Last Friday, just a day after South African scientists first announced the discovery of the Omicron variant, Europe reported its first case: a new variant of the coronavirus was in Belgium. Before the end of the weekend, cases of the disease were identified in Australia, the UK, Canada, Denmark, Germany, Israel, Italy and other countries.
But in the United States, scientists continued to search.
“If we start to see a variant emerge in many countries around the world, usually my intuition tells me it’s already here,” said Taj Azarian, a genomic epidemiologist at the University of Central Florida.
On Wednesday, US officials announced that scientists had found it – in a California patient who recently returned from South Africa. By that time, Canada had already identified six cases; Britain has found more than a dozen.
The United States identified a second case in Minnesota on Thursday, and others are almost certainly hiding, scientists say. So why haven’t we found them yet?
Several factors may be involved, including travel patterns and strict entry requirements, that may have delayed the option’s appearance in the United States. But experts believe blind spots and delays in the country’s genomic surveillance system could also be factors. As many laboratories are now conducting targeted search for a variant, the rate of detection can increase rapidly.
Since the beginning of the pandemic, scientists have sequenced genetic material from samples of the virus, allowing them to detect new mutations and identify specific variants. When performed regularly and on a large scale, sequencing also allows researchers and officials to monitor how the virus develops and spreads.
In the United States, this kind of widespread genomic surveillance began very slowly. While the UK quickly used its national health care system to launch an intensive sequencing program, the first sequencing attempts in the United States, based largely on university laboratories, were more limited and one-off.
Even after the CDC launched the sequencing consortium in May 2020, sequencing efforts have been stymied by a fragmented healthcare system, lack of funding, and other problems.
In January, with cases skyrocketing, the United States sequenced fewer than 3,000 samples per week, according to the CDC dashboard, far less than 1 percent of reported cases. (Experts recommend sequencing at least 5% of cases.)
But the situation has improved dramatically in recent months, thanks to a combination of new federal leadership, an infusion of funding and growing concerns about the emergence and proliferation of new options, experts say.
“Genomic surveillance has really caught up with the United States, which is very good,” said Dana Crawford, a genetic epidemiologist at Case Western Reserve University.
The country is now sequencing approximately 80,000 virus samples per week and 14 percent of all PCR test positives, Centers for Disease Control and Prevention Director Dr. Rochelle P. Walenski said in a White House briefing on Tuesday.
The problem is that the process takes time, especially if it is carried out on a large scale. CDC’s own sequencing process usually takes about 10 days after receiving the sample.
“In terms of quantity, we have really good surveillance,” said Trevor Bedford, a viral evolution and surveillance expert at the Fred Hutchinson Cancer Research Center in Seattle. He added: “But by nature it lags behind your medical history. So, we will closely follow the events of two weeks ago. “
Such a delay is not uncommon in countries where large numbers of samples need to be sequenced, Bedford said.
In some states, the time frame is even longer. The Ohio Department of Health notes that from start to finish, the process “collecting a sample, testing it, sequencing it, and filing a report can take at least 3-4 weeks.”
But now that scientists know what they are looking for, they should be able to speed up the process by prioritizing samples that most likely belong to Omicron, scientists say.
December 2, 2021 12:20 PM ET
With any luck, Omicron generates a different genetic signal on PCR tests than the Delta variant, which currently accounts for virtually all coronavirus cases in the United States. (In short, mutations in the new variant’s thorn gene mean that Omicron samples test negative for that gene, while positive for another control gene.)
Many laboratories are now sending these samples, as well as samples from people who have recently returned from overseas, for sequencing.
“All genomic surveillance agencies prioritize recent travel-related cases,” said Dr. Azaryan.
Perhaps this is why the California case was noticed so quickly. The patient returned from South Africa on November 22 and began to feel unwell on November 25. The man was tested positive for the virus on Monday, and the scientists then sequenced the virus, announcing that they had found Omicron two days later.
“The rapid rollback of the US genomic surveillance system is another example of how much better our system has become over the past few months,” said Dr. Crawford.
While surveillance has improved, there are still gaps that could slow the detection of more cases in the United States, including huge geographic differences.
“Some states are lagging behind,” said Massimo Caputi, a molecular virologist at the Florida Atlantic University School of Medicine.
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For example, over the past 90 days, Vermont has sequenced and disseminated more than 30 percent of virus infections, and Massachusetts has sequenced more than 20 percent, according to GISAID, the international viral genome database. On the other hand, six states – Kentucky, Pennsylvania, Ohio, South Carolina and Alabama – each sequenced and reported less than 3 percent of their cases, according to GISAID.
What’s more, scientists can only analyze samples from identified cases, and the United States has often struggled to conduct a fair amount of tests.
“Testing is the weakest part of our response to the pandemic,” said Dr. Eric Topol, founder and director of the Scripps Translational Research Institute in La Jolla, California. “It was from day one.”
While testing, like genomic surveillance, has improved significantly since the early days of the pandemic, it is still very uneven. While there are many benefits to taking home tests quickly, moving some tests from the laboratory to the home can create new challenges for oversight.
“With the increase in home-based rapid diagnostic tests, if it is not followed by a PCR test, for example, these cases will not be sequenced,” said Joseph Fover, a genomic epidemiologist at the University of Nebraska Medical Center. “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 found more cases, although they remain theoretical.
“It is possible that infected patients have mild symptoms and therefore are not being tested and not subject to genomic surveillance,” said Janet Robishaw, senior associate dean for research at Florida Atlantic University College of Medicine.
(Scientists emphasize that it is too early to tell whether Omicron causes more or less serious illness than other options.young or vaccinated people who are less likely to get serious illness.)
It is also possible that the United States does not yet have a widespread prevalence of this variant among the population. If the cases are mostly isolated and related to overseas travel, they may be hidden under surveillance.
“We are kind of looking for a needle in a haystack if we are looking only for isolated cases that are not related,” said Dr. Azaryan.
While it is not yet clear where Omicron originated, the first outbreaks were detected in South Africa, where the variant is now widespread.
There are fewer flights between South Africa and the United States than between the region and Europe, where other early cases of Omicron have been detected, Dr.Kaputi said.
He noted that until early November, the United States banned international travelers from entering the European Union and South Africa. Even when officials lifted the ban, travelers from these locations still had to provide evidence of both vaccinations and a recent negative Covid test. These measures could delay the arrival of Omicron.
“It is possible that the spread of Omicron in the US is lagging behind,” Dr. Caputi said in an email.
In any case, he added, he expected scientists to find more cases soon.