What one variant's takeover means for the pandemic's future. Six weeks after it was first reported in South Africa on Nov. 24, the omicron variant of the coronavirus is sweeping away the previous delta variant. Does that mean that omicron will wipe out delta for good? Or will the two strains co-circulate forever? Increasingly, it looks like omicron's takeover from delta is assured — and that delta is unlikely to resurface in a meaningful way, even after omicron has burned through the population. In many states, omicron now makes up 99% or more of all coronavirus infections, according to an analysis by Trevor Bedford, a biostatistician and biologist at the Fred Hutchinson Cancer Research Center in Seattle. Bedford and his colleagues have been tracking genetic sequences collected from COVID-19 patients and have found that omicron infections began to outnumber delta infections in mid- to late December. Even in states with relatively less omicron, the variant is responsible for 80% or more of cases, Bedford wrote on Twitter on Jan. 5. When omicron first emerged, researchers worried that both variants might co-circulate. It was clear that omicron could spread like wildfire, but it wasn't clear whether this was due to an intrinsically better ability to spread, or whether omicron was just evading immunity in vaccinated and previously infected people, giving it targets that delta didn't have. As it turns out, however, omicron does evade immunity. But it's also intrinsically two to three times more transmissible than delta, and that explains omicron's world domination. "If you put them into direct competition, omicron is going to win, so in the population that is what is going to happen," said Dr. Shiv Pillai, a professor of medicine at Harvard Medical School who studies the immune system. "People will more likely get infected by omicron than delta, so delta will slowly fade away, and omicron will take over." Omicron is generally less severe than delta, thanks to a mix of pre-existing immunity in the population and omicron's preference for multiplying in the bronchi, or air passages, rather than the lungs. That means its takeover could ultimately lead to fewer deaths than if delta had continued its onslaught unhindered. And the huge wave of omicron infections may ultimately provide some protection against future variants and bring us closer to the end of the pandemic, one expert told Live Science. Still, the possibility of new variants is out there, and some form of the virus will be with us for the foreseeable future. Cross-immunity The spike protein of the omicron variant has dozens of changes in its proteins compared with the delta spike protein. This protein is the key the virus uses to get into cells; it's also the target of the antibodies generated by the COVID-19 vaccines. That means even if a person has been infected with a past variant or has been vaccinated, their immune system will not produce antibodies well-matched to omicron; their antibodies instead are primed to target the spike protein of the original variant of SARS-CoV-2 (which is more similar to delta than it is to omicron). However, there are still many amino acid shapes in common between the two spikes, Pillai told Live Science. Thus, researchers expect some level of cross-immunity between the two. A small study from South Africa, which has not yet been peer-reviewed, showed that this cross-reactivity does indeed exist. The study examined immune responses in vaccinated and unvaccinated people infected with omicron. The researchers, led by Alex Sigal of the Africa Health Research Institute in Durban, recruited eight unvaccinated and seven vaccinated participants with breakthrough infections. Three of the vaccinated patients had received two doses of Pfizer's vaccine, three had a single shot of J&J, and one had two shots of J&J. The researchers drew blood from the infected individuals approximately four days into their illnesses and then again two weeks later. They then exposed coronavirus in the lab to the blood samples, testing the body's first line of defense: neutralizing antibodies. These antibodies bind to the virus, preventing it from entering cells. Not surprisingly, compared with the blood taken initially, the blood from two weeks later showed a 14.4-fold increase in its ability to neutralize omicron in a lab culture of the virus. But neutralization of delta rose too, increasing by 4.4 times. That means an infection with omicron should boost protection against delta as well. This wasn't surprising, Pillai said. When exposed to the coronavirus, the immune system will create antibodies that recognize the shape of different portions of the spike protein. Some of these shapes are the same on both omicron and delta, so some anti-omicron antibodies will fight back against delta, too. This is the same mechanism by which a booster dose of the vaccine works, Pillai added. A recent study led by Alejandro Balazs, an immunologist at the Ragon Institute of Massachusetts General Hospital, MIT and Harvard, and posted on the preprint database MedRxiv found that while two doses of vaccine elicited no neutralization ability against omicron, a booster dose did fight the variant, and with a response only four to six times less strong than against the original coronavirus strain. This is remarkable, considering that a booster introduces the immune system to the original spike protein yet again. But this re-introduction boosts antibody levels very high, Pillai said. A fraction of these numerous antibodies are cross-reactive — they bind to the similarly shaped-bumps on both omicron and delta. A high enough concentration of antibodies against these shared shapes can still block infection, even if many of the vaccine-generated antibodies aren't shaped for omicron. "It's the antibodies to those common bumps which are protecting us when we get boosted," Pillai said. Transmission dynamics Omicron's apparent mildness compared with delta is one silver lining of its dominance. In any given person, catching omicron is likely less dangerous than catching delta (especially for the vaccinated). However, the absolute number of omicron breakthrough infections is higher than during the delta wave, meaning the next few weeks will be tough: The overall crush of people being infected all at once is still straining healthcare resources at the level of the delta wave or worse. According to Our World in Data, there were 119,661 patients hospitalized with COVID-19 in the U.S. as of Jan. 6, beating out the delta wave high of 97,811 and approaching last winter's peak of 133,268. But in the months to come, the omicron wave will also give many people new immunity to the coronavirus, including cross-reactive immunity that may protect them from the most serious outcomes if another variant does emerge. However, the South African study also highlights why so-called “natural immunity” from omicron on its own isn’t enough to protect people from reinfection or new variants. The study found stronger antibody responses to omicron infection in individuals who were previously vaccinated and more variable responses in people who were unvaccinated — in some, infection induced strong antibody responses, and in others, fairly weak ones. (That may be because the virus may activate proteins that turn off or block the optimal immune response – something vaccination doesn’t do.) Neutralizing antibodies from infection also wane with time, just as neutralizing antibodies from vaccination do. "The hard data will tell you that infection can protect you from infection to some extent, but when it comes to hospitalization and disease it's not proven as good," Pillai said. Ultimately, Pillai said, a combination of vaccines and omicron could help transition the world from a pandemic to endemic state, meaning that most people will have some pre-existing immunity to the coronavirus and spikes in infection will become less disastrous in terms of hospitalization, severe disease and death. Nevertheless, waning immunity will probably mean that some version of the coronavirus sticks around, and people may become vulnerable to serious outcomes as they get further from previous infection or booster shots. It's also possible that a more severe immune-evading variant could arise. In the future, Pillai said, antiviral drugs such as Pfizer's Paxlovid, which showed promise in clinical trials, will likely be key for reducing the damage caused by the continued circulation of SARS-CoV-2. Source
