A Founder Effect Led Early Sars-Cov-2 Transmission In Spain

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome analysis has identified five large clades worldwide which emerged in 2019(19A and 19B) and in 2020 (20A, 20B, and 20C). This study aimed to analyze the dif-fusion of SARS-CoV-2 in Spain using maximum-likelihood phylogenetic and Bayesianphylodynamic analyses. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated to have emerged in Wuhan, China, around 24 No-vember 2019. Phylogenetic analyses of the first 12,511 SARS-CoV-2 whole-genomesequences obtained worldwide, including 290 from 11 different regions of Spain, re-vealed 62 independent introductions of the virus in the country. Most sequencesfrom Spain were distributed in clades characterized by a D614G substitution in the Sgene (20A, 20B, and 20C) and an L84S substitution in ORF8 (19B) with 163 and 118sequences, respectively, with the remaining sequences branching in 19A. A total of110 (38%) sequences from Spain grouped in four different monophyletic clusters ofclade 20A (20A-Sp1 and 20A-Sp2) and 19B clade (19B-Sp1 and 19B-Sp2) along withsequences from 29 countries worldwide. The MRCAs of clusters 19A-Sp1, 20A-Sp1,19A-Sp2, and 20A-Sp2 were estimated to have occurred in Spain around 21 and 29January and 6 and 17 February 2020, respectively. The prevalence of clade 19B inSpain (40%) was by far higher than in any other European country during the firstweeks of the epidemic, probably as a result of a founder effect. However, this vari-ant was replaced by G614-bearing viruses in April.In vitroassays showed an en-hanced infectivity of pseudotyped virions displaying the G614 substitution comparedwith those having D614, suggesting a fitness advantage of D614G.This work was partially supported by the Spanish AIDS Research Network (RIS), funded by Instituto de Salud Carlos III and co-funded by European Development Fund (ERDF) “A way to build Europe” (project RD16CIII/0002/0001) and by the COVID funding project “Coordinación de actividades de investigación en el CNM para realizar una respuesta integradora frente a la pandemia por el SARS-CoV-2 en España”from Instituto de Salud Carlos III (project COV20_00679, MPY 222-20).S