki author 2021 The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants. Nat Genet . 2021 Oct;53(10):1405-1414. doi: 10.1038/s41588-021-00936-6. Epub 2021 Sep 30. 10.1038/s41588-021-00936-6 1546-1718 Nature genetics 34594042 http://hdl.handle.net/20.500.12105/15129 The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant.