US lags in tracking coronavirus variants
Slow rate of gene sequencing, limited access to data hurt effort
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 new 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 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 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 USA go only to researchers, not to those who got tested. That could become a problem if a variant demands a different approach to treatment or proves resistant to vaccines.
Public laboratories in the United Kingdom sequence a third of positive coronavirus tests, according to the COVID-19 Genomic UK Consortium. They discovered the B.1.1.7 variant in September. On Dec. 14, scientists reported this variant was far more contagious and could be more lethal.
Until recently, only a minuscule fraction of samples in the USA 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 midFebruary. The CDC tries to sequence at least 7,000 positive test samples a week, about 2% of new cases.
“We’d really like to get that into double digits or more,” said Joel Sevinsky, founder of Theiagen Genomics, which helps health officials track outbreaks.
By early January, laboratories in the USA had detected 76 cases of the variant first detected in Britain, about 5% of new coronavirus cases. Since then, the variant has exploded. Last week, it made up about 32% of new cases. Another fast-spreading variant, B.1.526 – 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 asked 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, the number of U.S. cases rose, and some public health officials worry the U.K. variant could trigger another surge. They are concerned the New York variant may be resistant to vaccines.
CDC Director Rochelle Walensky urged all Americans to get vaccinated, saying she feared “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 the AstraZeneca vaccine, not available in the USA, is less effective against the variant found in Britain.
That vaccine is 70% effective against symptomatic COVID-19 from the U.K. variant, compared with 80% for other variants. It’s only 28% effective in protecting against asymptomatic disease from the U.K.variant, so those who are vaccinated can still spread the disease.
Some vaccines are less effective against a variant that was first detected in South Africa, as clinical trials by Johnson & Johnson revealed. Its vaccine was 57% effective in stopping symptomatic COVID-19 from that variant.
Pfizer released 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 whether it will offer more protection.
Tracking changes
Viruses survive by hijacking the body’s genetic process to make more virus. The coronavirus is made up of RNA, the same thing DNA uses to keep our bodies functioning. When the virus invades a human cell, it can make the cell replicate the virus.
Knowing the genetic makeup of a virus has many advantages, including the ability to track changes and find effective treatments and vaccines.
Specimens come from people getting coronavirus tests at pharmacies or health care clinics. The virus is extracted from the swabs stuck up nostrils and sent to laboratories. 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 proteins attach to human cells, allowing the virus to invade. If that protein changes, vaccines and treatments could be less effective.
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, learning that the coronavirus 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. told the World Health Organization in December about the variant it 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 USA for years, sequencing was largely left to state laboratories and wasn’t a high priority. Some states are still catching up.
Data from GISAID – the 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
Another problem in tracking variants is how the samples are selected.
Pandori said Nevada 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 carry 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. Though identities are protected, the rest of the information is accessible, allowing any scientist to analyze it.
The same is not true in the USA or many other countries. 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 are limited to downloading 10,000 records at a time. For precise detail, they have to look at each record individually. They are prohibited from sharing the genetic data itself, protecting the intellectual property rights of the scientists who submitted it.
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 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 early
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.