Vaccine makers are so worried about the chance new variants will escape the protection offered by immunization that they are already testing booster shots and tweaking their vaccine formulas to specifically target some of the more troubling variants.

And doctors around the world are warning that even more variants will arise as the virus continues to evolve inside the bodies of the tens of millions of people it is infecting.

The CDC has designated three levels of variants: variants of interest, which have the potential to be dangerous but haven't caused much disruption yet; variants of concern, which are more contagious, evade some treatments, cause more severe disease or get past diagnostic tests; and variants of high consequence, which significantly evade the effects of vaccines or treatments.

"Currently there are no SARS-CoV-2 variants that rise to the level of high consequence," CDC says.

Here's what's known about the variants of interest and variants of concern:

Variants of interest

In laboratory tests, all the CDC-designated variants of interest have been found to resist the immune attack in blood taken from people who have recovered from Covid-19, as well as from people who have been vaccinated.

B.1.526 - First seen in New York last November, B.1.526 has what's called a 484 mutation. To understand the variants, it's important first to understand the mutations that characterize them. The E484K mutation is a change in the part of the virus called the spike protein -- that's the knobby structure that sticks out from the surface of the virus. The change, in a region called the receptor binding domain, makes the virus attach more easily to the cells it infects and also makes the virus less recognizable to the immune system.

Tests show it can in theory resist the effects of Eli Lilly's combined monoclonal antibody treatment, although it's not clear if that translates into treatment failure, the CDC says. Regeneron's antibody cocktail treatment for Covid-19 seems to work against it. It has also been shown to resist the immune attack in blood taken from people who have recovered from Covid-19, as well as from people who have been vaccinated. It accounted for just under 9% of samples sequenced in the US as of April 10.

New CDC research published this week shows it's not associated with more severe infection or a greater risk of reinfection.

B.1.526.1 - Also first seen in New York, B.1.526.1 has a different pattern of mutations when compared to the original strain sequenced from China, including one called L452R that seems to help the virus infect cells more easily while at the same time making it harder for antibodies to attack.

B.1.617 - First seen in India in February, this one is sometimes misleadingly called a "double mutant" because it has both an L452R mutation and a 484 mutation -- although not quite the same 484 mutation seen in other worrying variants.

B.1.617.1, B.1.617.2 and B.1.617.3 - These were all first seen in India, and were circulating before B.1.617. They all have the same mutations as B.1.617, plus a few extras.

Although Indian officials have said these new variants are driving the spike in coronavirus cases that is currently overwhelming the country's hospitals, the director of India's National Center for Disease Control, Sujeet Singh, said this week the evidence is lacking. "We have not been able to establish the epidemiological and clinical correlation completely yet," Singh said Wednesday.

British health officials, however, upgraded B.1.617.2 to a variant of concern Friday because of its rapid spread there. "There is currently insufficient evidence to indicate that any of the variants recently detected in India cause more severe disease or render the vaccines currently deployed any less effective," Public Health England said in a statement.

Dr. Chris Whitty, chief medical officer for England, said during a Royal Society webcast Thursday that the B.1.617 variants probably fall in the middle in terms of danger between B.1.1.7, which seems almost fully susceptible to vaccines and treatments, and B.1.351, which has been documented to infect people who recovered from infection with earlier variants of coronavirus, and also to partly evade the protection offered by vaccines.

B.1.525 - First seen in the UK and Nigeria, this one carries the E484K mutation. It's been found in fewer than 1% of samples tested in the United States. That surveillance is incomplete. This week, CDC director Dr. Rochelle Walensky said the United States is now sequencing approximately 8% of the country's roughly 450,000 weekly Covid-19 cases.

P.2 - Circulating in Brazil since last year, this variant also carries the worrying E484K mutation and has not been found widely globally.

Variants of concern

CDC defines these as variants for which there is evidence they are more transmissible, cause more severe disease, fail to respond to treatment, evade immune response or fail to be diagnosed by standard tests.

B.1.1.7 - The B.1.1.7 variant first seen in the UK has been shown to be at least 50% more transmissible and some evidence suggests it may cause more severe disease, although at least one study found no evidence of this. It carries 23 mutations, including one called N501Y that increases transmission.

It accounted for 60% of all samples tested in the US as of April 10, according to CDC. The University of Washington's Institute for Health Metrics and Evaluation estimates it now accounts for virtually all new infections in 23 states.

It's fully susceptible to monoclonal antibody treatments and vaccines.

"We are confident that the vaccines that are least currently available in the UK work against that, for practical purposes," Whitty said.

A team in the Gulf state of Qatar tested the effectiveness of the Pfizer/BioNTech vaccine during a time when Qatar was seeing circulation of the B.1.351 variant first seen in South Africa and the B. 1.1.7 variant first seen in the UK.

"The estimated effectiveness of the vaccine against any documented infection with the B.1.1.7 variant was 89.5% at 14 or more days after the second dose. The effectiveness against any documented infection with the B.1.351 variant was 75%," the researchers wrote in a letter to the New England Journal of Medicine.

B.1.351 - First seen in South Africa, this variant has both the E484K mutation that is linked with immune escape and the N501Y mutation suspected of helping make other variants more contagious. It has been shown to be 50% more transmissible and evades Lilly's dual monoclonal antibody treatment but not others. Blood tests and real-life use both suggest it can infect people who have recovered from coronavirus and also people who have been vaccinated against Covid-19.

Vaccine makers trying to get out ahead of the new variants by developing booster shots have focused on B.1.351, as it's the variant scientists most fear could elude vaccine protection. Moderna said Wednesday that a booster shot of its vaccine revs up the immune response against B.1.351 and another variant, P.1.
The good news is it does not seem to cause more severe disease, as initially feared, said Dr. Salim Abdool Karim, Director of the Center for the AIDS Program of Research in South Africa.

"It turns out in South Africa the evidence we have now is that it is not more severe," he told the Royal Society briefing. It does, however, escape the human immune response to a significant degree. It spread rapidly across South Africa, Karim has reported, accounting for 11% of viruses sequenced in October and 87% of samples sequenced in December.

"If you were infected with the virus before, you are not fully protected this time," Karim said. "About one-half of the individuals who were exposed did get infected again."

P.1 - First seen in Brazil, it also has both the E484K and N501Y mutations, with more than 30 others. It has been demonstrated to evade the effects of Lilly's monoclonal antibody treatment but not one made by Regeneron. Blood tests show it might escape both natural and vaccine-elicited immune responses.

B.1.427 - First seen in California, this one has the L452R mutation. CDC says it's about 20% more transmissible and may partly resist the effects of Lilly's monoclonal antibody treatment. Blood tests suggest it might be able to re-infect people who have been vaccinated against Covid or who have recovered but that has not been demonstrated in real life yet.

B.1.429 -- Another so-called California variant, this one has the L452R mutation along with others and is similar to B.1.427 in other ways. It accounted for 4% of samples sequenced nationally as of April 10.

Last month a team at the University of California, San Francisco did in-depth sequencing of more than 2,000 samples from people who tested positive for coronavirus across California. They found the B.1.427/B.1.429 variants increased from no samples in September to half of all samples taken in January.

They seem to replicate better in the noses of infected people, something that could explain their faster spread, the UCSF team, led by Dr. Charles Chiu, reported in the journal Cell. But they are not as transmissible as the B.1.1.7 variant.