COVID-19 Variants -What Do They Mean?
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.
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 has been detected in England, South Africa, Brazil 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.
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Consequently, it is helpful to understand the nomenclature of a changing genome:
- Mutation is any substitution in a nucleotide within genome sequence
- can result in an amino acid change in protein synthesis
- can be neutral without affecting the protein structure
- Variant describes a group of viruses with change in the genomic sequence
- can involve a single mutation or many mutations
- Strain is used to describe a variant that imparts a phenotypic change in a virus
- transmissibility
- virulence (higher morbidity or mortality)
- antigenicity
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.
- UK (B.1.1.7) appears to have emerged with
a large number of mutations in southeastern UK and has spread rapidly,
implying heightened levels of transmissibility.
- South Africa (1.351-3) has
multiple mutations in the spike protein, the antigenic basis for current
vaccines.
- Brazil (P.1) emerged with 17 unique
mutations, including three in the receptor-binding domain of the spike
protein.
- India (B.1.617) the Indian variant consists of two mutations on the spike protein of
the virus. The mutations found
in the Indian variant are identified as E484Q and L452. Indian variant has
spread to Germany, Belgium, the United Kingdom, Switzerland, the
United States, Australia and Singapore. Indian variant may be turning into a type of "super
mutation" that will continue to spread across the world.
This type of
mutation therefore allows Sars-CoV-2 to slip past the first line of
immunological defense in people who have been vaccinated or previously
infected, enabling the virus to carry on circulating.
- Lauring AS, Hodcroft EB. Genetic variants of SARS-CoV-2—what do they mean? [published online ahead of print, 2021 Jan 6]. JAMA. 2021 Jan 6. doi: 10.1001/jama.2020.27124. Online ahead of print. https://jamanetwork.com/journals/jama/fullarticle/2775006
- CDC. Emerging SARS-CoV-2 variants. Updated January 15, 2021. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.htm
- https://www.practiceupdate.com/c/111993/75/24/
- https://www.dw.com/en/the-covid-variant-from-india-what-we-know-so-far/a-57313664
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