SARS-CoV-2 variants
Since the genome sequence of SARS-CoV-2 was first reported in January 2020, thousands of variants have been reported, the vast majority of which have not raised alarm from virologists and public health officials. However, three variants have arisen in the past few months that are cause for concern and have been designated Variants of Concern (VOC).
The three variants of concern – designated by their lineages – are: B.1.1.7, which emerged in September in England; B.1.351 first detected in South Africa in December 2020 and; the P.1 variant in Brazil, first detected in Japan in January in four people who had arrived in Tokyo following a visit to Amazonas, Brazil four days earlier. It was subsequently found to be circulating in Brazil.
There are other variants that are being investigated. For example, one detected in New York, called B.1.526 and one from Finland, called Fin-796H. These are reported to have mutations similar to B.1.1.7 and B.1.351.
According to the PANGO lineages database [1], as of 31 March the B.1.1.7 variant had been reported in 114 countries, the B.1.351 in 68 countries and the P.1 variant in 36 countries.
As with the unprecedented volume of SARS-CoV-2 research since the pandemic began, there have already been numerous studies published about the variants.
A matched cohort study by R. Challen et al published 10 March 2021 in The BMJ [2] finds that the British variant B.1.1.7 (also referred to as VOC-202012/1) significantly increases the risk of mortality compared with previously circulating SARS-CoV-2 variants. The authors warn that “if this finding is generalisable to other populations infection with VOC-202012/1 has the potential to cause substantial additional mortality compared with previously circulating variants”.
The B.1.1.7 variant has also been correlated with a significant increase in the rate of COVID-19 infection in United Kingdom, associated partly with the N501Y mutation. Studies of the variant lineage B.1.351 show that it is significantly more transmissible than previously circulating variants. Researchers noted that the variant contains several mutations that allow it to attach more easily to human cells because of the following three mutations in the receptor-binding domain (RBD) in the spike glycoprotein of the virus: N501Y, K417N, and E484K.
The N501Y mutation denotes a change from asparagine (N) to tyrosine (Y) in amino-acid position 501. This change is believed to increase binding affinity because of its position inside the spike glycoprotein’s RBD, which binds to ACE2 (Angiotensin-converting enzyme 2) receptors in human cells.
In addition, clinical trials indicate that many vaccines developed for the initial strain have lower efficacy for some variants against symptomatic COVID-19.
One study indicated that the Oxford-AstraZeneca vaccine had an efficacy of 42-89% against the B.1.1.7 variant, versus 71-91% against non-B.1.1.7 variants [3]. Preliminary data from a clinical trial indicated that the Novavax vaccine was 96% effective for symptoms against the original variant, 86% against B.1.1.7, and just 60% against the B.1.351 variant [4].
According to The BMJ, Pfizer and Oxford-AstraZeneca are reported to be in discussions regarding updating their vaccines to target new variants. And, Moderna has just started a trial of a modified version of its vaccine that will target the B.1.351 variant.
Potential consequences of emerging variants • Increased transmissibility
- Increased morbidity
- Increased mortality
- Ability to evade detection by diagnostic tests
- Decreased susceptibility to antiviral drugs (if and when such drugs are available)
- Decreased susceptibility to neutralizing antibodies, either therapeutic (e.g., convalescent plasma or monoclonal antibodies) or in laboratory experiments
- Ability to evade natural immunity (e.g., causing reinfections)
- Ability to infect vaccinated individuals
- Increased risk of particular conditions such as multisystem inflammatory syndrome or long-haul COVID.
- Increased affinity for particular demographic or clinical groups, such as children or immunocompromised individuals.
References
- PANGO – https://cov-lineages.org/global_report.html
- Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort . 2021; 372 doi: https://doi.org/10.1136/bmj.n579
- Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7). SSRN Electronic Journal. https://doi.org/10.2139/ssrn.3779160.
- “COVID-19: Novavax vaccine efficacy is 86% against UK variant and 60% against South African variant”. BMJ. 372: n296. https://doi.org/10.1136/bmj.n296
- “Emerging SARS-CoV-2 Variants”. https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/scientific-brief-emerging-variants.html
