If you’re anything like the majority of Americans — an estimated 60-plus-percent of them, according to government data — you’ve already had COVID-19.
And if you’re like most of those Americans, you had it fairly recently — during the enormous Omicron wave that engulfed the U.S. over the winter holidays.
The question now is whether you’re ready to get infected again — this time by a new subvariant that not only sidesteps some of your existing immunity but may also be more resistant to key treatments.
Two mutants matching that description, BA.4 and BA.5, are now taking off in the U.S. — and experts say they will soon outcompete the earlier versions of Omicron (BA.2 and BA.2.12.1) that have already been causing hundreds of thousands of new (and mostly unreported) infections every day for weeks on end.
“The next chapter of the pandemic ... is a story of immune escape,” Dr. Eric Topol, founder of the Scripps Translational Institute, recently predicted.
And experts say the U.S. is not doing enough to keep up.
Once upon a time, reinfection was rare; some scientists even suspected that natural immunity from a prior case of COVID would shield most people from ever getting infected again. Vaccination blocked more than 90% of infections as well.
But Delta cracked that immunity wall, and Omicron BA.1 breached it, propelling infection rates — including breakthrough infections — to record highs.
BA.4 and BA.5 then evolved to dodge the enormous amount of immunity induced by the original Omicron — and over the last month, their share of U.S. cases has been roughly doubling every seven days, signaling exponential growth. At the same time, U.S. reinfection rates appear to be rising. By July, BA.4 and BA.5 will likely be dominant nationwide.
The implications of Omicron’s faster-than-expected evolution — from a new variant that evades prior immunity to a rapid succession of subvariants that evade immunity acquired even from earlier versions of Omicron — are only just becoming clear.
The good news is that overall, COVID is less deadly now than ever before. Despite elevated case levels, there are now fewer U.S. COVID patients in intensive care units than at any previous point in the pandemic and the national death rate (about 300 per day) is as low as it’s ever been. Acquired immunity, multiple rounds of vaccination and improved treatment options are helping — a lot.
But there’s worrying news, too. The latest research suggests that advantageous mutations in the spike proteins of BA.4 and BA.5 could chip away at some of the progress we’ve made against serious illness. Among those preliminary findings:
Compared to BA.2, BA.2.12.1 is only modestly (1.8-fold) more resistant to antibodies from vaccinated and boosted individuals. But BA.4 and 5 are substantially (4.2-fold) more resistant — meaning more breakthrough infections, especially among people who previously had BA.1.
In turn, BA.4 and 5 are better at replicating in lung cells than BA.2 — a shift that could mean, according to one experimental model, more “pathogenic” as well (i.e., more likely to make you sick).
At the same time, BA.4 and 5 appear to be 20-fold more resistant than BA.2 to Evusheld — an important monoclonal antibody treatment that has been providing preemptive protection for immunocompromised individuals.
And finally, two recent preprint studies found that the coronavirus could continue to evolve in ways that would make it up to 80-fold more resistant to Paxlovid, the blockbuster antiviral pill that can currently reduce the risk of COVID hospitalization and death by nearly 90%.
Combined with waning vaccine protection and disappointing booster uptake among the elderly, the virus’s new trajectory — toward greater transmissibility, evasiveness and possibly pathogenicity — could affect vulnerable Americans in the months ahead.
Portugal, for instance, is currently experiencing a big BA.5 wave, and COVID deaths are again approaching winter’s Omicron highs, even though 87% of the Portuguese population has been fully vaccinated — 20 points higher than in the U.S. In contrast, the official COVID death count in South Africa remained fairly flat during that country’s recent BA.4 spike (though excess deaths were up sharply). In South Africa, just 5% of the population is over 65; in Portugal, that number is 23%. The U.S. — where seniors represent 16% of the population — is much more like Portugal demographically. Even small setbacks in protection for the immunocompromised and the elderly can have a real impact.
The same goes for a “new normal” that involves regular reinfection — which seems to be where the U.S. is heading. Dying isn’t the only downside of COVID. For one thing, long COVID is real — and the more times the virus infects you, the more opportunities it has to trigger lingering symptoms.
Then there are all of the usual drawbacks of getting sick: missing school, missing work, losing wages, juggling childcare, canceling events and spreading the virus to other, more vulnerable people. Each of these problems becomes much more problematic when it happens again and again on a massive scale — as opposed to the more modest and manageable scale of, say, the flu, which is far less contagious than COVID and only tends to reinfect us every few years.
Americans already recognize how disruptive and possibly dangerous regular reinfections would be. According to the latest Yahoo News/YouGov poll, a substantial majority (61%) say it would be a very (29%) or somewhat big problem (32%) "if, in the future, you become infected with coronavirus multiple times a year” — while just a quarter or so (27%) say it would be a not very big problem (17%) or not a problem at all (10%).
So far, few Americans — just 28% — think it’s likely they’ll be reinfected that often, and experts say it’s still possible to reduce the odds, which are now rising fast, to more closely match expectations. But they also say the U.S. is way behind the curve.
Last week, Moderna announced that its leading candidate for a fall booster shot is partly based on Omicron BA.1 (which is now extinct in the U.S.) rather than BA.4 and BA.5 (which represent 13% of cases and climbing). As the New York Times put it, the “worry that the virus is evolving so quickly that it is outpacing [our] ability to modify vaccines, at least as long as the United States relies on human clinical trials for results.” A faster method — likely based on data from laboratory tests and trials involving mice or other animals — may be necessary to ensure that boosters remain effective.
To minimize infections, next-generation vaccines may be necessary as well. As Dr. Deepta Bhattacharya, a professor of immunology at the University of Arizona, wrote Monday in the New York Times, “vaccines that are received up the nose or in the mouth position memory cells and antibodies near the sites of infection and offer potential ways to prevent symptoms and perhaps even infections altogether. Some of these types of vaccines are now in clinical trials and could become available soon.”
Meanwhile, Bhattacharya continued, “groups of researchers are also studying single vaccines that could work against all versions of the novel coronavirus. These vaccines, which aim to be variant-proof, make it difficult for the virus to outmatch the immune system. They have shown great promise in animal experiments. Some are entering clinical trials and could be available in the next few years.”
Improving ventilation would help as well. “If we are going to have waves every few months, we need to do something *sustainable* to reduce transmission,” COVID expert Prof. Christina Pagel recently tweeted, citing the “once-in-decades opportunity” that “now exists to make sustained improvements to public and private indoor air quality."
“It’s not only about masks — esp where they are impractical in restaurants/pubs/gyms,” Pagel, who is based in the U.K., added. “We have solutions!”
But the U.S. is not funding an Operation Warp Speed for next-generation vaccines or improvements in air quality. Instead, Republicans in Congress are blocking a modest $10 billion in new COVID spending, forcing the White House to cut money for testing so the U.S. is prepared to purchase the bare minimum this fall, such as existing pills and vaccines.
That combination of obstruction and lack of ambition represents what Topol and others have described as “COVID complacency.” Yet if the sudden rise of BA.4 and BA.5 tells us anything, it’s that COVID hasn’t become complacent with us.
New versions of the virus will never set the U.S. back to square one. But they will keep making our path out of the pandemic more disruptive and even dangerous than it has to be — unless we do more to keep up.