Sequencing Used to Identify Delta, Other Coronavirus Variants

SciCheck Digest

Researchers use genomic sequencing — not the clinical tests used to diagnose patients with COVID-19 — to identify and track specific variants of the novel coronavirus, SARS-CoV-2, including the highly contagious delta variant. But viral posts try to deny the existence of the variant by misleadingly claiming there is “no ‘Delta Variant’ test.”

Tests that detect current infections with SARS-CoV-2, the virus that causes COVID-19, are known as viral tests. There are two types: a Nucleic Acid Amplification Test, or NAAT, and an antigen test.

Many of the NAATs use a molecular biology technique known as the polymerase chain reaction, or PCR, to detect even a very tiny amount of the virus in a specimen.

The PCR test takes advantage of some natural features of biology to essentially scan through all of the RNA present in a sample — such as a nasal swab — and search for the presence of coronavirus RNA.

The Centers for Disease Control and Prevention says NAATs “are unlikely to return a false-negative result of SARS-CoV-2,” and it recommends only laboratory-based NAATS, the most sensitive tests, to confirm infection. It also says saliva tests aren’t as optimal as those using swabs of the nose or nasopharynx (upper throat behind the nose).

An antigen test is designed to detect the coronavirus antigen, a structure on the surface of the virus that triggers an immune response. Also conducted via a nasal or throat swab, antigen tests are less sensitive than NAATs but inexpensive and can usually produce results in about 15 minutes. Getting a result from a NAAT test can take about an hour or even a few days.

Testing can help stop the spread of the coronavirus from those who test positive, because they can then isolate themselves from others. But, as we’ve explained, testing has its limitations. It can take a few days or even longer after exposure to the virus before it’s detectable by the diagnostic tests. So even some with negative results could be infectious.

Still, to help limit the spread, the U.S. has instituted travel requirements and recommendations. All international airline passengers, including U.S. citizens and residents, and those who are fully vaccinated, arriving in the U.S. must show “a negative COVID-19 test, taken within three (3) calendar days of departure, or proof of recovery from the virus within the last 90 days,” as the State Department explains.

The CDC also recommends that everyone, including the fully vaccinated, get a viral test three to five days after returning from international travel.

The CDC recommends that those who aren’t fully vaccinated avoid international travel, and if they must travel, to get a test one to three days beforehand. The unvaccinated also should self-quarantine for seven days after returning to the U.S., even if they tested negative before or upon returning.

International destinations may have their own testing requirements as well.

As for domestic travel, the fully vaccinated don’t need to get tested, but the CDC recommends the unvaccinated follow the same guidelines as those for international travel.

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The delta variant of the novel coronavirus — now the dominant version of the virus in the U.S. — has presented additional challenges as the country tries to mitigate the spread of COVID-19. The highly contagious variant is responsible for a surge in outbreaks across the country, particularly in areas with low vaccination rates. Vaccines still protect against the variant, especially against serious illness and death, but may be less effective against delta compared to other forms of the virus.

Yet false and misleading claims have recently sought to not only cast doubt on the seriousness of the variant, but question its existence.

One such meme shared on Facebook more than 12,000 times misleadingly asks, “Since there is no ‘Delta Variant’ test, how exactly are people being diagnosed with the ‘Delta Variant’?”

The same question was presented in a July 26 tweet shared by thousands that was posted by Errol Webber, a film producer and Republican who unsuccessfully ran for Congress in California last year. Similar posts have been shared hundreds of times each.

Adding to the misperception, at a White House press briefing July 30, Emerald Robinson, a reporter for the conservative outlet Newsmax, asked, of the delta variant, “How do you test, when — that it’s the dominant strain in the area, when people just test whether they’re COVID positive?”

White House Principal Deputy Press Secretary Karine Jean-Pierre, seemingly perplexed, said “we don’t test it” and that “we listen to public health and scientists, and they tell us that it’s the Delta variant.”

