Should Americans be worried about COVID — again?

COVID-19 cases are dropping in the U.S. and mask mandates are being repealed all over. Yet over a third of the wastewater sample sites across the U.S. showed rising COVID-19 levels in the first 10 days of March. So is COVID-19 going away or not?

For the experts, there are quite a few reasons to believe Americans shouldn’t let their guard down just yet. “The world has decided COVID is over for some reason — and that really worries me,” said Akiko Iwasaki, a professor of immunobiology at Yale School of Medicine. “Lifting all of these mandates so quickly is asking for trouble.”

State of play

Throughout the pandemic, U.S. COVID-19 trends have largely trailed those in Europe and the U.K. by a few weeks. For most of the European region, COVID-19 cases are on the rise again after plunging from their winter omicron peaks.

“With cases rising abroad, scientific and medical experts have been clear that in the next couple of months, there could be increasing cases of COVID-19 here in the United States as well,” White House press secretary Jen Psaki warned during a briefing Tuesday night.

Her remarks came just two weeks after the White House dropped its mask requirements.

“What’s happening in Europe could very well be a preview for the U.S., especially without masks,” Yale’s Iwasaki said.

There are three main factors driving the uptick in international infections, all of which could apply to the U.S., experts said. The first is that omicron’s dubious cousin, labeled BA. 2, is reportedly more transmissible than its predecessor, according to a pre-print study from Denmark. In Europe, it has quickly overtaken the initial omicron strain, BA.1, and now accounts for the majority of cases in the U.K., according to its Office of National Statistics.

This hasn’t happened in the U.S. just yet, though over the past few weeks BA.2 has been rising in prevalence in the U.S. It currently accounts for just under a quarter of overall cases, according to the Nowcast data from the U.S. Centers for Disease Control and Prevention (CDC).

Data from the U.K. Health Security Agency show that the country’s rise in COVID-19 cases happened concurrently with BA.2 accounting for more than half of overall infections.

Andy Pekosz, a virologist at Johns Hopkins Bloomberg School of Public Health, said that it’s important to look at whether a variant’s rise in prevalence corresponds with an increase in cases overall. Though the percentage of BA.2 cases in the U.S. has nearly doubled in the last week, there hasn’t yet been a corresponding rise in COVID-19 infections, he pointed out.

A reason for the lag in rising U.S. COVID-19 cases rising could be “the delay in the appearance of BA.2 here,” Pekosz said. “The U.S. was also a few weeks behind most of Europe in lifting public health interventions — so the fact that BA.2 is growing here and public health interventions are being lifted will make it difficult to assess the contribution of each to any future increase in cases.”

Waning immunity is another factor driving the spike in infections abroad. Despite high vaccination rates across much of Europe, booster rates still hover around 50%. In the U.S., booster rates are even lower, according to the CDC. Protection from the initial two-dose vaccine series wanes after six months. Plus, immunity from prior infection also decreases over time and newer variants can render antibodies from past strains less effective.And the third factor is that mask mandates have lifted across the globe and people’s behavior has changed. This isn’t the sole cause of rising cases, but combined with waning immunity and a more transmissible variant, it certainly could contribute to a rise in cases.

“Irrespective of what variant is circulating, when those public health interventions go away, you should expect to see either a plateauing, or maybe a slight bump up in cases,” Pekosz said.

What are experts concerned about now?

BA.2 appears to be no more severe than omicron, meaning that for most healthy, vaccinated people, symptoms are pretty mild. British researchers found that BA.2 does not seem to carry a higher risk of hospitalization than the original omicron mutation.

But concerns lie in the many unknowns with omicron, which is still relatively new. The same U.K. researchers found cases of reinfection with BA.2 after omicron infection, meaning people can’t rely on prior immunity to prevent future infections. Studies are ongoing to better understand why that might be the case with BA.2.

Some epidemiologists have expressed concern that the virus may be evolving to produce more problematic variants. European researchers argue in Nature Reviews Microbiology that omicron demonstrated COVID-19’s ability to mutate rapidly over a short period of time in order to better evade a person’s immunity and even to diverge genetically among sub-lineages, as BA.2 does.

Pekosz said the question of whether omicron can cause long COVID is still largely a mystery. Even less is known about how BA.2 factors into the long COVID equation. The condition, in which symptoms of the virus linger long after infection, can be debilitating and has been linked to serious neurological and cardiac problems.

“It’s not clear how effectively omicron infection leads to long COVID,” he said. “Again, it’s so different from other variants, it wouldn’t surprise me if it had a different rate of inducing long COVID.”

What protective measures do we have?

Two years of pandemic life have given us some strategies for softening the virus’s blow.

There’s no indication, yet, of plans to bring masks back. Face coverings have been ditched in schools, and holdouts such as public transit are set to drop their requirements next month.

Ali Mokdad, a professor at the Institute of Health Metrics and Evaluation and chief strategy officer for population health at the University of Washington, said he does not think it’s necessary to bring back mask mandates in the U.S. right now — especially with warmer weather on the way. But in higher risk settings, and for more vulnerable populations, he recommends masking up.

Pekosz, from Johns Hopkins, said that should include kids under five who still have not been approved for the vaccine and other unvaccinated school-age children. Children under 17 were hospitalized at alarming rates during the omicron surge.

“If you’re in one of those groups that are at high risk of severe COVID, it’s perfectly acceptable for you to continue to mask up when you go inside or in group settings,” Pekosz said. “I’ve always encouraged people if they don’t feel comfortable not wearing a mask, they should put a mask on and continue to do that.”

Experts have continued to emphasize that the best protection we have against the virus — and against severe disease and long COVID — are vaccines. The two-shot messenger RNA vaccines and boosters, such as those made by Pfizer BioNTech and Moderna Inc., reduce the risk of severe disease. But most people are due for a booster, which is essential for bolstering immunity against newer variants.

According to several studies, two shots of the vaccine plus a booster dose were effective in preventing hospitalization with both delta and omicron, with an added bonus for those who have also had a breakthrough infection.

Antivirals and at-home tests are more widely available than during prior surges, which may help if COVID-19 cases start to rise sharply again. Funding for new treatments is strained though, the White House has warned. This month, the administration of U.S. President Joe Biden opened its second wave of at-home test ordering, allowing households that have already received their four tests to request another round through the U.S. Postal Service program.