Evolution of the viral genomes of SARS-CoV-2 in association with the changes in local condition: a genomic epidemiological study of a suburban city of Japan

Understanding the factors driving the spread and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the local, regional, national, and international levels is important in protecting against future pandemics. By exploring their viral genomes, we attempted to analyse the spread of SARS-CoV-2 and its evolutionary convergence in Kashiwa City, as an example of a representative commuter town in Japan. From September 2020 to January 2023, a total of 47,134 nasopharyngeal swab and saliva specimens were collected from patients in 47 local clinics and hospitals, covering the vast majority of healthcare facilities. All SARS-CoV-2-positive samples were subjected to whole genome sequencing. Based on the analysis of 5,536 identified genomes, all major strains were represented. Unique regional mutations were occasionally identified in each strain. Inspection of these mutations revealed that the overall base substitution rate increased with progressive waves of the pandemic, at an overall rate of 2.56 bases/year. Interestingly, the spread and evolutionary patterns appeared to be distinct between regions and between individual clinics. Further analysis of the synonymous base substitution rate showed that the speed of viral evolution accelerated coincident with the beginning of public vaccination. Comprehensive genomic epidemiological studies, as presented here, should be useful in precisely understanding the pandemic and preparing for possible future pandemics.