The vaccines going in our arms could become less effective as the coronavirus mutates, a problem that demands scientists meticulously track variants to protect us.
The United States lags many other countries in employing the essential tool for keeping abreast of variants – gene sequencing – increasing the risk that a variant could spread undetected.
This year, the United States ranks 33rd in the world for its rate of sequencing, falling between Burkina Faso and Zimbabwe, according to COVID CoV Genomic, led by researchers at Harvard and MIT. The top three nations – Iceland, Australia and New Zealand – sequenced at a rate 55 to 95 times greater.
Sequencing happens behind the scenes when someone gets tested for the coronavirus. If the test is positive, the sample may be sent to another lab for sequencing, especially if the person has had COVID-19 before or has been vaccinated. That provides the genetic code of a virus, laying out for scientists a precise map for how to defeat it.
For arcane reasons, sequencing results in the U.S. go only to researchers, not to those who got tested. That could become a problem if the variant demands a different approach to treatment or proves resistant to existing vaccines.
Public laboratories in the United Kingdom, considered a model for tracking the virus, sequence a third of positive coronavirus tests, according to the COVID-19 Genomic UK Consortium. Through those efforts they discovered the B.1.1.7 variant first in September. On Dec. 14, scientists there reported this new variant was far more contagious and could be more lethal.
Until recently, only a minuscule fraction of samples in the U.S. were sequenced. Under the Biden administration, the Centers for Disease Control and Prevention is spending an additional $200 million on sequencing, quadrupling the rate of testing starting in mid-February.
The CDC tries to sequence at least 7,000 positive test samples a week, about 2% of new cases. Some say it needs to do more; a 2% rate could mean not catching new variants early enough.
“We’d really like to get that into double digits or more,” said Joel Sevinsky, founder of Theiagen Genomics, which helps public health officials track outbreaks.
By early January, laboratories in the U.S. had detected only 76 cases of the variant first detected in Britain. It was estimated at 5% of new cases. Since then, the variant has exploded. Last week, it made up an estimated 32% of new cases. Another fast-spreading variant, B.1.526 – which was first detected in New York – reached 36%, according to CoVariants.org.
Samuel Scarpino, director of the Emergent Epidemic Lab at Northeastern University in Boston, said he spends hours each day trying to track the U.K. variant but cannot say definitively how widespread it is in Massachusetts.
“And the reason I don't know that is because I've not found a representative publicly available data set, for example, that the CDC puts out on B.1.1.7,” he said. “There’s good evidence that what we’re doing now is not enough.”
The CDC has begun asking laboratories in each state to provide weekly samples, based on population, for it to analyze.
“Is it enough?” said Mark Pandori, director of the Nevada State Public Health Laboratory. “That’s a difficult question to answer; we don’t know.”
As more people get vaccinated, the rate of sequencing will increase if new coronavirus cases fall significantly. Last week, however, the number of U.S. cases rose, and some public health officials worry the U.K. variant could trigger another surge. They also are watching the New York variant, concerned that it may be resistant to vaccines.
In an emotional plea, CDC Director Rochelle Walensky urged all Americans to get vaccinated, saying she feared “impending doom.”
CDC director: Feeling of 'impending doom'
Until the entire world is vaccinated, there’s a chance the virus could mutate in ways that evade detection, treatments or vaccines. Keeping a close eye on variants gives vaccine makers a chance to stay ahead of the virus.
A study published this week in Lancet revealed that the AstraZeneca vaccine, not yet available in the U.S., is less effective against the variant first found in Britain.
The good news is that vaccine is 70% effective against symptomatic COVID-19 from the U.K. variant, compared to 80% for other variants. It’s only 28% effective in protecting against asymptomatic disease from the U.K.variant, though, so those who are vaccinated can still spread the disease.
Some existing vaccines are less effective against a variant first detected in South Africa, as clinical trials by Johnson & Johnson revealed. Its vaccine was only 57% effective in stopping symptomatic COVID-19 from that variant.
Pfizer just released new data on 800 volunteers in South Africa and found its vaccine was 100% effective against the variant. Moderna is injecting volunteers with an experimental booster to see if it will offer more protection.
Tracking changes helps with treatments, vaccines
Viruses survive by hijacking the body’s own genetic process to make more virus. The coronavirus is made up of RNA, the same thing our own DNA uses to keep our bodies functioning. When the virus invades a human cell, it can make the cell replicate the virus.
Sequencing took center stage with the Genome Project in 2000, a massive effort to map all of the genes in human DNA. Back then, sequencing genes cost up to $100 million. The price has since plummeted to a few dollars.
Knowing the genetic makeup of a virus has many advantages, including the ability to track changes in the virus and find effective treatments and vaccines.
The specimens come from people getting coronavirus tests at their local pharmacies or health care clinics. The virus is extracted from the swabs stuck up nostrils, which are sent to laboratories with special machines. The sequence itself is made up of only four letters: G, U, A, C, the building blocks of RNA. Scientists can tell when the virus failed to replicate itself exactly by noting differences in the sequence of those letters.
Problems can arise if the mutation changes the proteins on the surface of a virus. Those are the proteins that attach to human cells, allowing the virus to invade. If that protein changes, vaccines and treatments could be less effective.
