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What happened to the predicted surge of the XBB variant of COVID-19 in CT?

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The new Omicron subvariant, XBB 1.5, is dominating Connecticut’s COVID-19 case burden. According to the Centers for Disease Control and Prevention, XBB accounts for roughly 80 percent of all infections in the Northeast.

But in spite of XBB 1.5 overtaking other Omicron subvariants and spreading to 38 countries worldwide, Connecticut’s hospitalizations, cases and deaths are nowhere near where the state was last year during the first Omicron surge. And early data shows the peak might have already passed.

“It’s not that we’re not seeing cases, it’s just that we’re not seeing the strain on the healthcare system. We’re not seeing that severe disease,” said Dr. Asha Shah, director of infectious disease and the epidemiologist for Stamford Hospital.

Historically, new COVID-19 variants have caused waves of sickness and death. The shift from the first COVID-19 variant to Delta in the summer of 2021 slammed hospitals and schools nationwide. The emergence of Omicron saw a massive spike of cases and deaths as that variant overtook Delta at the end of 2021.

But early reports of extreme immune evasiveness, a new wave doesn’t appear to be happening. While COVID-19 has seen moderate week-over-week increases in all metrics since winter began, the number of cases, hospitalizations and deaths is far below the peak of January 2022.

“We haven’t had anyone here on a ventilator for COVID-19, I want to say, for over a year,” Shah said. “The patients that do come in with COVID-19, most of them don’t require critical care.”

XBB 1.5, informally known as Kraken, arose from a recombination of two different subvariant strains of Omicron. This probably occurred in New York’s autumnal “variant soup.” To put it simply, someone was infected with two different Omicron subvariants at the same time. When such a viral co-infection occurs there’s a chance that the strains will combine into a new strain.

Early research on the Kraken indicated that it was much more transmissible and antibody evasive than its other Omicron cousins, leading to concern among public health experts and scientists that it might cause a wave of severe COVID infections.

New analysis suggests that while Kraken can slip past antibodies better than previous subvariants, it isn’t able to evade well enough to escape neutralizing antibodies entirely. A systemic analysis of antibody neutralization studies from Johns Hopkins in pre-print found that convalescent plasma was still effective at neutralizing the virus.

“It’s a glass half full,” said Dr. John Sullivan, author of the study and physician researcher from the Johns Hopkins Bloomberg School of Public Health. “Against XBB, we have a 20-60 fold drop [in neutralization] but that drop is still above the neutralization threshold.”

Dr. Sullivan found that neutralization was slightly better in patients who had been vaccinated and boosted but there was no statistically significant difference between the bivalent booster and the ancestral booster. Plasma derived from people who had been boosted at all was better able to grab the virus at lower concentrations of antibody. This suggests that while boosting and vaccinating are important, the immune system is doing a lot of work on its own to tune itself to Kraken.

So while the antibody evasiveness means that the new variant is untreatable with monoclonal antibodies, most patients will produce the antibodies they need to handle it with vaccination or exposure. It’s also likely that immune memory to prior vaccination and exposure is contributing to the body’s ability to fight off XBB.

When the immune system is exposed to a bacteria, virus or vaccine, it makes antibodies. Antibodies are proteins that grab onto specific parts of the immune stimulant. The binding part of the antibody is sort of like a key, it only fits a very specific chemical lock on a virus or bacteria. 

During infection and vaccination, the body does not produce just one version of an antibody. Thousands of different antibodies are made, each targeting slightly different areas of the virus. Each of these antibodies are made by different families of clones of immune cells. Instead of “monoclonal” your response is “polyclonal,” you make many different clones. 

Monoclonal antibodies are made by isolating the immune cell making a high-affinity antibody and reproducing in cell culture at an industrial scale. “Monoclonal” literally means “one clone.” It guarantees consistency in the treatment. You always know that a monoclonal antibody will bind tightly to a specific target. Essentially, a monoclonal antibody is a very small slice of an overall immune response.

While each antibody in a polyclonal response might not have the same ability to attach to a virus, it also means that a virus has to evade thousands of different antibodies, rather than just one. Kraken has successfully gotten around the most widely produced antibodies, the monoclonals, but it hasn’t escaped everything the immune system can throw at it. It also hasn’t gotten around antiviral drugs.

“The virus changed until it was resistant to monoclonal antibodies, so having a diverse group of antibodies that are a mixture, binding other places, still works,” Sullivan said. “It’s better to have a team rather than relying on one player.”

Kraken could be construed as a warning to public health. While it isn’t causing a wave of infections, it reminds us that the more space we give the virus to replicate, infect and recombine, the more chances we give it to become dangerous.

“If you have globally at least 2 million infections a week, that in essence allows the virus to run that number of experiments to run a week. Experiments to out evolve what we throw at it,” said Rob Wallace, an epidemiologist and author of “Dead Epidemiologists: On the Origins of COVID-19.”

Wallace explained that taking this seriously means investing in basic preventative measures in our lives and in public policy, in public health. Wallace said that this could take the form of hiring public health workers to help get people boosted, investing in air filtration and accommodating people who get sick with paid time off.

Wallace worried that the Biden administration’s posture of winding down the pandemic emergency response too soon would make the situation worse.

“If you are trying to convince people to take the [booster] vaccine and at the same time declaring that the pandemic is over … you can’t then complain that people aren’t taking the vaccine,” Wallace said.

So, while Kraken doesn’t imply that most people need to do anything special, other than, perhaps, getting boosted and wearing masks the vulnerable it does reveal some of the risks of allowing a virus to spread unchecked.

For people with immune disorders, transplants or the elderly, the new strain means that you shouldn’t take chances if you suspect that you have COVID-19. Sullivan said people really shouldn’t hesitate to get antiviral drugs if they’re getting sick. 

“We have effective therapeutic tools,” Sullivan said. “They should ask their doctor about available options, and there are options.”

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