By David Axe

The two most highly evolved COVID subvariants yet are becoming dominant all over the world. The XBB subvariant in Asia and the closely related BQ.1 subvariant in Europe and the U.S. are both more contagious than previous forms of the SARS-CoV-2 virus and more immune-evasive. That is, they reduce the effectiveness of many of the leading vaccines—and totally thwart monoclonal antibody therapies, according to some studies.

Disaster isn’t inevitable. India and Singapore have both logged big increases in XBB infections. Neither country has logged a sustained increase in COVID deaths. “I think that the main lesson from both India and Singapore is, ‘Don't panic,’” said Paul Anantharajah Tambyah, president of the Asia Pacific Society of Clinical Microbiology and Infection in Singapore.

Singapore’s strategy is simple: vaccinate and boost almost everybody. India’s success against XBB is a bit more nuanced, however. It seems a combination of natural antibodies from past infection, a middling vaccination rate, and a healthy mix of different vaccine types all contributed to India’s winning battle against XBB.

“Singapore and India strike me as very different cases,” said Lawrence Gostin, a Georgetown University global health expert. And it remains to be seen whether other countries can duplicate one strategy or the other. But at least there’s an emergency handbook as BQ.1 and XBB spread and health agencies all over the world brace for fresh waves of cases.

BQ.1 has an advantage over other COVID subvariants thanks to three major mutations on its spike protein, the part of the SARS-CoV-2 virus that helps it grab onto and infect our cells. These mutations make BQ.1 more contagious than its cousins. XBB has seven new mutations along the spike.

These and other mutations also give BQ.1 and XBB their shared ability to evade antibody therapies. These therapies aren’t the only way to treat COVID, of course—there are antiviral drugs and treatments that don’t include doses of antibodies.

At least one study has also highlighted the subvariants’ apparent high level of “fusogenicity”—that is, how well they fuse to our own cells. The higher a virus’s fusogenicity, the higher its potential to cause serious disease.

But it’s the new subvariants’ extreme contagiousness that explains why they’ve outcompeted other forms of COVID to become dominant across much of the world. Once XBB or BQ.1 arrives in a particular country, it’s likely a spike in cases will follow. What’s arguably more important is whether a spike in cases also results in a spike in the worst outcomes. Especially deaths.

Singapore beat its XBB wave the simplest way possible. The tiny Asian city-state, population 5.5 million, has “among the best-vaccinated and boosted population globally,” said Peter Hotez, an expert in vaccine development at Baylor College. Ninety-two percent of the population is fully vaccinated with one of four approved vaccines: the two messenger-RNA jabs from Pfizer and Moderna as well as separate protein-based and inactivated-virus vaccines from Novavax and Sinovac, respectively.

For comparison, just 69 percent of Americans are “fully” vaccinated, most with two doses of mRNA. Even more impressive, a whopping eight out of 10 Singaporeans have gotten a booster shot, as well—compared to around three out of 10 Americans. There might be more vaccine-induced antibodies in Singapore than anywhere else.

Those antibodies have kept cases low, meaning there aren’t a lot of natural antibodies in the city-state’s population. But when XBB came knocking last month, the vaccine antibodies were enough.

Infections surged to a daily peak of 12,000 new cases. But by the time the case-rate dropped back down to 4,000 new infections a day last week—well on its way to the long-term average of 2,000 new infections a day—only around 50 people had died. The death rate for the month-long XBB surge in Singapore has been only twice as high as the long-term COVID death rate of around one a day.

All that is to say, XBB drove a sixfold increase in COVID cases, but only a twofold increase in deaths. Scientists call that difference a “decoupling.” Cases go up. Deaths don’t.

Decoupling is one of the most important trends as the COVID pandemic grinds toward its fourth year. Thanks to a wall of antibodies from vaccines and past infection, the global death rate has been slowly dropping even as new variants and subvariants drive back-to-back waves of infections.

The main worry, when BQ.1 and XBB first appeared, was a “recoupling” of cases and deaths. It didn’t happen in Singapore. And it hasn’t happened in India, either. But India’s experience “is less clear-cut,” Hotez said.

After first showing up in India in August, XBB now accounts for the majority of infections in the country. There was a one-day spike in COVID mortality on Tuesday, when authorities reported nearly 1,400 deaths. That’s up from an average of just 20 or 30 deaths a day since August.

That one-day increase appears to be a result of uneven reporting from regional health officials, which has been a consistent problem in India. After all, no major increase in cases accompanied the recent increase in deaths. And there were similar isolated mortality spikes in January, March, and April.

The data from India is messy. But it doesn’t point to a sustained surge in COVID despite XBB’s new dominance. The question is why. With just 68 percent of its 1.4 billion people fully vaccinated with one of eight authorized vaccines—a mix of adenovirus, inactivated-virus and protein vaccines but no mRNA—and only 15 percent boosted, India is somewhere in the middle of the global pack for vaccination.

It’s possible that Indians benefit from widespread natural immunity from the waves of Delta and Omicron infections—44 million cases, in all—that swept over the country between May 2021 and January this year. “Another possibility is that their vaccines hold up better in terms of durability,” Hotez explained.

Many richer countries have leaned heavily on the mRNA vaccines. Messenger-RNA technology has the benefit of speed and flexibility. It’s fairly simple to update an mRNA vaccine for some new variant by swapping one bit of RNA for another.

But studies have indicated that the best conventional vaccines retain effectiveness longer than the mRNA jabs do. And the more different conventional vaccines you toss into the overall mix, the better. “There is a theoretical benefit to having a combination of different vaccines,” Tambyah said.

Better yet, individuals could mix vaccines. Grabbing at random from India’s authorized vaccines, that could mean one jab of Covishield, one jab of Corbevax and, say, a Bharat booster. “Many experts feel that the level of immunity will be more robust if the body has been exposed to different vaccines,” Gostin said. “India is the best example of that and I would not be surprised if it was playing a role in protecting the population against new waves.”

That India and Singapore have weathered, or seem to be weathering, XBB doesn’t mean other countries will, too. It’s possible Singapore (with its nearly-universal vaccination) and India (with its wide array of vaccines) are the outliers.

But the countries at least show us it’s possible to beat even the worst forms of COVID so far. Pick a strategy. Either vaccinate nearly everyone, or try a diverse mix of the most durable vaccines. Ideally, do both.

Doing nothing, on the other hand, might give XBB or BQ.1 a chance to do what other major subvariants have failed to do—drive up deaths alongside cases.