The ability to sequence has increased dramatically in recent years. Faster technology led to a public-health breakthrough in 2014, when scientists from the Broad Institute at Harvard University used sequencing in West Africa, on early patients of Ebola. By understanding how the virus spread, it made it easier to stop that spread.
By 2018, all states had the ability to sequence. The CDC tests 7,000 samples annually from influenza tests to inform what goes into the annual flu shot.
The U.K. stepped up its sequencing efforts a year ago, soon learning that the coronavirus there was coming from France and Spain more than China, said Ewan Harrison, a deputy director at COVID-19 Genomics UK at the Wellcome Sanger Institute.
When the U.K. in December told the World Health Organization about its disturbing findings on the variant it first detected, the world closed its borders to the U.K.
“That arguably saved lives,” Harrison said. “Now we’re at the point where we pretty much sequence everything we can lay our hands on.”
In the U.S., for years sequencing was largely left to state laboratories and wasn’t a high priority. Although technology for sequencing has improved dramatically in the past decade, some states are still catching up.
Data from GISAID – Global Initiative on Sharing All Influenza Data, a nonprofit database in Germany – indicates the proportion of new coronavirus cases sequenced by states since Feb. 1 has averaged 1.5%, ranging from 0.02% in Oklahoma to 9.7% in Hawaii.
Access to data limited for most scientists
Another problem in tracking variants is how the samples are selected.
Nevada's Pandori said her state started sequencing in April 2020, not to track variants but to track how the virus spread. When there is a COVID-19 cluster, sequencing can tell whether two people who had contact with one another are carrying the identical virus.
In Cambridge, England, an outbreak of coronavirus affected six dialysis patients at a hospital last April. An analysis using sequencing determined the virus wasn’t spreading at the hospital but on the bus bringing patients from their homes. Harrison said the hospital stopped the spread by changing the way patients were transported.
In the U.K., all samples sequenced are uploaded into a public database. While identities are protected, the rest is open and accessible, allowing any scientist to thoroughly analyze it.
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The same is not true in the U.S., or many other countries. Instead, most data about samples is uploaded to GISAID. To encourage scientists to share their data without losing the right to publish their own analysis first, GISAID has strict rules that make it hard to access and share data on gene sequences.
Users also are limited to downloading only 10,000 records at a time. For precise detail, they have to look at each record individually. Then, they are prohibited from sharing the genetic data itself, protecting the intellectual property rights of the scientists who submitted it.
What’s more, the data in GISAID is not random, so without a fuller understanding of how it was collected, the results of any analysis could be biased. Some laboratories may have tested samples from a specific location to trace the origins of a cluster, for example. Some may be specifically testing samples believed to be a variant.
That’s one reason the CDC created its own database in February called National SARS-CoV-2 Strain Surveillance. The federal agency is talking not just to public health directors but also to large private laboratories to encourage them to submit samples in a uniform manner, said Duncan MacCannell, chief science officer for the CDC office that oversees sequencing.
MacCannell said the CDC has a good sense of how widespread variants are nationally, but it’s more difficult to draw conclusions at the state level because the numbers are so small.
“The volume of data that’s being collected every week needs to increase,” he said.
Scarpino at Northeastern University said it’s critical to have adequate data to track the virus at the state and local levels.
“COVID is a local disease,” he said. “It’s not enough to say we know what’s going on in Massachusetts. We need to know what’s going on in Boston. We need to know in the counties, you know, even in the neighborhoods.”
Catching variants of concern early is key
Greater sequencing also would improve the chances of catching a new variant of concern early.
One approach would be to sequence all positive samples from anyone previously infected with COVID-19 or fully vaccinated, said Kelly Wroblewski, director of the infectious disease program at the Association of Public Health Laboratories. That’s becoming a common protocol.
Wroblewski, however, is less concerned than some others about the current state of sequencing.
“I think we can always improve, we can always do more, but I don't have, like, the same urgent concern that we need to catch up,” Wroblewski said. “I think we're heading in the right direction.”
In the U.K., Harrison said he can foresee a day when sequencing will replace testing as a more accurate way to keep ahead of the disease.
When the coronavirus replicates in the body, it can make mistakes and change its structure. The changes more likely to survive are those more resistant to the immune response. That means the longer the virus spreads, the more likely variants will emerge that foil the vaccines.
“As we go further and further into the pandemic, as more and more people have immunity either from being exposed to the virus or from getting vaccinated, I think that's going to put increasing amounts of pressure on the virus to escape (vaccines) through mutation,” said Luca Giurgea, an infectious disease researcher at the National Institutes of Health.
Matthew Memoli, a director at the Laboratory of Infectious Diseases at NIH, said more resistant variants can be the result.
“And when they become dominant, if they’re compatible with the virus continuing to replicate, it becomes a problem,” Memoli said.
Giurgea and Memoli are working together on a new type of vaccine that the virus can’t escape through mutation: a universal coronavirus vaccine. They say they cannot yet predict when it might be available.
David Heath is a reporter on the USA TODAY national investigations team. Contact him at email@example.com or @davidhth, or on Signal at (240) 630-1962.