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Last Friday, just a day after South African scientists first announced Discovery of the Omicron variant, Europe reported its first case: The novel coronavirus variant was in Belgium. Before the weekend ended, cases were detected in Australia, the UK, Canada, Denmark, Germany, Israel, Italy and all other countries.

But in the United States, scientists continued to search.

“If we start to see a variant emerge in multiple countries around the world, my usually intuition is that it’s already here,” said genomic epidemiologist Taj Azarian of the University of Central Florida.

Wednesday, American officials announced That’s what scientists found – in a California patient who had recently returned from South Africa. Until then Canada Six cases have already been identified; England had found more than a dozen.

Additional cases were identified Thursday in Minnesota, Colorado and New York, with more cases almost certainly being hidden, the scientists said. Why wasn’t the variant detected sooner?

There are several potential explanations, including travel patterns and strict entry requirements that may have delayed the variant’s entry into the United States. But there are also blind spots and delays in the country’s genomic surveillance system. With many labs now conducting a targeted search for the variant, detection speed can increase rapidly.

Scaling

Since the beginning of the pandemic, scientists have been sequencing genetic material from virus samples, a process that allows them to detect new mutations and identify specific variants. When sequencing is done routinely and on a large scale, it also allows researchers and authorities to track how the virus develops and spreads.

In the United States, such extensive genomic surveillance got off to a very slow start. While the UK quickly leveraged the national health system to launch an intensive sequencing program, in the United States early sequencing efforts, based primarily on university laboratories, were more limited and tentative.

even after CDC started a ranking consortium In May 2020, sequencing efforts were hampered by a fragmented healthcare system, lack of funding and other challenges.

In January, the United States was listing fewer than 3,000 samples per week as cases rose. According to the CDC’s control panel, much less than 1 percent of reported cases. (Experts recommend sequencing at least 5 percent of cases.)

But in recent months, the situation has improved dramatically, thanks to a combination of new federal leadership, funding infusion There is growing concern about the emergence and spread of new variants, experts said.

“Genomic surveillance has really caught on in the US, and that’s very good,” said Dana Crawford, a genetic epidemiologist at Case Western Reserve University.

country sort now Director of the Centers for Disease Control and Prevention, Dr. About 80,000 virus samples per week, and 14 percent of all positive PCR tests conducted in laboratories, considered the gold standard for detecting the virus, Rochelle P. Walensky said. A White House briefing on Tuesday.

The problem is that the process takes time, especially when done in volume. CDC’s own ranking process usually takes about 10 days to complete after taking a sample.

“We have really good surveillance in terms of quantity,” said Trevor Bedford, an expert in viral evolution and surveillance at the Fred Hutchinson Cancer Research Center in Seattle. “But by its nature, it lags behind compared to your case reporting. That way, we’ll have a good look at what’s left from two weeks ago.”

Dr. This type of delay is not uncommon in countries with large numbers of samples to sequence, Bedford said.

In some states, the timeline is even longer. Ohio Department of Health notesThe process of “collection, testing, sorting and reporting of the sample” from start to finish may take a minimum of 3-4 weeks.

But scientists said now that they know what they’re looking for, they should be able to speed up the process by prioritizing the samples most likely to be Omicrons.

Luckily, Omicron produces a different genetic signal in PCR tests than the Delta variant that currently accounts for all coronavirus cases in the United States. (In short, mutations in the new variant’s spike gene mean that the Omicron samples tested negative for the gene, while testing positive for a different explainer gene.)

Many labs are now accelerating these samples, as well as samples from people who have recently returned from abroad, for sequencing.

Dr. “All agencies involved in genomic surveillance are prioritizing these recent travel-related cases,” Azarian said.

The California case could have been flagged so quickly. The patient returned from South Africa on 22 November and began to feel ill on 25 November. The person tested positive for the virus on Monday, after which scientists sequenced the virus and announced two days later that they had detected Omicron.

Dr. “The rapid turnaround of the US genomic surveillance system is another example of how well our system has gotten in the past few months,” Crawford said.

blind spots

As surveillance improves, there are gaps in the United States, including very large geographic differences, that could slow detection of more cases.

“Some states are lagging behind,” said Massimo Caputi, a molecular virologist at Florida Atlantic University School of Medicine.

For example, in the past 90 days, Vermont ranked and shared about 30 percent of virus cases, and Massachusetts ranked about 20 percent, according to GISAID, an international database of viral genomes. Six states, on the other hand – Kentucky, Pennsylvania, Ohio, South Carolina, Alabama and Oklahoma – listed and reported less than 3 percent of their cases, according to GISAID.

What’s more, scientists can only sequence samples from detected cases, and the United States has often struggled to conduct adequate testing.

Founder and director of the Scripps Research Translational Institute in La Jolla, California, Dr. “Testing is the weakest part of our pandemic response,” said Eric Topol. “It’s been there since day one.”

While testing, like genomic surveillance, has greatly improved since the early days of the pandemic, it is still highly unstable. And while rapid testing at home has many advantages, shifting some testing from the lab to the home can present new challenges for surveillance.

“With increasing rapid diagnostic testing at home, these cases will not be sequenced unless this is followed up like a PCR test,” said genomic epidemiologist Joseph Fauver of the University of Nebraska Medical Center. The problem is not insurmountable, he added, “maybe there’s a little blind spot there.”

There are other, more optimistic reasons why scientists failed to detect more cases, even if they remained theoretical.

“Perhaps infected patients have mild symptoms and therefore are not being tested and are not subject to genomic surveillance,” said Janet Robishaw, Associate Dean of Research at Florida Atlantic University School of Medicine.

(This it’s still too early to know The scientists highlight whether Omicron causes more or less severe disease than other variants. Even if cases are disproportionately mild, which is not yet clear, the variant may have so far mostly infected young or vaccinated people and may be less likely to develop serious illness.)

It is also possible that until recently there was not much community spread of the variant in the United States. When cases are mostly isolated and linked to overseas travel, they can fly under surveillance radar.

Dr. “If we’re looking for single unrelated cases, it looks like we’re looking for a needle in a haystack,” Azarian said.

Although it is not yet clear where Omicron originated, the first outbreaks were detected in South Africa, where the variant is now common.

Dr. There are fewer flights between South Africa and the United States than between that region and Europe, where other early cases of Omicron have been detected, Caputi said.

And until the beginning of NovemberHe noted that the US has banned international travelers from the European Union and South Africa. Even when authorities lifted the ban, travelers from these places were required to present both the vaccine and proof of a recent negative Covid test. These measures may have delayed the arrival of Omicron.

Dr. “Omicron spread is likely to be left behind in the US,” Caputi said in an email.

Either way, he added that he expects scientists to find more cases soon.