‘Just stupid stuff’: Logistics and lack of testing stymied finding the Omicron variant in the U.S.

aAfter South African scientists alerted the world last week to the new Omicron variant of SARS-CoV-2, researchers here in the US warned that the highly mutated strain was already circulating on American soil. It was only a matter of time before someone found it.

On Thursday, health officials reported the country’s second Omicron infection, of a Minnesota man who attended an anime conference in New York days before symptoms began. Notably, he did not travel internationally, unlike the first case – a Californian who had recently returned from South Africa – suggesting that local transmission had occurred. But the timing of the discovery many wonder, “Why did it take so long?”

According to details released by the Minnesota Department of Health, the man, who is a resident of Hennepin County, home to Minneapolis, the state’s most populous city, first developed symptoms on November 22. A polymerase chain reaction (PCR) test was conducted on November 24. News of Omicron broke on November 25th. Minnesota health officials didn’t confirm from sequence data that his infection was due to the Omicron variant until a week later, on the evening of December 1.


By contrast, UK public health agencies found the first cases of the new strain in that country less than 48 hours after South Africa sounded the alarm.

“Although we have increased sequencing in recent months, we still have a problem with sampling,” said Eric Topol, founder and director of the Scripps Research Translational Institute in La Jolla, California, which is part of SARS-CoV-2. Organized by the Centers for Disease Control and Prevention last year. The US is only testing a quarter of what it is in the UK, and there is no systematic approach to testing travelers and people with breakthrough infections. So something new and scary is unlikely to fall on the swab, let alone the sequencer.


This puts the United States at a major disadvantage, Topol said. “Everything goes back to the same topic since the beginning of this epidemic,” he said. “We don’t have unity in this country, we have a balkanization, well, everything.”

The Thanksgiving holiday may have contributed to the slowdown. But this is not the full story. While the United States has significantly boosted its overall SARS-CoV-2 sequencing effort over the past year, progress has been patchy. Urban centers close to large academic centers tend to be well covered, while rural areas are less covered. This means that public health departments in large parts of the country are still flying blind, even as they discover ways to prioritize suspicious Omicron samples.

“People are trying to make a concerted effort to triage as much as possible, but we haven’t done enough as a country to increase sequencing capacity since the start of the pandemic, and here we are, and that’s a problem again,” said Lynne Wormbrod, of the Johns Hopkins Center for Health and Security, who co-authored a report in earlier this year outlining what an effective national monitoring program should look like.

Even when the patient lives in a major city like the case of Minnesota, logistical challenges can slow the process down to a crawl. In this case, it typically takes four to seven days for positive samples to be packaged and shipped to a facility that can perform the sequencing, Doug Schultz, a spokesperson for the Minnesota Department of Health, told STAT. The sequence takes another four to five days. With all phases of testing, this means that the genome that comes out of the sequencer is usually from samples collected 10 to 14 days ago.

“We’ve built every speed possible for this process,” Schultz said. “There is a certain amount of time it takes to collect, package and transport the baked samples.”

Minnesota is not alone. The shattered nature of health care in the United States means that when someone is scanned for SARS-CoV-2 in a hospital or clinic, the majority of those samples go to one of the large private testing providers like LabCorp and Quest. Some subsets of those samples will then be set aside for sending to county or state public health laboratories, which either sequence their own, or send the samples to academic laboratories or other industry partners to decode the virus genomes inside.

“In an ideal world, we would have a much stronger health system that would be more integrated with our public health agencies so that we could do testing and sequencing within the same network,” Wormbrod said.

All this filling out forms and statements can take days to weeks. The sequence itself can be as fast as 24 to 48 hours. It’s the logistics of sample transportation around this real bottleneck.

“It’s really just dumb stuff,” said Amy Mathers, associate director of clinical microbiology at Virginia Health, whose lab team is sequencing positive coronavirus samples in Virginia. Currently, they receive up to 300 samples a week, delivered in once or twice-weekly shipments via courier from the state’s Public Health Laboratory in Richmond. And if the MoPH identifies some suspicious samples due to travel history or contact tracing data, they will push them to the front of the line.

“We are much more integrated into the health system than we were before the pandemic,” Mathers said. But the data they pull from the sequencer does not reflect infections in real time. It usually shows what was circulated in the state 10 to 14 days ago. At the moment they are running samples from mid-November.

“We have tried and are still pushing for a system where people can send us positive samples directly,” Mathers said. But the problem was that it was difficult to find a way to register them in the public health system. The models were too confusing for hospitals.”

Her team has yet to find any cases of the Omicron variant, either in their sequence database or in any new samples, including samples taken from travelers and rushed to the front of the line. Mathers said her lab sequences every sample that shows positive results in her area.

During the delta-summer wave of upsurge, the backlog stretched even further. And in the end, all that sequencing didn’t help, she said. In September, her team arranged more than 1,000 samples. Each of them had a delta variable. But now, it’s more important than ever to tidy up every last vial of the virus in the state. “With the emergence of these new variants, we have to do heavy sampling to capture the only latent Omicron,” she said. “So I know if someone came to Charlottesville with the Omicron, we would find him. But it’s not the same everywhere.”

At a news conference Tuesday, CDC Director Rochelle Walinsky said the United States is currently arranging about 80,000 samples per week, among public, academic and private health laboratories. But it is not clear what percentage represents the actual time windows of virus spread.

This is not readily available information, Kelly Wroblosky, director of infectious diseases for the Association of Public Health Laboratories, told STAT via email. She said there did not appear to be an urgent and coordinated push by all the players to speed things up. “Distribution of sequencing to all states and many local jurisdictions is beneficial in this way because it brings sequencing closer to patients,” she wrote.

Until the broader geographic sequence is available, there is another step scientists can take now. Because of the omicron’s unique constellation of mutations, it leaves a tell-tale pattern with some types of PCR assay. These assays look for snippets of the virus’ genome, including the S gene, which codes for its barbed protein. In some assays, Omicron’s S gene extract does not appear – a phenomenon called ‘gene S leakage’. If scientists see it, this is an indication that the virus is likely not of the delta circulating type, and could be an omicron. In fact, that’s how officials in California and Minnesota discovered their injuries.

In the individual’s case in California, after he tested positive at a city testing site (using a PCR test that did not capture the gene S leak), his travel history prompted officials to send the sample to the lab of Charles Chiu, a researcher at the University of California, San Francisco, where his team performed a research test. They reported the S. gene leak. Within a few hours, they saw the signal and ran the sample into a portable gene sequencer, which works faster than the large devices typically used for mass sequencing. He gave them confirmation later that night.

When they heard about the Omicron variant, Minnesota officials contacted one of their clinical lab partners in New Jersey, whose standard test is already looking for leaks of the S gene. They found a handful of samples with a suspicious pattern, and sent them to Minnesota for sequencing. The samples arrived Tuesday, and it took the state’s team less than 48 hours to complete genetic analysis and discover that one of them was the new variant.

On Thursday night, officials in Colorado confirmed an additional case of Omicron in a person who had recently returned from South Africa, and in New York, officials confirmed five cases, likely caused by local transmission. Scientists expect to learn more in the coming days and weeks. “We’re late to the Omicron party, but they’re going to start showing up quickly,” Topol said. But without improvements, these discoveries will provide a picture of the variable’s prevalence in the past – and an incomplete picture at the time – not where it is today.

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