Live Science 10 July 2021
Several strains of SARS-CoV-2, the coronavirus causing the disease COVID-19, have emerged across the globe. Viruses mutate all the time, so these new variations were not surprising; however, when a modified version becomes a dominant strain in a region or one with worrisome features, public health experts name and follow those versions. Many of the so-called SARS-CoV-2 mutants show modifications to the virus's spike protein — which the virus uses to latch onto and invade human cells. As such, the various genetic mutations have in some cases increased transmissibility and even possibly severity of illness associated with those particular variants. Here's a look at the science behind SARS-CoV-2 variants and which ones are the most concerning in different areas.
Variants of concern
Alpha variant (B.1.1.7)
What is the variant? The alpha variant, formerly called B.1.1.7, was first seen in the United Kingdom in September 2020, according to the World Health Organization (WHO). By December 2020, the variant had shown up in the United States.
Where is it? The variant has spread to at least 114 countries, according to the Global Virus Network, and it is responsible for about 95% of new COVID-19 infections in the U.K. Between May 23 and June 5, 2021, about 60% of the total cases in the U.S. were linked to the alpha variant, the CDC reported.
What are key mutations? The alpha variant has 23 mutations compared with the original Wuhan strain, with eight of those in the virus's spike protein, according to the American Society for Microbiology. (ASM) Three of the spike-protein mutations are thought to be responsible for the biggest impact on the virus's biology: The N501Y mutation seems to boost how tightly the spike protein attaches to the ACE2 receptors — the main entry point into human cells; the 69-70del mutation could, in concert with N501Y, explain the variant's increased transmissibility, some scientists say; and the P681H mutation could also increase transmissibility, as it may be involved in how the virus merges its membrane with that of a human cell in order to deliver its genome into the cell, according to the ASM.
Why is the variant concerning? The strain is about 50% more transmissible than the original form of the novel coronavirus, according to the Centers for Disease Control and Prevention (CDC). It also possibly causes more severe cases of COVID-19, the CDC said.
Do vaccines work? Research to date suggests that the two mRNA COVID-19 vaccines (also called the Pfizer and Moderna vaccines, respectively) are effective at preventing symptomatic infections with the alpha variant of the coronavirus. For instance, a study published June 28 in the journal Nature Communications found that the blood of health care workers who had been vaccinated with the Pfizer shot was effective at neutralizing B.1.1.7. A single dose of the Johnson & Johnson vaccine also stimulates neutralizing antibodies that protect against the alpha variant, J&J recently reported.
Beta variant (B.1.351)
What is the variant? The beta variant, formerly called B.1.351, was first detected in South Africa in May 2020 and was designated a variant of concern in December 2020, according to WHO.
Where is it? This variant has been detected in at least 48 countries and in 23 U.S. states, according to the Global Virus Network.
What are key mutations? The beta variant has eight distinct mutations that may affect how the virus binds to cells, Live Science previously reported. The most notable are N501Y, K417N and E484K. The N501Y mutation, also seen in the alpha variant, may allow the novel coronavirus to bind more tightly to the ACE2 receptor. The K417N mutation may change the shape of the spike protein, making antibodies primed for earlier strains less likely to recognize the spike. The third notable mutation, E484K, also seems to help the virus evade antibodies from the immune system, according to a February study in the British Medical Journal.
Why is the variant concerning? The beta variant is about 50% more transmissible than the original strain of SARS-CoV-2 that emerged in Wuhan, according to the CDC. Some monoclonal antibodies don’t work as well against the strain, according to the CDC. Vaccines are also less effective against the variant. And the variant may lead to slightly more severe disease and slightly higher risk of death than the original coronavirus, according to a July study in The Lancet Global Health.
Do vaccines work? Most vaccines work with lower efficacy against beta than was seen for earlier strains. For instance, the Pfizer vaccine has a 75% efficacy against the beta variant, which is lower than the 95% efficacy seen in clinical trials when earlier strains were dominant, according to a May 2021 study in The New England Journal of Medicine. The Johnson & Johnson and Novavax vaccines also showed lower efficacy against the beta variant. And the AstraZeneca vaccine did not prevent mild or moderate COVID-19 in trials in South Africa when beta was the dominant strain, according to the Global Virus Network. Data on how well the Moderna shot works against the beta variant is limited, but most experts suspect it will work similarly to Pfizer's mRNA vaccine.
Gamma variant (P.1)
What is the variant? The earliest documented samples of the gamma variant, also known as P.1, were collected in Brazil in November 2020, according to the WHO. Scientists first found the variant in Japan in early January 2021, when four travelers tested positive for the virus after a trip to Brazil; researchers then found evidence that the variant was already widespread in the South American country, The New York Times reported. Gamma was labeled as a variant of concern on Jan. 11, 2021.
