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Omicron sub-variants: new fitter Covid-19 viruses start generating their own waves


The numbers are undeniable: even with patchy reports, Covid-19 cases and hospitalizations are rising again in the United States.

Cases are trending up in most states and are up more than 50% from the previous week in Washington, Mississippi, Georgia, Maine, Hawaii, South Dakota, Nevada and Montana. In New York, more than a quarter of the state’s population is in a county with a “high” community level of Covid-19, where the US Centers for Disease Control and Prevention recommends indoor masking .

Average daily hospitalizations have increased by about 10% since last week, according to data collected by the US Department of Health and Human Services.

The culprit this time appears to be a derivative of Omicron’s BA.2 subvariant called BA.2.12.1, which was first reported by New York state health officials in April.

BA.2.12.1, which grows about 25% faster than its parent virus, BA.2, accounts for nearly 37% of all Covid-19 cases in the United States, according to new CDC estimates.

BA.2 caused around 62% of all Covid-19 cases last week, up from 70% the previous week.

BA.2.12.1 isn’t the only offshoot of Omicron scientists are watching.

After weeks of decline, South Africa has seen its Covid-19 cases rise sharply in the past two weeks. Test positivity and hospitalizations also arose as scientists observed two relatively new subvariants, BA.4 and BA.5, dominate transmission in this country. Together, they accounted for nearly 60% of all new Covid-19 cases at the end of April, according to South Africa’s National Institute of Communicable Diseases.

These new sub-variants of Omicron are spreading all over the world. BA.4 sequences have been reported in 15 countries and 10 US states, while BA.5 has been detected in 13 countries and five US states, according to the website, which is run by a coalition of research centers academics and is supported by funding from the National Institutes of Health.

Like BA.2.12.1, BA.4 and BA.5 have a growth advantage over BA.2.

A new pre-print study, published ahead of peer review, indicates why BA.4 and BA.5 are gaining traction: they can evade antibodies generated by previous infections caused by the first Omicron virus, BA.1, the variant responsible for the huge wave of infections that hit many countries in December and January. They can also evade antibodies in people who have been vaccinated and have had breakthrough BA.1 infections, although this has happened to a lesser extent than in people who have not been infected.

Researchers in South Africa tested the ability of antibodies in the blood to deactivate the BA.4 and BA.5 viruses in a laboratory. In people who were unvaccinated but recently recovered from BA.1 infection, they found a more than seven-fold decrease in the ability of their antibodies to neutralize BA.4 and BA.5 viruses. In people who had been vaccinated but had recently had a breakthrough infection caused by BA.1, the drops were smaller, about three times weaker.

For comparison, the World Health Organization uses an eight-fold decrease in neutralization as the threshold for loss of protection that requires updating seasonal flu vaccines.

The study results led the researchers to write that “BA.4 and BA.5 have the potential to drive a new wave of infection”, making Covid-19 vaccinations and boosters crucial to stopping the spread. next wave.

“Our conclusions are, first, that Omicron by itself is not a great vaccine, is it?” said Alex Sigal, a virologist at the Africa Health Research Institute who led the study. “Just because you’ve been infected doesn’t mean you have much protection against what’s to come.”

Dr. Eric Topol, founding cardiologist and director of the Scripps Research Translational Institute, praised the research, noting that this lab was also the first to characterize the first variant of Omicron: “They were top notch all paths through the pandemic.

He said overall the discovery was not good news. Even people who recovered from Covid-19 infection as recently as December or January can be re-infected with these new subvariants.

“This decline in immune evasion or immune evasion has been pronounced in unvaccinated people,” Topol said, pointing out that only about 1 in 3 people in South Africa have been vaccinated against Covid-19.

For those who are vaccinated, “these people are not as bad, but they also have to deal with BA.4 and BA.5 with a less robust neutralizing antibody response,” he said. “The BA.4 and BA.5 mutations are proving to be a challenge to our immune response.”

Only a few dozen sequences of these viruses have been reported in the United States and Canada. Researchers say it’s just too soon to know if BA.4 or BA.5 will take off in the United States.

It wouldn’t be surprising if they did, said Andy Pekosz, a virologist and professor of molecular microbiology and immunology at Johns Hopkins University.

“We have seen this time and time again. When a variant becomes dominant in another country, it eventually ends up here in the United States and spread globally,” Pekosz said.

In the meantime, Topol said, we have our own subline to manage: BA.2.12.1.

“It can simulate the problems of BA.4 and BA.5,” Topol said. “We don’t know yet because there is no study like this from the Sigal lab.”

The BA.4 and BA.5 and BA.2.12.1 viruses have mutations at location 452 of their genomes. This region codes for part of the virus’s receptor-binding domain – the part of the virus that attaches to a doorway on the outside of our cells. The Delta variant and a few others detected mutations there. Researchers believe the changes there help the virus bind more tightly to our cells and hide from the frontline immune defenders called antibodies that try to stop the virus from invading our cells.

“It can also improve transmission between our cells,” Sigal said.

BA.4 and BA.5 also have changes at location 486, which is a bit of a headache because previous viruses that changed at that location didn’t work well. They collapsed.

“So this guy handles it. So we don’t know what it does,” Sigal said. “I suspect it’s a heavy escape mutation,” meaning it helps the virus hide from our immune system.

Scientists have started working to try to better understand BA.2.12.1, which has been detected in 22 countries, although most of the sequences come from the United States.

Pekosz said he grew copies of BA.2.12.1 in his lab and recently sent samples of the virus to other research groups for study. He said scientists have just started talking about experiments they want to do to try to answer two key questions: how fast does it copy itself and how well does it evade our immunity? ?

Before the SARS-CoV-2 virus, scientists thought coronaviruses didn’t change much. Pekosz said looking back, we don’t know what we don’t know.

As long as the virus continues to find hosts to infect, it will continue to evolve.

“This virus showed that it mutated slowly, but when it started picking up good mutations, they just kept coming and coming and coming,” he said.


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