Saturday, 30 January 2021

Coronavirus variant first seen in South Africa identified in South Carolina

Washington: The highly transmissible variant of the coronavirus first identified in South Africa has infected two people in South Carolina with no international travel history, state officials announced Thursday. These are the first cases in the United States involving the B. 1.351 variant, and the patients' lack of travel suggests that the variant is spreading in the community after an undetected introduction.

The B. 1.351 variant, first identified in South Africa in December and containing mutations that appear to enhance transmission, is considered by scientists to be more worrisome than the more widely publicized B.1.1.7 variant first seen in the United Kingdom. The latter is now present in more than two dozen U.S. states.

Three "variants of concern" are spreading across the planet, and they have been identified in the United States. A variant known to scientists as P. 1 has been spreading in Brazil and is linked to the disastrous new surge in cases in the Amazonian city of Manaus, where hospitals are once again overwhelmed. On Monday, Minnesota officials announced that they had detected the P. 1 variant in an infected person who had traveled to Brazil.

Scientists are not surprised by these developments. Public health experts had feared that the variants were already in the United States, undetected until now because of limited genomic surveillance of the virus. The Centers for Disease Control and Prevention, academic institutions and private companies are working to increase surveillance of the variants.

There is no evidence that the B. 1.351 variant is deadlier for the individual patient than more common variants. But if it's more transmissible, as scientists suspect based on preliminary data, the resulting boost to the infection rate would also increase hospitalizations and deaths.

"At this time, we have no evidence that infections by this variant cause more severe disease. Like the UK and Brazilian variants, preliminary data suggests this variant may spread more easily and quickly than other variants," the CDC said Thursday in a statement responding to the South Carolina cases.

The B. 1.351 variant contains a key mutation that appears to allow the virus to elude some of the onslaught of antibodies produced through vaccines or administered in drug therapies. At least one antibody therapy will not work against the new variants, and scientists are scrambling to create a new antibody that can block the new mutation.

Laboratory studies in recent days have found the mutation in the variant diminishes the ability of vaccine-induced antibodies to neutralize the virus. Whether that decreases vaccine effectiveness remains to be seen, but vaccine makers are working on new vaccines and booster shots that could be used if inoculations fail. The vaccines, scientists believe, will still work as planned in the short term.

The variants are different but share a few concerning mutations. Most prominent among them is one called E484K, which affects the structure of a portion of the coronavirus spike protein that enables the virus to latch onto and enter cells. The spike protein is the target for many antibodies - lab-generated ones used as drugs and those conjured by the immune system in response to a vaccine or natural infection.

David Ho, a professor of microbiology and immunology at Columbia University, compared the E484K mutation to having a lock changed and trying to use the same key to open the door.

Imagine that there were jagged triangles at the top of the spike protein, he said, and that the antibody had a perfect fit to that jagged edge. With the mutation, the triangle tooth is modified significantly in its shape. Now, it's a square. Suddenly, the antibody loses its ability to grab on to the virus, and the virus can escape and do its damage.

The most important short-term step the public can take is to try to stop the spread of the virus, scientists and public health officials have said - a message reiterated Thursday by the CDC in its statement. Vaccinations are critical to suppression of the pandemic, but they are in short supply. In the meantime, people should adhere to nonpharmaceutical interventions such as social distancing and masks.

Companies that make vaccines and therapeutics are working to keep up with the mutations. The most immediate challenge involves the drugs called monoclonal antibodies. Because they deliver just one or two laboratory-brewed antibodies that latch onto the virus in specific areas, the wrong mutation may render them useless more easily than vaccines, which trigger a multifaceted immune response.

Many scientists believe based on preliminary evidence that the vaccines will still work in coming months, but companies that make the vaccines are preparing to evolve their recipes as the virus mutates.

"What we see now is worrisome because there's a substantial decline in activity against the strain from South Africa, and that likely applies to the strain from Brazil because of similar mutations," Ho said. "It's absolutely wrong to say this is gloom and doom, but it's absolutely wrong to say it's absolutely rosy. I think the truth is in the middle, and we need to be sufficiently concerned that we should be preparing for the worst-case scenario."

This week, data released before publication from Ho's lab showed that pharmaceutical company Eli Lilly's monoclonal antibodies - one of which is authorized and one of which is experimental - would be eluded by the variant found on the mutant viruses first identified in South Africa and Brazil. Lilly chief executive David Ricks told investors and media members Tuesday that the company was working on developing an antibody that would neutralize those mutant versions of the virus.

The B. 1.351 variant "is capturing the most attention and interest because it has so many mutations and changes in the spike protein, and would be predicted to disrupt binding of most antibodies," Ricks said.

But in a sign of how fast the situation is evolving, he also said Tuesday that Lilly's current antibodies were "predicted to be effective against more than 99% of all strains that we see in the United States today." That was hours before it was disclosed that the Brazilian variant had been detected in Minnesota and two days before the South African variant was confirmed in South Carolina.

Scientists say the antibody cocktail made by Regeneron Pharmaceuticals probably will be effective against the variant. Although the variant probably will escape one part of its cocktail, the other component binds to an area that should not be affected by the current mutations, said Jason McLellan, a structural biologist at the University of Texas at Austin.

Christos Kyratsous, vice president of research at Regeneron, said the company was constantly monitoring for new sequences and screening those against its library of antibodies to monitor when it becomes necessary to change or add on to the cocktail.

"Biologically, this is something I totally expected," Kyratsous said. "There was the expectation from the beginning . . . One reason we chose a cocktail [of antibodies] is to have an insurance policy, if one of the antibodies stops working or does not work as well. The cocktail will still work."

Moderna announced Monday that it was working to develop and begin human tests of a vaccine specific to the South African variant. The company will test a third booster shot of its current vaccine to see whether boosting immunity to the original virus could protect against the variant.

Many scientists are eagerly awaiting results from a trial being conducted by Johnson & Johnson that was partially conducted in South Africa, for the first hint beyond laboratory tests of how well a vaccine may protect in an area of the world where the variant is circulating.



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