Where is it? Gamma has been reported in 74 countries worldwide, according to the United Nations new site. First detected in the U.S. in January 2021, the variant has now been reported in at least 30 U.S. states, according to the CDC.
What are key mutations? Gamma is closely related to beta (B.1.351), and the two variants share some of the same mutations in their spike proteins, the Times reported. These spike protein mutations include N501Y, which helps the virus bind tightly to cells and is also found in the alpha (B.1.1.7) lineage. The spike mutation K417T may also help gamma latch onto cells, while the E484K mutation likely helps the variant dodge certain antibodies. And according to the CDC, in addition to these three mutations, the variant carries eight additional sequence changes in its spike: L18F, T20N, P26S, D138Y, R190S, D614G, H655Y and T1027I.
Why is the variant concerning? Several studies suggest that gamma is about twofold more transmissible than its parent coronavirus lineage, B.1.1.28, and that gamma infections are associated with a significantly higher viral load than other variants. Compared with the original strain of SARS-CoV-2, Gamma shows less susceptibility to several monoclonal antibody treatments, including bamlanivimab and etesevimab, according to the CDC. And according to a recent study, published May 12 in the journal Cell Host & Microbe, the variant also appears relatively resistant to neutralization by convalescent plasma and antibodies drawn from vaccinated people.
Do vaccines work? Moderna's COVID-19 vaccine produces neutralizing antibodies against gamma, although the shot is slightly less effective against the variant than it is against the original strain of the virus, the company announced on June 29. The Pfizer vaccine showed similar levels of protection against gamma in a recent study, Business Insider reported; and the single-dose Johnson & Johnson vaccine also produces neutralizing antibodies against the variant, according to a recent statement from the company.
Delta variant (B.1.617.2)
What is the variant? The delta variant, formerly called B.1.617.2, was first identified in India in October 2020 and labeled as a variant of concern in May 2021, according to the WHO.
Where is it? The fast-spreading variant has been detected in more than 100 countries and is rapidly becoming the dominant strain around the world. Delta is currently displacing alpha in the U.S.; as of July 6, the CDC said the variant made up more than half of all cases in the country.
What are key mutations? The delta variant has several important mutations in the spike protein, including T19R, del157/158, L452R, T478K, D614G, P681R, D950N mutations, according to outbreak.info. Two of these mutations — L452R and D614G — allow the variant to attach more firmly to ACE2 receptors, Live Science previously reported. Others, such as P681R, may allow delta to evade host immunity.
Why is the variant concerning? The delta variant is thought to be the most transmissible version of the novel coronavirus to date — potentially up to 60% more transmissible than the alpha variant and perhaps twice as transmissible as the original strain of coronavirus that emerged in Wuhan, China. In addition, some evidence suggests the variant can more easily evade existing vaccines than earlier variants of the coronavirus.
Do vaccines work? All the vaccines approved in the U.S. likely work against the delta variant, although exactly how well still isn't clear. For instance, Public Health England found the Pfizer vaccine was 88% effective against the delta variant, while health officials in Israel announced the Pfizer vaccine was only 64% effective against delta, The New York Times reported. However, Israel didn't control for differences in people who did and did not get vaccinated, making its data hard to interpret, according to The New York Times. The Pfizer vaccine remained strongly protective against severe disease and hospitalization. In a statement, Moderna said its vaccine neutralized the delta variant, and though it has not yet provided real-world data on infection, it is likely to work similarly to the Pfizer mRNA vaccine. Johnson & Johnson said their vaccine produced a strong neutralizing antibody response against the delta variant, but did not report on how much it reduces the odds of symptomatic disease, Live Science previously reported.
Variants of interest
Eta variant (B.1.525)
What is the variant? The eta variant, also known as B.1.525, was identified in the United Kingdom and Nigeria in December 2020, according to the CDC. It was labeled as a variant of interest on March 17, 2021, the WHO says.
Where is it? As of July 9, eta has been reported in 68 countries worldwide, according to GISAID.
What are key mutations? Eta carries some of the same mutations seen in the alpha (B.1.1.7) lineage, including E484K, which helps the virus evade certain antibodies, and the so-called H69–V70 deletion, which changes the spike protein's shape and may also help the variant avoid antibodies, according to The New York Times. It also carries a mutation called Q677H, which alters the 677th amino acid of the spike protein. The location of the swap hints that the mutation may help the variant enter cells more easily; but as of yet, it's still unclear whether eta is more transmissible than earlier versions of the virus. Other mutations in the variant's spike protein include A67V, 144del, D614G and F888L, per the CDC.
