COVID-19 Variants


Viruses and Variants

A virus is a genetic code (DNA or RNA) enveloped in a lipid and protein capsule. Unlike other living things, viruses cannot replicate alone; they require host cells. In order to infect host cells viruses have various adaptations to allow penetration into the host cell. For example in the case of SARS-CoV-2, there are multiple spikes with receptors and enzymes allowing for binding to, and penetration into, the host cell. Once within the host cell, the virus can then replicate, usually killing the host cell in the process, and causing physical manifestations of disease. Viruses cannot be killed by antibiotics, vaccines and anti-viral medications are the only pharmaceutical methods to reduce viral disease.

Viruses constantly mutate into new forms, or variants. A variant is any change in the DNA or RNA sequence of a virus. Using a fruit analogy, think of the variety of apples. Red Delicious, Granny Smith, and Honeycrisp are “variants” of apples. With infectious diseases, some variants are harmful, and some have no effect. A vast array of possible effects exist, including increased transmissibility, increased lethality, immune escape, and more.

Variants are detected through genomic analysis when test samples are obtained from patients. The DNA from the patient’s sample is compared to the DNA of other samples looking for differences or variances.

The COVID-19 variants are categorized into Variant of Interest (VOI), Variant of Concern (VOC), and Variant of High Consequence (VOHC).

COVID-19 Variants

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Several variants have already been identified, and more may emerge. Some of the variants spread more easily (increased transmissibility), and some have resistance to certain vaccines. Because the situation is evolving rapidly much remains unknown while scientists continue to investigate.

Several new variants have been identified, some of which have been classified as "global concern" by the World Health Organization (WHO). On 31 May 2021, the WHO established a naming convention based on letters of the Greek Alphabet. Media and other reporting agencies sometimes label these by the geographical area where they were first discovered, where previously it was more accurate to classify them by their lineage numbers. The Alpha lineage is B.1.1.7 (first identified in the United Kingdom), Beta is B.1.351 (first identified in South Africa) , Gamma is P.1, in the B.1.1.28 lineage (first identified in Brazil) and Delta is B.1.617.2 (first identified in India).

As more and more locations are undertaking genetic sequencing of SARS-CoV-2, more variants will be identified. It is expected some may be more transmissible, potentially cause more severe disease (lethality), and / or evade current vaccinations (immune escape). (a project at Scripps Research supported by the National Institute for Allergy and Infectious Diseases, National Center for Data to Health, and Centers for Disease Control and Prevention) has a dashboard of variants. The dashboard allows customisable reports by variant, location and time.

What are the concerns about the variant strains?

Different variants have different mutations, each of which can have a different effect. A single variant may contain multiple mutations compared to its parent. Because the situation is continuing to evolve rapidly, and more variants are expected to emerge, there are a number of concerns due to the unknowns. Mutations can alter transmissibility and severity, as well as cause resistance to medications and immune escape (resistance to vaccine). Other unknowns exist as well, such as the impact on those with pre-existing conditions.

Numerous mutations have been identified, with N501Y and E484K being among the most well known. The N501Y mutation increases transmissibility, and is a defining mutation in several lineages. The E484K mutation is present in several variants and increases immune escape by altering the spike protein.

Will the vaccines be effective against the new variants?

Vaccination produces a ‘polyclonal’ response that targets several parts of the spike protein. The virus would likely need to accumulate multiple mutations in the spike protein to evade immunity induced by a vaccine. According to the CDC, “So far, studies suggest that antibodies generated through vaccination with currently authorized vaccines recognize these variants. This is being closely investigated and more studies are underway.” If, as ascertained by preliminary studies, neutralizing function is indeed diminished but not eliminated, then it could suggest that a strong vaccine response will protect against the variant. However, as noted below, certain vaccines have reduced efficacy against specific variants.

The European Centres for Disease Control and Prevention (ECDC) have also stated: "The COVID-19 vaccines that are currently being rolled out through vaccination programmes are expected to provide at least some protection against new virus variants because they all lead to a broad immune response. If any of these vaccines prove to be less effective against one or more variants, it will be possible to change the composition of the vaccine to protect against those variants."

