Last Friday, just a day after South African scientists first announced the discovery of the Omicron variant, Europe reported its first case: the new variant of the coronavirus was in Belgium. By the end of the weekend, Australia, Britain, Canada, Denmark, Germany, Israel, Italy and other countries had all found cases.
But in the United States, scientists kept looking.
“If we start to see a variant appear in several countries around the world, my hunch is usually that it’s already there,” said Taj Azarian, a genomic epidemiologist at the University of Central Florida.
American officials announced on Wednesday that scientists had found it in a Californian patient who had recently returned from South Africa. By that time, Canada had already identified six cases; Britain had found more than a dozen.
The United States on Thursday identified two more cases, in Minnesota and Colorado, making it clear that more are almost certainly in hiding, scientists said. Why was the variant not detected earlier?
There are various potential explanations, including travel patterns and strict entry requirements that may have delayed the introduction of the variant in the United States. But there are also blind spots and delays in the country’s genomic surveillance system. With many labs now performing targeted search for the variant, the rate of detection could accelerate rapidly.
Since the start of the pandemic, scientists have sequenced genetic material from samples of the virus, a process that allows them to spot new mutations and identify specific variants. When done routinely and on a large scale, sequencing also allows researchers and officials to keep an eye on the evolution and spread of the virus.
In the United States, this kind of large-scale genomic surveillance has started very slowly. While Britain quickly harnessed its national health system to launch an intensive sequencing program, the early sequencing efforts in the United States, based mostly on university labs, were more limited and ad hoc.
Even after the CDC launched a sequencing consortium in May 2020, sequencing efforts have been hampered by a fragmented health system, lack of funding, and other challenges.
In January, as cases increased, the United States sequenced fewer than 3,000 samples per week, according to the CDC’s Dashboard, well under 1% of reported cases. (Experts recommend sequencing at least 5% of cases.)
But in recent months, the situation has improved dramatically, thanks to a combination of new federal leadership, an injection of funds and growing concern about the emergence and spread of new variants, the officials said. experts.
“Genomic surveillance has really caught up in the United States, and it’s very good,” said Dana Crawford, genetic epidemiologist at Case Western Reserve University.
The country currently sequences around 80,000 virus samples per week and 14% of all positive PCR tests, which are done in the lab and considered the gold standard for detecting the virus, Dr Rochelle P. Walensky, director of the Centers for Disease Control and Prevention, said Tuesday during a White House briefing.
The problem is, the process takes time, especially when done in bulk. The CDC sequencing process typically takes about 10 days after receiving a sample.
“We have very good surveillance in terms of quantity,” said Trevor Bedford, expert in viral evolution and surveillance at the Fred Hutchinson Cancer Research Center in Seattle. He added: “But by nature he’s late in relation to your case report. And so we’ll have good eyes on things from two weeks ago.
This type of delay is not uncommon in countries with a lot of samples to sequence, Dr Bedford said.
In some states, the delay is even longer. The Ohio Department of Health notes that, from start to finish, the process of “collecting the sample, testing it, sequencing and reporting it can take at least 3 to 4 weeks.”
But now that scientists know what they’re looking for, they should be able to speed up the process by prioritizing samples that appear most likely to be Omicron, the scientists said.
Hopefully Omicron generates a different genetic signal on PCR tests than the Delta variant, which currently accounts for essentially all coronavirus cases in the United States. (In short, mutations in the spike gene of the new variant mean that the Omicron samples are negative for the gene, while also being positive for a different telltale gene.)
Many laboratories are now shipping these samples, along with samples from people recently returned from overseas, for sequencing.
“All agencies involved in genomic surveillance are prioritizing recent cases associated with travel,” said Dr. Azarian.
Perhaps this is how the California case was brought to light so quickly. The patient returned from South Africa on November 22 and began to feel ill on November 25. The person tested positive for the virus on Monday and scientists then sequenced the virus, announcing that they had detected Omicron two days later.
“The rapid turnaround in the US genomic surveillance system is another example of how our system has improved in recent months,” said Dr Crawford.
Even though surveillance has improved, there are still gaps that could slow the detection of more cases in the United States, including huge geographic variations.
“Some states are lagging behind,” said Massimo Caputi, molecular virologist at Florida Atlantic University School of Medicine.
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In the past 90 days, for example, Vermont has sequenced and shared about 30 percent of its virus cases and Massachusetts has sequenced 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 – have each sequenced and reported less than 3% of their cases, according to GISAID.
Additionally, scientists can only sequence samples from detected cases, and the United States has often struggled to perform enough testing.
“Testing is the weakest part of our response to the pandemic,” said Dr. Eric Topol, founder and director of the Scripps Research Translational Institute in La Jolla, California. “It’s been from day one.
Although testing, like genomic monitoring, has improved dramatically since the early days of the pandemic, it remains very spotty. And while rapid home tests have many advantages, moving some tests from the lab to the home can present new challenges for surveillance.
“With the increase in rapid diagnostic tests at home, if this is not followed up, for example, by a PCR test, these cases will not be sequenced,” said Joseph Fauver, genomic epidemiologist at the medical center of the ‘University of Nebraska. The problem is not insurmountable, he added, but “there may be a small blind spot here.”
There are other, more optimistic reasons why scientists have not detected more cases, although they remain theoretical.
“Maybe infected patients have mild symptoms and therefore are not tested and undergoing genomic surveillance,” said Janet Robishaw, senior associate dean for research at Florida Atlantic University College of Medicine.
(It is still far too early to know whether Omicron causes more or less severe disease than other variants, scientists point out. Even though the cases are disproportionately mild, which is not yet clear, it could be due to the fact that the variant has mainly infected people who are young or vaccinated so far, who are less likely to develop serious illness.)
It is also possible that there is not yet much community broadcast of the variant in the United States. While the cases are mostly isolated and linked to overseas travel, they could go under the surveillance radar.
“We’re kind of looking for a needle in the haystack if we’re only looking for unrelated isolated cases,” Dr Azarian said.
Although it is not yet clear where Omicron emerged, the first outbreaks were detected in South Africa, where the variant is now widespread.
There are fewer flights between southern Africa and the United States than between that region and Europe, where other early cases of Omicron have been detected, Dr Caputi said.
And until early November, the United States had banned international travelers from the European Union and South Africa, he noted. Even when authorities lifted the ban, travelers to these locations were still required to provide proof of vaccination and a recent negative Covid test. These measures may have delayed the arrival of Omicron.
“It is conceivable that the spread of Omicron is lagging behind in the United States,” Dr Caputi said in an email.
Either way, he added, he expected scientists to find more cases soon.