Thursday 24 March 2022

Coronavirus variants: Facts about omicron, delta and other COVID-19 mutants


Multiple variants of SARS-CoV-2, the coronavirus causing the disease COVID-19, have

emerged across the globe. At the moment, two lineages of the omicron variant and the delta variant are the only variants with significant global circulation, with omicron accounting for the vast majority of recent COVID-19 cases, according to a report from the World Health Organization released March 15, 2022. Omicron, also called B.1.1.529, was first reported in November 2021 in Botswana and South Africa, and now accounts for over 99% of coronavirus genome sequences from recent COVID-19 cases in the global database GISAID, according to the WHO report.

Viruses mutate all the time, so these new variations have not been 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. In particular, a "variant of interest," according to WHO, is a variant that is increasing in prevalence in multiple areas and has mutations that are likely to affect viral characteristics, such as transmissibility or disease severity. Officials use the term "variant of concern," or VOC, once reliable data show that the variant has increased transmissibility — such as what's been seen with the omicron variant  — or other worrisome features, such as the ability to evade vaccines or cause more severe disease, as was the case with delta, Live Science previously reported

But the VOI or VOC labels can be removed if evidence shows that a variant no longer poses a major risk to public health compared with other variants, or they aren't circulating at significant levels, according to WHO. For example, the variants named eta, iota and kappa were once considered VOIs, but that label has since been removed and those variants are no longer being monitored, according to WHO. And in March 2022, WHO officials said that variants would be further designed as "currently circulating" or "previously circulating," according to the WHO report. As such, the alpha, beta and gamma variants were designated as "previously circling VOCs," and delta and omicron were designated as "currently circling VOCs." In addition, the VOIs named lambda and mu were designated as "previously circulating VOIs, according to WHO.

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


Where did the variant emerge? Omicron, formally known as B.1.1.529, is a highly mutated and highly contagious coronavirus variant first identified in South Africa. The WHO labeled omicron as a variant of concern on Nov. 26, 2021.

Where is it now? Omicron quickly spread around the world, causing a surge of COVID-19 cases in December 2021 and January 2022. As of mid-March 2022, omicron is the dominant coronavirus variant in the world, accounting for 99.9% of coronavirus genome sequences from recent COVID-19 cases in the global database GISAID, according to WHO.

At the beginning of December 2021, researchers spotted another version of omicron, and proposed splitting the omicron lineage into two sublineages: BA.1, the version initially found in Africa, and BA.2, for the newfound version. BA.1 was primarily responsible for the winter surge in COVID-19 cases, but cases of BA.2 have since increased dramatically in Europe and are beginning to rise in the U.S. and worldwide. Between March 6 and March 12, BA.2 accounted for an estimated 23.1% of new coronavirus cases in the country, Live Science previously reported.

What are key mutations? Omicron has more than 30 mutations in the genes that code for its spike protein, with 10 of those genes coding for parts of the "receptor binding domain," or the part of the spike protein that latches onto human cells, Live Science previously reported

Some of omicron's other mutations have also shown up in previous variants of concern. For example, omicron has the N501Y mutation, which is also found in the alpha variant, and is thought to make the virus more contagious, according to The New York Times.

Why is the variant concerning? The omicron variant has a very high number of mutations in the spike protein that appear to make it more transmissible and allow it to at least partially evade vaccines. Some studies estimate that omicron's BA.1 variant is 4 times more transmissible than the delta variant, according to CNBC. And BA.2 is more contagious still — it's estimated to be 1.5 times more transmissible than BA.1, CNBC reported.

Do vaccines work? Most COVID-19 vaccines, including those used in the U.S., prime the immune system against the spike protein, Live Science previously reported. Because of the high number of mutations that omicron has on its spike protein, scientists expected that vaccines would be less effective against omicron compared with previous variants. 

And indeed, there has been an increased number of breakthrough infections with omicron compared with earlier variants. A study published in March in The New England Journal of Medicine found that the vaccine effectiveness of two doses of the Pfizer vaccine was 65%, but this fell to about 9% more than 25 weeks after vaccination. However, with a booster shot, the vaccine effectiveness rose to 67%, and then fell to about 45% after about 10 weeks, the researchers found.

Vaccines also reduce the risk of developing severe disease or being hospitalized with omicron. A CDC report published in January found that a booster dose provided 90% protection against hospitalization with omicron. 


