COVID-19, the first pandemic in the post-genomic era

Abstract

The scale of the international efforts to sequence SARS-CoV-2 genomes is unprecedented. Early availability of genomes allowed rapid characterisation of the virus, thus kickstarting many highly successful vaccine development programmes. Worldwide genomic resources have provided a good understanding of the pandemic, supported close monitoring of the emergence of viral genomic diversity and pinpointed those sites to prioritise for functional characterisation. Continued genomic surveillance of global viral populations will be crucial to inform the timing of vaccine updates so as to pre-empt the spread of immune escape lineages. While genome sequencing has provided us with an exceptionally powerful tool to monitor the evolution of SARS-CoV-2, there is room for further improvements in particular in the form of less heterogeneous global surveillance and tools to rapidly identify concerning viral lineages.

Graphical abstract

Figure 1

Cumulative number of genome submissions to NCBI virus for major human viral pathogens for which genomic surveillance has been deployed. Data for SARS-CoV-2 is obtained from the GISAID data sharing repository. Y-axis provides the log10(cumulative number of genomes) and the x-axis provides the date of sample collection spanning from 1982 until the time of writing (June 2021). Lines are smoothed based on observations per year.

Figure 2

(a) Daily counts of genome assemblies (y-axis) shared on GISAID (current to 5/7/2021) over the course of the pandemic for all NextStrain clades. Note 20I (Alpha, V1) is broadly equivalent to PANGO lineage B.1.1.7, 20H (Beta, V2) to B.1.351, 20J (Gamma, V3) to P.1. and 21A (Delta) to B.1.617.2. (b) Equivalent plots as (a) split on each SARS-CoV-2 clade providing the daily proportions (y-axis) of genome submissions. Colour assignments for each clade are given as per the legend at bottom right.

Figure 3

Major mutations of interest along the SARS-CoV-2 genome. Line markers provide placement of mutations discussed in the text with the zoom box highlighting spike mutations. VoCs (defined current to May 2021) are highlighted for their carriage of major discussed mutations and deletions (* deletion; ◼ SNP), demonstrating striking patterns of convergent evolution. Note Public Health England additionally classify Alpha + E484K as a VoC. Major Variants of Interest (VoIs) at the time of writing include B.1.427 and B.1.429 (first detected in California and initially classified as VoCs by the Centers for Disease Control and Prevention; S:L452R). B.1.526 (first detected in New York; S:E484K + NSP6:del3675/3677), P.2 (first detected in Brazil; S:E484K), P.3 (first detected in the Philippines; S:E484K + S:N501Y), B.1.525 (detected in UK/Nigeria; NSP6:del3675/3677, S:del69/70, S:del144/145, S:E484K) and B.1.617.1 and B.1.617.3 (detected in India; S:452R, SE484Q, P681R). The bottom panel provides the density distribution of the count of recurrent mutations, over a 200-nucleotide sliding window, in the SARS-CoV-2 genome. The y-axis provides the number of estimated emergences based on a curated phylogeny of 550,743 sequences dating to April 2021 [25].