Host-dependent editing of SARS-CoV-2 in COVID-19 patients

Emerg Microbes Infect. 2021 Dec;10(1):1777-1789. doi: 10.1080/22221751.2021.1969868.


A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.

Keywords: ADAR1; SARS-CoV-2; editing; mutations; quasispecies.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • COVID-19 / virology*
  • Female
  • Genetic Variation*
  • Host-Pathogen Interactions
  • Humans
  • Male
  • Middle Aged
  • Protein Conformation
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / physiology
  • Spike Glycoprotein, Coronavirus / genetics*
  • Virus Replication


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

Grants and funding

This study was supported by the Direcció General de Recerca i Innovació en Salut (DGRIS) of the Catalan Health Ministry, Generalitat de Catalunya, through the Vall d’Hebron Institut de Recerca (VHIR); the European Regional Development Fund (ERDF) “A way to achieve Europe” by the Spanish Network for Research in Infectious Diseases [grant number REIPI RD16/0016/0003]; Instituto de Salud Carlos III [grant number FIS PI19/00301]; and Centro para el Desarrollo Tecnologico Industrial (CDTI) from the Ministry of Economic Affairs and Digital Transformation [grant number IDI-20200297].