Phylogeography of SARS-CoV-2 pandemic in Spain: a story of multiple introductions, micro-geographic stratification, founder effects, and super-spreaders

Zool Res. 2020 Nov 18;41(6):605-620. doi: 10.24272/j.issn.2095-8137.2020.217.

Abstract

Spain has been one of the main global pandemic epicenters for coronavirus disease 2019 (COVID-19). Here, we analyzed >41 000 genomes (including >26 000 high-quality (HQ) genomes) downloaded from the GISAID repository, including 1 245 (922 HQ) sampled in Spain. The aim of this study was to investigate genome variation of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and reconstruct phylogeographic and transmission patterns in Spain. Phylogeographic analysis suggested at least 34 independent introductions of SARS-CoV-2 to Spain at the beginning of the outbreak. Six lineages spread very successfully in the country, probably favored by super-spreaders, namely, A2a4 (7.8%), A2a5 (38.4%), A2a10 (2.8%), B3a (30.1%), and B9 (8.7%), which accounted for 87.9% of all genomes in the Spanish database. One distinct feature of the Spanish SARS-CoV-2 genomes was the higher frequency of B lineages (39.3%, mainly B3a+B9) than found in any other European country. While B3a, B9, (and an important sub-lineage of A2a5, namely, A2a5c) most likely originated in Spain, the other three haplogroups were imported from other European locations. The B3a strain may have originated in the Basque Country from a B3 ancestor of uncertain geographic origin, whereas B9 likely emerged in Madrid. The time of the most recent common ancestor (TMRCA) of SARS-CoV-2 suggested that the first coronavirus entered the country around 11 February 2020, as estimated from the TMRCA of B3a, the first lineage detected in the country. Moreover, earlier claims that the D614G mutation is associated to higher transmissibility is not consistent with the very high prevalence of COVID-19 in Spain when compared to other countries with lower disease incidence but much higher frequency of this mutation (56.4% in Spain vs. 82.4% in rest of Europe). Instead, the data support a major role of genetic drift in modeling the micro-geographic stratification of virus strains across the country as well as the role of SARS-CoV-2 super-spreaders.

西班牙曾经是新型冠状病毒肺炎(COVID-19)全球大流行的中心之一。本研究我们分析了从GISAID数据库上获取超过4100个病毒基因组(包括超过2600个高质量的基因组),其中包含了在西班牙采样的1245个基因组(922个高质量基因组)。这项研究的主要目的是分析SARS-CoV-2病毒的基因组变异情况,并重建西班牙病毒的谱系地理和传播模式。谱系地理分析表明,从疫情爆发开始SARS-CoV-2在西班牙至少有34次独立传入事件,其中6个谱系毒株非常成功地在西班牙传播,也就是六个超级传播者,A2a4型(7.8%),A2a5型(38.4%),A2a10型(2.8%),B3a型(30.1%)和B9型(8.7%)毒株所造成,这些毒株数据占西班牙所有基因组的87.9%。西班牙流行的SARS-CoV-2基因组中有一个独特B型谱系(39.3%,主要是B3a+B9型)毒株,其发生频率远高于其它任何欧洲国家。研究推测B3a型,B9型(以及A2a5型的一个重要衍生谱系,即A2a5c型)毒株最有可能起源于西班牙,其它三个单倍型毒株可能是由从其他欧洲地区输入。B3a谱系毒株可能起源于巴斯克地区,由一个地理来源不确定的B3祖先毒株衍生而来,而B9谱系毒株则可能来源于马德里。基于估算西班牙国内检测到的第一个谱系B3a最近共同祖先(TMRCA)分化时间,推测出第一批病毒输入西班牙的时间大约在2020年2月11日。此外,对比其他疾病发病率较低但D614G突变发生率更高的国家(西班牙56.4%对比欧洲其他地区82.4%),早先的说法是D614G突变体与较高的传播能力相关,但这与西班牙COVID-19的高流行并不相符。相反,这些数据支持遗传漂变在模拟病毒株微地理尺度下分区的主要作用,以及SARS-CoV-2超级传播者在传播病毒中的作用。.

Keywords: Covid-19; Genomics; Phylogeny; Phylogeography; SARS-CoV-2.

MeSH terms

  • Animals
  • Betacoronavirus / classification
  • Betacoronavirus / genetics*
  • Betacoronavirus / physiology
  • COVID-19
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / transmission*
  • Coronavirus Infections / virology
  • Evolution, Molecular
  • Founder Effect
  • Genetic Variation*
  • Genome, Viral / genetics*
  • Geography
  • Haplotypes
  • Humans
  • Mutation
  • Pandemics
  • Phylogeny
  • Phylogeography
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / transmission*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Spain / epidemiology

Grants and funding

This study was supported by the Instituto de Salud Carlos III: project GePEM (Instituto de Salud Carlos III(ISCIII)/PI16/01478/Cofinanciado FEDER), DIAVIR (Instituto de Salud Carlos III(ISCIII)/DTS19/00049/Cofinanciado FEDER; Proyecto de Desarrollo Tecnológico en Salud) and Resvi-Omics (Instituto de Salud Carlos III(ISCIII)/PI19/01039/Cofinanciado FEDER) and project BI-BACVIR (PRIS-3; Agencia de Conocimiento en Salud (ACIS)—Servicio Gallego de Salud (SERGAS)—Xunta de Galicia; Spain) given to A.S.; and project ReSVinext (Instituto de Salud Carlos III(ISCIII)/PI16/01569/Cofinanciado FEDER) and Enterogen (Instituto de Salud Carlos III(ISCIII)/ PI19/01090/Cofinanciado FEDER) given to F.M.-T.