Regardless, it is vital for communities to have rigorous compliance with non-pharmaceutical interventions in addition to getting vaccinated.

Specific Variants & Their Characteristics

Delta: B.1.617.2 | 20A | “Indian variant”

The B.1.617 variant was first identified in India and has spread to several other countries. Several sub-lineages have since been identified, including Beta (B.1.617.2) - a Variant of Concern and Kappa (B.1.617.1) - a Variant of Interest. Updated locations where it has been detected may be found here. This variant has increased transmissibility, and multiple mutations to the spike protein, including E484Q, and L452R. It does not have the N501Y mutation. This variant has not officially been associated with India by the WHO, so some officials have recommended against using the name "Indian variant" despite this term entering popular vocabulary.

Alpha: B.1.1.7 | 20I | 501Y.V1 | “UK variant”

This variant was first identified in the United Kingdom in September 2020 and is classified as a Variant of Concern. Emerging evidence indicates this strain can result in more severe COVID-19 disease. While initially there was no evidence of more severe disease, more recent reports indicate that this variant can lead to a increase in hospitalization and death. B.1.1.7 is associated with increased transmissibility (i.e., more efficient and rapid transmission), approximately 36-70%.

This variant has a mutation in the receptor binding domain (RBD) of the spike protein at position 501, where the amino acid asparagine (N) has been replaced with tyrosine (Y). The shorthand for this mutation is N501Y.

Existing public health and social preventative measures work as well for this variant as they do for previous strains. A study published 20 May 2021 in The New England Journal of Medicine, noted that the AstraZeneca vaccine has 75% efficacy against this variant.

However, as this is a more easily transmissible variant, it is essential that correct wearing of masks, cough etiquette, handwashing and physical distancing are rigorously and continually applied. Similarly, it is more important than ever to avoid crowded environments, particularly bars or clubs, where there is limited ventilation and mask-wearing is reduced.

Vaccine Efficacy

Several Vaccine-producing companies (Pfizer-BioNTech, Moderna, AstraZeneca-Oxford, Johnson and Johnson, Novavax) have confirmed that their vaccines, based on different designs, can all be effective against this variant. As an example, the Novavax vaccine has shown an efficacy of 89.3% in its Phase 3 clinical trial conducted in the UK. It has also shown some immune escape, with studies finding the Novavax efficacy decreased from 96% to 86%. Interestingly, a study published in The New England Journal of Medicine found the Oxford/AstraZeneca vaccine is approximately 75% effective against the B.1.1.7 variant. This is in comparison to the overall efficacy prior to the emergence of the B.1.351 and P.1 variants, measured at 66.7%. The same study found that the mRNA vaccines (Pfizer/BioNTech and Moderna), had no reduced efficacy.

Diagnostic Efficacy

The current molecular tests detect most of the variants and thus are able to diagnose COVID-19 infection by such variants. Yet, the fine identification of the type of variants is still based on sequence analysis although multiplex PCR tests are being evaluated.

Beta: B.1.351 | 20H | 501Y.V2 | VOC 202012/02 | “South African variant”

Another Variant of Concern, first identified in South Africa. The N501Y and E484K mutations are both present, among others. Some evidence has shown 50% greater transmissibility, but so far there is no evidence of increased severity.

Vaccine Efficacy

This strain has significantly reduced efficacy to the Oxford/AstraZeneca vaccine. A study published in The New England Journal of Medicine found the Oxford/AstraZeneca vaccine “did not show protection against mild to moderate COVID-19 due to the B.1.351 variant.” The same study noted interim results found the Janssen vaccine to be 57% effective against moderate to severe COVID-19 and 89% effective against severe cases.

The Sputnik V vaccine has reduced efficacy, and one study found Novavax had 60% efficacy in adults that are HIV negative.

Gamma: P.1 | 20J | 501Y.V3 | “Brazil variant”

First noted in travelers from Brazil, this variant has multiple mutations to the spike protein including N501Y. It is likely that some vaccines will have reduced efficacy against this variant, but studies are ongoing, and there is no established evidence yet. The effects of bamlanivimab and etesevimab are significantly reduced against this variant, and it has shown reduced neutralization by convalescent plasma.


bioRxiv preprint doi: version posted January 4th, 2021