Distinct mutations and lineages of SARS-CoV-2 virus in the early phase of COVID-19 pandemic and subsequent global expansion

A novel coronavirus, SARS-CoV-2, has caused over 85 million cases and over 1.8 million deaths worldwide since it occurred twelve months ago in Wuhan, China. Here we conceptualized the time-series evolutionary and expansion dynamics of SARS-CoV-2 by taking a series of cross-sectional view of viral genomes from early outbreak in January in Wuhan to early phase of global ignition in early April, and finally to the subsequent global expansion by late December 2020. By scrutinizing cases from early outbreak, we found a viral genotype from the Seafood Market in Wuhan featured with two concurrent mutations has become the overwhelmingly dominant genotype (95.7%) of the pandemic. By analyzing 4,013 full-length SARS-CoV-2 genomes from different continents by early April, we were able to visualize the genomic diversity over a 14-week timespan since the outbreak in Wuhan. 2,954 unique nucleotide substitutions were identified with 31 of the 4,013 genomes remaining as ancestral type, and 952 (32.2%) mutations recurred in more than one genome. 11 major viral genotypes with unique geographic distributions were identified. As the pandemic has been unfolding for more than one year, we also used the same approach to analyze 261,323 full-length SARS-CoV-2 genomes from the world since the outbreak in Wuhan (i.e. including all the available viral genomes in the GISAID database as of 25 December 2020) in order to recapitulate our findings in a real-time fashion and to present a full catalogue of SARS-CoV-2 mutations. We demonstrated the viral genotypic dynamics from different geographic locations over one-year timespan reveal transmission routes and indicate subsequent expansion. This study, to our knowledge, is heretofore the largest and most comprehensive genomic study of SARS-CoV-2. It indicates the viral genotypes can be utilized as molecular barcodes in combination with epidemiologic data to monitor the spreading routes of the pandemic and evaluate the effectiveness of control measures. Moreover, the dynamics of viral mutational spectrum in the study may help the early identification of new strains in patients to reduce further spread of infection, and guide the development of molecular diagnosis and vaccines against COVID-19, and last but not the least help assess their accuracy and efficacy. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAs the COVID-19 pandemic continues, in order to mitigate the risk of further regional expansions as well as to estimate the effectiveness of control measures in various regions, viral genomic studies on its origins, transmission routes and expansion models have begun to surge. Several studies on the genomics of SARS-CoV-2 virus have offered clues of the origins, and transmission path of the disease. However, due to lack of early samples, a limited number of SARS-CoV-2 genomes, and/or focusing on specific geographic locations, we still lack a complete global view of the expansion of COVID-19 in the context of the viral mutational spectrum. Added value of this studyIn this study we provide a global view of the mutation dynamic and transmission routes of SARS-CoV-2 with a foothold on the early phase of the pandemic. This is also the largest and the most comprehensive SARS-CoV-2019 viral genome study and molecular epidemiology study that provides an unprecedented time window to study mutations and evolution of SARS-CoV-2. The unique molecular barcodes defined by Strain of Origin (SOO) algorithm can be utilized to prospectively monitor the spreading trajectory and reveal the expansion of the ongoing pandemic. Our full catalogue of SARS-CoV-2 mutations can also guide the development and help assess the accuracy of molecular diagnosis and the efficacy of the vaccines against COVID-19. Implications of all the available evidenceThe results that we presented here serve as a proof of concept to demonstrate the utility of large-scale viral genome sequencing during a novel pathogen outbreak. Ramping up sampling in a real-time manner may generate high-resolution maps of who-infected-whom transmission at community level and reveal the subsequent expansion patterns which are especially crucial for the most severely stricken countries and regions to promptly develop tailored mitigation plans.