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. 2023 Nov 23;78(Suppl 2):ii25-ii36.
doi: 10.1093/jac/dkad309.

SARS-CoV-2 genomics and impact on clinical care for COVID-19

Affiliations

SARS-CoV-2 genomics and impact on clinical care for COVID-19

Ramon Lorenzo-Redondo et al. J Antimicrob Chemother. .

Abstract

The emergence and worldwide spread of SARS-CoV-2 during the COVID-19 pandemic necessitated the adaptation and rapid deployment of viral WGS and analysis techniques that had been previously applied on a more limited basis to other viral pathogens, such as HIV and influenza viruses. The need for WGS was driven in part by the low mutation rate of SARS-CoV-2, which necessitated measuring variation along the entire genome sequence to effectively differentiate lineages and characterize viral evolution. Several WGS approaches designed to maximize throughput and accuracy were quickly adopted by surveillance labs around the world. These broad-based SARS-CoV-2 genomic sequencing efforts revealed ongoing evolution of the virus, highlighted by the successive emergence of new viral variants throughout the course of the pandemic. These genomic insights were instrumental in characterizing the effects of viral mutations on transmissibility, immune escape and viral tropism, which in turn helped guide public health policy, the use of monoclonal antibody therapeutics and vaccine development strategies. As the use of direct-acting antivirals for the treatment of COVID-19 became more widespread, the potential for emergence of antiviral resistance has driven ongoing efforts to delineate resistance mutations and to monitor global sequence databases for their emergence. Given the critical role of viral genomics in the international effort to combat the COVID-19 pandemic, coordinated efforts should be made to expand global genomic surveillance capacity and infrastructure towards the anticipation and prevention of future pandemics.

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Figures

Figure 1.
Figure 1.
Viral genetic diversity is the basis of natural selection and viral evolution. All viruses mutate over time. Mutations that are disadvantageous or that come at a cost to viral fitness are selected against. Mutations that confer a fitness advantage, especially in the presence of a selective pressure (represented by the horizontal dotted line), will be more likely to persist in future generations. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
Figure 2.
Figure 2.
Different SARS-CoV-2 ORFs have accumulated different amounts of variability. (a) Schematic of the SARS-CoV-2 genome and encoded proteins, separated broadly in the figure by function. (b) Entropy (a measure of genetic variability) in each SARS-CoV-2 ORF. Dot size and colour reflect the degree of entropy accumulated in the viral population since its emergence. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
Figure 3.
Figure 3.
Workflow diagram comparing metagenomic, amplicon-based and target capture strategies for pathogen genomics. The pie charts at the end depict the theoretical yield of pathogen sequence versus host or non-specific background. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.
Figure 4.
Figure 4.
The ongoing evolution of SARS-CoV-2. (a) Phylogenetic tree of representative consensus sequences for globally prominent SARS-CoV-2 clades and variants of concern (Alpha, Beta, Gamma, Delta, and Omicron). (b) Cumulative frequency plot of globally prominent SARS-CoV-2 clades and variants of concern from December 2019 to February 2023. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

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    Cunningham N, Hopkins S. Cunningham N, et al. J Antimicrob Chemother. 2023 Nov 23;78(Suppl 2):ii43-ii49. doi: 10.1093/jac/dkad310. J Antimicrob Chemother. 2023. PMID: 37995355 Free PMC article.

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