Where did the variant emerge? 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 now? Delta rapidly became the dominant variant in the U.S. and worldwide in the summer of 2021, but it would largely be replaced by omicron in mid-December 2021, according to Yale Medicine. Besides omicron, delta remains the only other VOC with a notable level of global circulation, according to WHO. By mid-March 2022, delta accounted for 0.1% of coronavirus genome sequences from recent COVID-19 cases in the global database GISAID. 

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 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 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.


Where did the variant emerge? The alpha variant, formerly called B.1.1.7, was first seen in the United Kingdom in September 2020, according to WHO(WHO). By December 2020, the variant had shown up in the United States.

Where is it now? Alpha is virtually extinct worldwide. After its emergence in the U.K., the alpha variant soon spread around the world, and became the dominant variant in the U.S. in the spring of 2021, according to The New York Times. But the delta variant replaced alpha as the dominant strain in the U.S. in the summer of 2021, the Times reported.  Cases of the alpha variant have since faded in the U.S. and worldwide. By March 2022, few to no genetic sequences from alpha had been reported worldwide, and the variant was designated a "previously circulating VOC," according to WHO. 

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 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).

Do vaccines work? Research to date suggests that the two mRNA COVID-19 vaccines (Pfizer and Moderna vaccines) are effective at preventing symptomatic infections with the alpha variant of the coronavirus. For instance, a study published June 28, 2021 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 reported in July, 2021.


Where did the variant emerge? The beta variant, formerly called B.1.351, was first detected in South Africa in October 2020 and was designated a variant of concern in December 2020, according to WHO.

Where is it now? Beta is also nearly extinct. It took off rapidly in South Africa in late 2020 and early 2021, and spread to over 30 countries, Live Science previously reported. But beta was never common in the U.S., and it was later replaced by delta in the places where it was once dominant, according to Nature News. Beta was also designated a "previously circulating VOC" in March 2022, according to WHO.. 

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 2021 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 2021 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 had 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.


Where did the variant emerge? 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 is no longer circulating widely. In July, 2021, gamma had been reported in 74 countries worldwide, according to the United Nations. But cases faded with the rise of delta and omicron, with few to no genetic sequences from gamma reported worldwide by March 2022, according to WHO. Gamma was also designated a "previously circulating VOC" in March 2022.

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 study, published May 12, 2021 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.

Variants of interest


Where did the variant emerge? The lambda variant, also known as C.37, was first detected in Peru in August 2020, according to WHO. On June 14, 2021, WHO designated C.37 a global variant of interest, and dubbed it lambda.

Where is it now? Lambda spread to a number of countries in the summer of 2021 and had high levels of spread in Peru and Chile, Live Science previously reported. But by March 2022, there was no circulation of the variant reported worldwide in the past 90 days, according to WHO.

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 2021 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? Data from the time when lambda was circulating did not show that the lambda variant caused more severe disease or reduced vaccine effectiveness, according to Public Health England.

MU VARIANT (B.1.621)

Where did the variant emerge? The mu variant, also known as B.1.621, was first detected in Colombia in January 2021, according to the WHO. On Aug. 30, WHO classified it as a "variant of interest," and named it mu.

Where is it now?  The mu variant caused some large outbreaks in South America and Europe in 2021, according to the WHO. But the mu variant did not out-compete the delta variant in terms of circulation, and by March 2022, there was no circulation of the variant reported worldwide in the past 90 days, according to WHO. 

What are key mutations?  Mu shares some concerning mutations with the beta variant, including mutations known as E484K and K417N, according to Medpage Today

Why is the variant concerning? The mu variant "has a constellation of mutations that indicate potential properties of immune escape," WHO officials said in August 2021. Early data in lab dishes show that antibodies generated in response to COVID-19 vaccination or previous infection are less able to "neutralize," or bind to and disable, the mu variant, the report said. However, this finding still needs to be confirmed by future studies.

Do vaccines work? According to Public Health England, there is "no real-world data on vaccine effectiveness" against mu. Studies in lab dishes have found a reduction in the ability of antibodies to neutralize the mu variant that is "at least as great as that seen with the beta variant,"  according to Public Health England. 

 Jeanna Bryner, Tia Ghose, Yasemin Saplakoglu and Nicoletta Lanese contributed to this article. 

Editor's note: This page was updated on March 23, 2022 to include the latest information on coronavirus variants.

Originally published on Live Science.  

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