On Twitter, Robinson — who has nearly 400,000 followers — has since misleadingly claimed that “the Biden Administration is unable to provide any proof that Delta variant is real” and later that the administration “has no idea how to test for the Delta variant.”

But the various posts trying to cast doubt on the validity of the delta variant betray a lack of understanding of how variants are being identified and tracked. There is testing to identify delta and other variants, but it’s more sophisticated than the routine clinical testing — often by polymerase chain reaction, or PCR, tests — used to simply determine whether someone has COVID-19.

Dr. Benjamin Pinsky, an associate professor of pathology and medicine at Stanford University, told us in a phone interview that it’s worth first noting that “all the diagnostic tests are capable of detecting the delta variant — they just don’t distinguish it from different lineages.” In other words, the PCR tests do detect the delta variant as SARS-CoV-2.

Identifying and tracking specific variants, however, requires additional analysis.

A laboratory technician wearing protective equipment works on the genome sequencing of the SARS-CoV-2 virus and its variants at the Pasteur Institute in Paris on January 21, 2021. (Photo by CHRISTOPHE ARCHAMBAULT/AFP via Getty Images)

To do that, scientists use a process called genomic sequencing. As the Centers for Disease Control and Prevention explains, sequencing is a way to decode the genes of a virus to better understand factors such as its spread and evolution.

John Everett, who helps conducts such research at Penn Medicine to understand the virus’ presence in the Delaware Valley, explained it this way: “Research institutions, including Penn, study samples collected from the community by sequencing viral genomes in those samples. We identify mutations in the genomes, compared to the original Wuhan strain, where groupings of specific mutations are used to define viral variants or lineages.”

“We track the relative rise and fall of different lineages which we can break apart by zip code to build a picture of how the different lineages are spreading in our area,” Everett, the bioinformatics director for the University of Pennsylvania lab group behind the research, told us by email.

The group’s data show how the delta variant has rapidly become the main lineage identified in most samples tested from the University of Pennsylvania Health System.

Some findings done through PCR tests can provide insights into the suspected lineage present. For example, the alpha variant — first identified in the United Kingdom in September 2020 — caused PCR failures involving the virus’ S gene, which codes for the surface spike protein, because of the variant’s mutations.

The phenomenon of variants causing test issues is expected, Everett said, which is why PCR tests check against “multiple regions of the viral genome.” That’s “another reason why surveillance is important — to identify mutations in the community which may interfere with tests and adjust the tests as needed,” he said.

Dr. Marie-Louise Landry, director of the Clinical Virology Laboratory at Yale New Haven Hospital, noted that the S gene issue “was only suggestive of alpha” since it was only one of the characteristic mutations of alpha. Sequencing the whole genome, she told us by email, is still needed to confirm that it was indeed the alpha variant.

Pinsky, who is also medical director of the Clinical Virology Laboratory for Stanford Health Care, said his lab runs a second, different PCR test on samples that are positive for SARS-CoV-2 to look for specific mutations that are seen in variants of concern and variants of interest prior to sequencing.

For the delta variant, Pinsky said, what’s known as the L452R mutation is often a telling sign: About 94% of the samples analyzed by his lab that show that mutation are proven to be delta once sequenced, he said. Moreover, about 90% of all positive samples recently sequenced by his lab are delta, he said.

“Delta is certainly not a hoax,” Pinsky said.

And while some of the viral posts online suggest patients are being “diagnosed” with the delta variant, all the experts we consulted said that patients would not be typically informed of the lineage identified — though, in areas with predominantly delta transmission, patients may be able to make inferences.

Dr. Atul Butte noted to us in an email that sequencing analyses “are NOT clinical tests.”

“These sequences are used for public health tracking and epidemiology,” said Butte, a University of California, San Francisco pediatrics and epidemiology professor who also directs the university’s Bakar Computational Health Sciences Institute. “We wouldn’t deliver any different medical care right now, based on whether one variant is present or another.”

Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.

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Landry, Marie-Louise. Director, Clinical Virology Laboratory at Yale New Haven Hospital. Email to FactCheck.org. 3 Aug 2021.

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