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On the surface, U.S. Covid-19 metrics continue to show improvement, with cases, hospitalizations, and deaths down dramatically from their peaks just two months ago. But some experts are growing increasingly nervous that the positive trends may be slowing down or even headed for reversal.

The country needs to prepare for another spike in cases, they’re warning, even if it turns out to be a minor one.

Europe has seen a surge of cases in recent weeks, and the situation there has typically foreshadowed that in the United States. Moreover, some U.S. wastewater surveillance sites are picking up increased viral levels. Individual testing is down, and is increasingly done at home, so it’s harder to see the full landscape.

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“We are breathing easier,” Ezekiel Emanuel, vice provost for global initiatives at the University of Pennsylvania and former member of the Biden transition team’s Covid-19 advisory board, told reporters Wednesday. “The mortality rate is coming down, the case rate is coming down, hospitalizations are coming down. But let’s remember, we’ve been here before.”

It’s not clear what will happen in the near future in the United States. Perhaps cases will continue to decline, if at a slower clip. There could be some resurgence, though a spike on the scale of the winter Omicron surge seems unlikely. Even if infections start increasing, political leaders at every level seem more willing to accept fluctuations in case numbers without reimposing mitigation strategies, particularly if hospitalizations and deaths do not rise sharply. Most people who are up to date with their Covid-19 shots remain strongly protected against severe outcomes.

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Below, STAT outlines some of the factors that are influencing case rates and parses some of what could happen next.

Fewer anti-Covid policies

While some cities and states rolled back anti-Covid efforts like mask requirements and capacity limits on businesses long ago, those who kept up their policies have let them lapse in recent weeks as the Omicron surge subsided. (One of the few remaining everyday mitigation policies is the mask mandate on planes and transit systems.) Similarly, many European countries have reverted back to few restrictions.

In the United States, with more than 30,000 cases still being reported a day, that meant there was plenty of virus out there even as masks increasingly came off. It’s a simple equation: Fewer protective measures, more lax behavior, and ongoing transmission can lead to more cases.

The variants

The term Omicron in fact refers to several related sublineages of the virus. The global explosion in cases late last year was first driven by one form, called BA.1. But it turns out that its sister virus, BA.2, is even more transmissible, and is gaining steam.

BA.2 has for weeks been dominant in places as varied as Denmark, South Africa, and India. Its growth has been slower in the United States, though it appears to be snowballing now. Federal data this week indicated BA.2 was accounting for some 1 in 4 infections, and experts think that it could have reached dominance in some states already, or will shortly.

The composition of which variants are causing infections can change — with a new entrant like BA.2 gaining in prevalence — even as overall infections come down. But BA.2 appears to be at least 30% more transmissible than other forms of Omicron, which could tilt the scales toward accelerating spread.

Notably, vaccines seem to stand up against BA.2 as well as they have against other forms of Omicron, and BA.2 seems to cause infections of the same average severity as its sister lineage. The main difference is its transmissibility.

Coming out of the initial Omicron wave, researchers hoped that all the infections caused by BA.1 would provide strong protection against BA.2. Indeed, the first studies have found that while reinfection with BA.2 was possible after a BA.1 case, it was rare. It’s not clear, however, how long the durability of that protection against infection will last.

Waning

There is a huge wall of immunity in most places in the world right now, from the combination of vaccination and past infections. But as people have learned through both the Delta and Omicron waves — when breakthrough infections and reinfections became more common — protection against infection can drop even as protection against severe disease and death is maintained.

It’s possible then that even more people are starting to see their protection against infection wane, particularly if their last shot or infection was months ago.

Studies have shown that the levels of antibodies — the immune system’s frontline fighters that can block the virus from establishing an infection — start declining within months, even after a booster shot. The U.S. booster campaign started last fall, so early takers may be becoming increasingly susceptible to an infection, particularly against a form of the virus as mutated as the Omicron family.

Notably, Pfizer and BioNTech this week asked the Food and Drug Administration to authorize another booster dose for people 65 and older, which could be tied to a fall vaccination campaign. It’s not clear if the FDA will authorize those shots or if they will be necessary, but they could top up older adults’ antibody levels ahead of the season when respiratory pathogens like the SARS-CoV-2 virus typically get a transmission boost.

So what does this all mean?

Experts worried about a potential increase in cases warn that the timing is ominous, with the government’s Covid-19 coffers dwindling and Congress seemingly not eager to authorize another round of funding for treatments, vaccines, and surveillance.

At the same time, case counts are increasingly difficult to interpret. Early on in the pandemic, a surge in cases would result in a spike in hospitalizations and deaths. But because so many people are now protected against severe outcomes, experts describe those metrics as “decoupled.”

The United States also has an array of treatments that can prevent at-risk people with Covid from getting so sick they need to be hospitalized (though some appear to not work as well against BA.2).

Still, if cases rise enough, some of those infections will lead to hospitalizations and deaths. Some European countries have started reporting upticks in hospitalizations on top of their surge in cases.

One worrying sign is that the United States has had a lower booster uptake than European countries. While many people are well-protected with the primary series of shots, boosters are more crucial to protect older people and people with underlying health conditions, particularly against Omicron. The lower booster rate in the United States explains why it saw a more damaging Omicron wave — with huge spikes in hospitalizations and deaths in addition to cases — than some European countries.

An increase in cases could also worsen the discord in the country over what steps everyone should have to take to protect others, as so many people are eager to leave the pandemic behind. Children under 5 remain ineligible for vaccines. And while healthy adults who are up to date with their vaccines don’t have much to worry about from Covid on an individual level, immunocompromised people — who mount less robust responses to vaccines —  fear what could happen to them if they contract the virus.

The changing landscape has led some experts to reassess their views on what could happen next. Nathan Grubaugh, an epidemiologist at Yale School of Public Health, said he used to think that protection from BA.1 infections and vaccination would keep a lid on cases even as BA.2’s prevalence grew.

But now, Grubaugh wrote in an email, “as time progresses and immunity to infection wanes, and we are also removing mask requirements, we may very well see a rise in cases associated with BA.2. In Connecticut, we estimate that BA.2 has crossed the 50% line and may completely sweep by mid April. The timing of this with masks coming off isn’t great, and I just hope that our leaders and us as a society are willing to put them back on if the cases do indeed start rising.”

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