Massive dissemination of a SARS-CoV-2 Spike Y839 variant in Portugal

Emerg Microbes Infect. 2020 Dec;9(1):2488-2496. doi: 10.1080/22221751.2020.1844552.

Abstract

Genomic surveillance of SARS-CoV-2 was rapidly implemented in Portugal by the National Institute of Health in collaboration with a nationwide consortium of >50 hospitals/laboratories. Here, we track the geotemporal spread of a SARS-CoV-2 variant with a mutation (D839Y) in a potential host-interacting region involving the Spike fusion peptide, which is a target motif of anti-viral drugs that plays a key role in SARS-CoV-2 infectivity. The Spike Y839 variant was most likely imported from Italy in mid-late February and massively disseminated in Portugal during the early epidemic, becoming prevalent in the Northern and Central regions of Portugal where it represented 22% and 59% of the sampled genomes, respectively, by 30 April. Based on our high sequencing sampling during the early epidemics [15.5% (1275/8251) and 6.0% (1500/24987) of all confirmed cases until the end of March and April, respectively], we estimate that, between 14 March and 9 April (covering the epidemic exponential phase) the relative frequency of the Spike Y839 variant increased at a rate of 12.1% (6.1%-18.2%, CI 95%) every three days, being potentially associated with 24.8% (20.8-29.7%, CI 95%; 3177-4542 cases, CI 95%) of all COVID-19 cases in Portugal during this period. Our data supports population/epidemiological (founder) effects contributing to the Y839 variant superspread. The potential existence of selective advantage is also discussed, although experimental validation is required. Despite huge differences in genome sampling worldwide, SARS-CoV-2 Spike D839Y has been detected in 13 countries in four continents, supporting the need for close surveillance and functional assays of Spike variants.

Keywords: COVID-19; D839Y; SARS-CoV-2; Spike; fusion peptide; genetic variant; genomic epidemiology; mutation.

MeSH terms

  • COVID-19 / diagnosis
  • COVID-19 / epidemiology*
  • COVID-19 / transmission*
  • COVID-19 / virology
  • Epidemiological Monitoring
  • Genome, Viral*
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation*
  • Pandemics*
  • Phylogeny
  • Portugal / epidemiology
  • SARS-CoV-2 / classification
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / isolation & purification
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / genetics*

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Grants and funding

This study is co-funded by Fundação para a Ciência e a Tecnologia and Agência de Investigação Clínica e Inovação Biomédica [grant number 234_596874175] on behalf of the Research 4 COVID-19 call. This work is also a result of the GenomePT project [grant number POCI-01-0145-FEDER-022184], supported by COMPETE 2020 – Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).