COVID levels are so high, they're approaching 2020's initial peak, as the WHO urges those at high risk to take any booster they can get their hands on

It’s yet another sign that while the official pandemic state may be over, the days of COVID are far from it.

Viral wastewater levels are not far behind all of the pandemic’s 2020 peaks except for one—the initial peak of March 2020, which they’ve already surpassed. And they lag just slightly levels seen during the deadly Delta peak of late 2021, according to Biobot Analytics, which monitors such data for the federal government.

A forecast issued this week by Jay Weiland, a leading COVID modeler, came to the same conclusions. On Thursday, Weiland estimated that 650,000 Americans are becoming infected daily, with 1 in 51 Americans currently infected with COVID. 

Take note: JP’s model based on US wastewater indicates the current wave for infections is approaching the level of the ancestral, Alpha and Delta waves https://t.co/a53Pxbha6q

— Eric Topol (@EricTopol) September 8, 2023

An additional 7% to 10% of the U.S. population will be infected over the next month and a half, Weiland predicted.

Forecast out to mid October:

Prediction is difficult at the moment with a lot of factors at play, so this is a range for now. Peaks are always hard to predict.

Lower model run peaks this week. FLip is growing, but not fast enough to peak later than late Sept. pic.twitter.com/6idiApRyyP

— JWeiland (@JPWeiland) September 11, 2023

Both Biobot data and Wieland’s modeling show U.S. cases beginning to recede. But they may not fall much more, if any, before the anticipated fall and winter surge.

WHO flags concerning trend

Infections aside, COVID hospitalizations and deaths are continuing to rise, according to the latest data available from the U.S. Centers for Disease Control and Prevention. Hospitalizations rose nearly 9% from Aug. 27 through Sept. 2, the most recent period for which the federal health agency made data available. And deaths rose nearly 5% from Sept. 3-9.

The World Health Organization continues to receive reports on concerning COVID trends, including a growing number of countries reporting an increase in infections, hospitalizations, and ICU admissions, Maria Van Kerkhove, technical lead for COVID-19 response, said at a Thursday news conference.

Vaccination, in addition to early diagnosis and access to care, can prevent severe disease and death, she said. WHO officials encouraged those at high risk for poor outcomes from the virus, like the elderly and immunocompromised, to obtain a booster ASAP—even if it’s not the latest XBB formula being rolled out in some parts of the world.

Vaccinating and boosting with any available version “remains vitally important to saving people’s lives now,” officials said.

U.S. approves updated XBB boosters

All Americans ages 6 months and older are eligible to receive an updated COVID booster tailored to the XBB Omicron strain, the CDC announced this week.

The agency’s Advisory Committee on Immunization Practices voted 13-1 Tuesday to approve updated jabs from Moderna, Pfizer, and Novavax for the vast majority of U.S. residents. Shortly thereafter, the federal health agency announced that it had accepted the committee’s recommendation, and that vaccines would be available later in the week.

The U.S. Food and Drug Administration has yet to approve Novavax’s updated formula. But the agency authorized such boosters from Moderna and Pfizer on Monday.

The CDC anticipates having adequate booster supply and shouldn’t need to prioritize certain groups—like the elderly or immunocompromised—for first doses, federal health officials said at the Tuesday committee meeting.

All eligible should get the new booster when possible, Dr. Georges Benjamin, executive director of the American Public Health Association, told Fortune on Tuesday.

“It is clear that the vaccine remains safe and effective at all ages,” he said. “People at high risk will especially benefit from the vaccine.”

In a statement provided to Fortune, the American Medical Association on Tuesday said it welcomed the committee’s recommendations, contending that the updated jabs would prevent about 400,000 hospitalizations and 40,000 deaths over the next couple of years.

“We continue to strongly urge everyone to stay up to date on their COVID-19, influenza, and RSV vaccines to protect themselves and their loved ones from severe complications, hospitalization, and death,” the organization said, adding that it expected an increase in infections this fall and winter.

New booster, dying strain

Last year’s updated Omicron boosters, released around Labor Day, were bivalent, tailored to both Omicron and the initial strain of COVID. This year’s boosters are monovalent, meaning they’re tailored to just one strain of the virus: XBB.1.5 “Kraken,” which dominated in the U.S. and elsewhere late last year into early this year.

The strain is now nearly extinct. XBB.1.5 was estimated to be responsible for just 2.2% of U.S. infections Friday, according to the latest variant data the CDC has made available.

While the newest jabs are tailored to a dying strain of Omicron, they’re still expected to protect against severe disease and death from currently circulating strains, the vast majority of which are members of the XBB viral family.

The formula for the new vaccines “is highly similar to the EG.5-related variants circulating now,” Dr. Stuart Ray, vice chair of medicine for data integrity and analytics at Johns Hopkins’ Department of Medicine, told Fortune on Tuesday.

Recently released preliminary data shows that refreshed boosters should also offer decent protection against new, highly mutated Omicron spawn “Pirola” BA.2.86. It’s not a member of the XBB family, and is instead thought to have evolved from so-called “stealth Omicron” BA.2.

The updated vaccine’s protection against Pirola won’t be as good as the protection it offers against EG.5 and other XBB variants, Ray said. Still, there is more to immunity than antibodies, produced by B cells in response to infection and vaccination. The other, oft-forgotten half of the immune system, T cells, provides protection against severe disease. While T cells can’t prevent infection like B cells can, they still help soften the blow—of a BA.2.86 infection, EG.5 infection, or otherwise.

Rising concern for troublesome ‘flip’ mutations

While the United States’ “variant soup” remained largely unchanged Friday, according to new data released by the CDC, experts continued to sound alarm bells about a rising proportion of variants that share the same concerning mutations.

Around 93% of U.S. COVID sequences over the past month contain the mutation F486P, Raj Rajnarayanan—assistant dean of research and associate professor at the New York Institute of Technology campus in Jonesboro, Ark., and a top COVID-variant tracker—told Fortune on Friday. The mutation, located on the spike protein, increases the virus’s ability to effectively infect by binding more tightly with human cells. Rajnarayanan refers to it as this season’s signature mutation.

About half of U.S. sequences in over the same period picked up the F456L mutation, also in the spike protein, he said. The mutation makes the virus better at evading immunity from vaccination and prior infection. All top U.S. lineages have this mutation, he added.

What’s more, top lineages are also beginning to pick up the spike mutation L455F, which proffers further ease of infecting cells, Rajnarayanan added. 

Variant trackers refer to the F456L and L455F mutations as “flip” mutations, for complex scientific reasons involving amino acid changes. The duo is becoming one of the most concerning trends of the season, experts say, with nearly 20% of wastewater samples tracked by Biobot containing such mutations.

Latest US genomics
While EG.5’s and FL.1.5.1 variants are still most common circulating cause of cases, the growth advantage and rise of the FLip variants (see @BiobotAnalytics graph at right) and HV.1 are notable https://t.co/jjl2AnOYb5 and H/T @siamosolocani pic.twitter.com/ZyxhvEUvn9

— Eric Topol (@EricTopol) September 15, 2023

Once again this fall and winter, no one variant may gain a major advantage over others, experts say. But variants with the “flip combo” likely to become dominant and pose this season’s largest issue.

What’s more, it’s likely that highly mutated variant “Pirola” BA.2.86 picks up “flip” at some point, Rajnarayanan said, making it more of an issue—and potentially granting it the ability to spread more effectively.