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Genetic Variants of SARS-CoV-2
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This viewpoint reviews pathophysiology of viral mutation and clinical consequences associated with the SARS-CoV-2 pandemic. Mutations naturally arise during viral replication and can spread due to natural selection (if a new phenotype confers a competitive advantage) or due to chance (such as the founder effect). Initial variations in the spike protein sequence have been associated with increased viral transmissibility, although also were detected early enough to have been perpetuated due to the founder effect. More recently, a new series of mutations termed lineage B.1.1.7 has been detected in England and is associated with more rapid viral spreading. The currently approved COVID-19 vaccines induce an antibody response to the entire spike protein, so it is anticipated that the vaccine should remain effective against all of these variants.
- This paper provides a clinically relevant overview of viral mutation and its clinical significance in the COVID-19 pandemic.
abstract
This abstract is available on the publisher's site.
Access this abstract nowOver the course of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the clinical, scientific, and public health communities have had to respond to new viral genetic variants. Each one has triggered a flurry of media attention, a range of reactions from the scientific community, and calls from governments to either “stay calm” or pursue immediate countermeasures. While many scientists were initially skeptical about the significance of the D614G alteration, the emergence of the new “UK variant”—lineage B.1.1.7—has raised widespread concern. Understanding which variants are concerning, and why, requires an appreciation of virus evolution and the genomic epidemiology of SARS-CoV-2.
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Genetic Variants of SARS-CoV-2-What Do They Mean?
JAMA 2021 Jan 06;[EPub Ahead of Print], AS Lauring, EB HodcroftFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Primary Care
SARS-CoV-2 Variants and Why They Matter
Primary care clinicians receive a confusing array of messages regarding variants and new strains of SARS-CoV-2. It is worthwhile to step back and first review what is meant by genetic variants and why these variants matter. A very concise overview has been provided by Lauring and Hodcroft.1 In addition, think back to those early biology courses and remember that mutation within a genome is the rule and not the exception, and that rates of change are governed by internal (biochemical) and external (selection) processes.
Coronaviruses—by the very nature of their RNA-based genome—have an intrinsically higher rate of mutation than DNA-based viruses. That said, they manifest a lower rate of mutation than influenza viruses due to the presence of genetic code for an enzyme that corrects some transcription errors. Consequently, it is helpful to understand the nomenclature of a changing genome:
As variants arise, other forces come into play. Arriving in a population with high susceptibility, there can be the “founder effect,” wherein the variant takes off as the only virus around. Natural selection can favor viruses with higher transmissibility, or the ability to escape from existing host immunity. Purifying selection results in the removal of mutations that are deleterious in hosts.
In primary care medicine and public health, we are mostly concerned about those strains that have the potential to be more transmissible, have higher virulence, or alter the immune response gained from previous infection or vaccination. Three strains have come under great scrutiny of late and require our continued vigilance.2 In addition, all three have now been identified in the United States:
Stay tuned.
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