Why is the variant concerning? Due to the mutations present in eta, it's possible that monoclonal antibody treatments, convalescent plasma and antibodies from vaccinated people may not neutralize the variant as effectively as they neutralize earlier versions of the virus, according to the CDC.
Do vaccines work? Moderna's COVID-19 vaccine produces neutralizing antibodies that target the eta variant, although their neutralizing effect is slightly less robust "relative to those against the ancestral strain," the company announced on June 29.
Iota variant (B.1.526)
What is the variant? The iota variant, also called B.1.526, was first detected in November 2020 in New York City and was designated a variant of interest on March 24, 2021.
Where is it? The iota variant has been detected in at least 43 countries and all U.S. states. In the U.S., this variant accounts for 6% of all the SARS-CoV-2 samples sequenced since the variant was identified, according to Stanford University's dashboard. Worldwide, iota accounts for 2% of the coronavirus sequences.
What are key mutations? The variant has two notable spike-protein mutations: D614G and T951. The D614G mutation, which is found in several other SARS-CoV-2 variants, is thought to help the virus attach more firmly to the ACE2 receptors on human cells. The third notable mutation, called E484K, which is also on the virus's spike protein, is concerning because it seems to help the variant evade the immune system's antibodies.
Why is the variant concerning? Preliminary research, detailed in a May 16 CDC report, suggests the iota variant doesn't cause more severe COVID-19 and that it isn't linked to an increased risk for infection after a person is vaccinated, or for reinfection. However, the types of mutations found suggest the potential for the virus to be more transmissible and to evade some parts of the immune system.
Do vaccines work? Research published March 24, 2021, in the preprint journal bioRxiv (meaning it hasn't been reviewed by scientist peers yet) suggests the mRNA vaccines by Moderna and Pfizer, respectively, are protective against the iota variant.
Kappa variant (B.1.617.1)
What is the variant? The kappa variant, also called B.1.617.1, was first detected in India in October 2020, and it was designated as a variant of interest on April 4.
Where is it? The variant has been detected in at least 52 countries and 31 U.S. states, according to a Stanford University dashboard. As of June 24, kappa accounted for less than 0.5% of all sequences of SARS-CoV-2 analyzed since kappa emerged.
What are key mutations? Kappa has seven to eight mutations on the spike protein, according to a May 12 report by the CDC. Two of those mutations, called L452R E484Q, are on the protein's receptor-binding domain. These two mutations help the virus latch on more tightly to the ACE2 receptors on human cells. Another spike-protein mutation — D614G — is thought to make the virus more transmissible, while the so-called P681R mutation on the spike protein could be responsible for the variant's resistance to antibodies, researchers reported June 17 in the preprint journal bioRxiv.
Why is the variant concerning? This strain is potentially more transmissible and slightly less susceptible to mRNA vaccines compared with the original strain of the virus.
Do vaccines work? The mRNA COVID-19 vaccines (made by Moderna and Pfizer, respectively) are not as effective at neutralizing this variant, according to a correspondence published July 7 in The New England Journal of Medicine. How that translates to vaccine efficacy against mild, moderate or severe COVID-19 is still not clear.
Lambda variant (C.37)
What is the variant? The lambda variant, also known as C.37, was first detected in Peru in August 2020. On June 14, the World Health Organization (WHO) designated C.37 a global variant of interest, and dubbed it lambda.
Where is it? So far, lambda has been detected in 29 countries, with high levels of spread in South American countries. In recent months, the lambda variant was detected in 81% of COVID-19 cases in Peru that underwent genetic sequencing, and 31% of cases in Chile that underwent genetic testing.
What are key mutations? The variant has seven mutations in the virus's spike protein compared with the original strain of SARS-CoV-2 detected in Wuhan. Specifically, these mutations are known as G75V, T76I, del247/253, L452Q, F490S, D614G and T859N, according to the WHO.
Why is the variant concerning? Some of these mutations have the potential to increase transmissibility of the virus or to reduce the ability of certain antibodies to neutralize, or inactivate, the virus. For example, lambda has a mutation known as F490S located in the spike protein's receptor-binding domain (RBD), where the virus first docks onto human cells. A paper published in the July issue of the journal Genomics identified F490S as a likely "vaccine escape mutation" that could both make the virus more infectious and disrupt the ability of vaccine-generated antibodies to recognize the variant.
Do vaccines work? Right now, "there is currently no evidence that this variant causes more severe disease or renders the vaccines currently deployed any less effective," according to Public Health England.
Originally published on Live Science.
