Arguably the most successful version of the Omicron coronavirus variant to date has been BA.2 – but it hasn’t been resting on its laurels. BA.2 has been picking up mutations, sometimes shifting into sleeker and, incredibly, even faster versions of itself. Global variant trackers have found 21 viral offspring associated with BA.2. Most of these look like underachievers, with mutations of little consequence. But two of these offshoots – BA.2.12.1 and BA.2.12 – have been fueling a rise in Covid-19 cases and hospitalizations in central New York state. And one of them, BA.2.12.1, is outpacing BA.2 in other regions, too. New data from the US Centers for Disease Control and Prevention estimates that BA.2.12.1 caused 19% of new Covid-19 infections in the US last week, up from an estimated 11% of cases the week before and 7% the week before that. The speed at which BA.2.12.1 is outpacing BA.2 is roughly as fast as BA.2 outcompeted its cousin BA.1, according to Trevor Bedford, an epidemiologist and genomic scientist at the University of Washington’s School of Public Health. Though BA.2 is still very much around, it’s lost some ground. Last week, it caused an estimated 74% of Covid-19 cases, according to the CDC data, down from nearly 76% percent the week before. Together, BA.2 and BA.2.12.1 accounted for an estimated 93% of new Covid-19 cases in the US last week. “BA.2.12.1 has increased rapidly in proportion in the US compared to other BA.2 sublineages,” especially in the region that includes New York and New Jersey, CDC spokesperson Kristen Nordlund said in an email. New sublineages emerge Last week, the New York State Department of Health alerted residents to the new sublineages, warning that they were spreading about 25% faster than BA.2 and were causing Covid-19 cases and hospitalizations to increase, particularly in the central part of the state. It urged New Yorkers to “act swiftly” to consider wearing masks, to get booster vaccine doses, to get tested if they had symptoms and to seek treatment if infected. Officials are concerned about BA.2 offshoots because they have swapped pieces of their spike proteins at key locations called L452Q and S704L. Virologists have seen mutations at those positions before. The Delta variant had a switch at 452, and this helped the virus bind more tightly to ACE2 receptors on our cells. “And those mutations are allowing the virus to enter cells faster and also contributing to evading antibody responses that are generated from vaccination or infection,” said Andy Pekosz of the Johns Hopkins Bloomberg School of Public Health. “What we really just don’t know right now is how much those mutations are going to be contributing to increased spread or increased disease severity,” he said. “That’s something that’s going to take some time for us to figure out.” Pekosz says he and others are working on that right now. That cases are rising in New York is a bit worrisome, too. It means these viruses are good at getting past our immune defenses. “The vast majority of people in New York have either been vaccinated or infected or both. And so what we’re seeing is reinfections. We’re seeing this immune evasiveness,” said Dr. Daniel Griffin, a physician and researcher at Columbia University Medical Center. Two other Omicron subvariants, BA.4 and BA.5, have begun to circulate at low levels in other parts of the world, including South Africa, Botswana, Germany and Denmark. They also have mutations at 452, among others. “I think it’s interesting that we were moving into a different kind of regime for SARS-CoV-2 evolution, in that the virus is able to pick up mutations that are more transmissible, at least we’ve seen three times now with Omicron. So I think from a scientific point of view, that’s interesting,” said Shishi Luo, associate director of bioinformatics and infectious disease at Helix, a company that’s been tracking variants of the coronavirus. Will new sublineages affect public health? What that might mean for public health is still very much an open question. Luo says it’s too early to know how well the current Covid-19 vaccines defend against the subvariants, but she’s hopeful that because they are related to BA.2, protection against severe outcomes like hospitalization and death will hold up. She notes that experts haven’t seen new subvariants drive up Covid-19 hospitalizations in countries like South Africa. So she’s hopeful that even if cases start to rise here, hospitalizations will continue to stay low. If you were vaccinated or previously infected – if your immune system has seen and recognized some of the virus before – and you catch Covid again, your chances of going to the hospital are reduced by about 90%, Griffin says. If you test positive quickly enough and get treatment, like monoclonal antibodies or Paxlovid, that’s another 90% reduction in the likelihood you’ll wind up in the hospital. “If we do everything right from here on out, we should not see a lot of people end up in the hospital,” Griffin said. He points out that getting Covid is still not risk-free. He does occasionally see people who wound up with long Covid after being vaccinated and boosted. “It’s just a gamble. As long as people are getting infected, you keep having a chance of that despite vaccines,” Griffin said.