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Local health officials are grappling with tracking coronavirus variant data as COVID-19 cases surge in California and nationwide.
Timeliness is the most significant limitation in tracking the data because of the turnaround time involved in whole genome sequencing, said Dr. Matt Willis, Marin County’s public health officer. Genome sequencing is the process of decoding a virus’ genes, which helps identify variants.
After a positive COVID-19 sample is recorded and sent to a lab for sequencing, it can take weeks before labs report variant information back to local health departments.
“You have to look into the past to see what’s changing,” Willis said about variant data. “Intuitively I think people think the most recent is the most important data. Unfortunately, the most recent data also represents the most incomplete data.”
Marin is one of three Bay Area counties to publish localized variant data. Others are working to streamline the data they receive before sharing with the public.
Variant data helps scientists understand how the virus is spreading within communities, which drives the public health decisions that affect our daily lives.
Finding the variant
Genomic surveillance allows scientists to monitor variants – like the delta variant – of the SARS‑CoV‑2 virus that causes COVID-19 and how they affect public health.
The Stanford Clinical Virology Lab, which does COVID-19 testing for Stanford Health Care and Stanford Children’s Health, is one of the labs that performs whole genome sequencing on COVID-19 samples.
The lab has developed an assay, a screening test that can quickly identify a common variant of concern or variant of interest, said Dr. Benjamin Pinsky, the lab’s medical director.
Then, the lab does whole genome sequencing on some or all the samples to confirm the lineage of the mutation or figure out if there are new mutations.
The sequencing process involves applying the COVID-19 samples to a sequencer, which provides reads of the virus’ genetic material.
These reads are then compared to the genetic material of an original reference strain, like the one that originated in Wuhan, China.
Finally, the lab uploads the sequencing information to GISAID, the international database for tracking and sharing genetic information from the influenza virus and the coronavirus that causes COVID-19. Once GISAID accepts the sequence, labs can report the variant information back to the relevant public health departments.
What are virus mutations and how do they arise?
According to the Centers for Disease Control and Prevention, mutations are “changes in the genetic code of a virus that naturally occur over time when an animal or person is infected.”
Dr. Benjamin Pinsky, medical director of the Stanford Clinical Virology Lab, said that mutations are simply differences in the nucleotides of a virus, which are the building blocks of the virus’ genes.
These genetic variations can change the structure of a virus’ proteins, which are built from amino acids.
“The amino acid changes that we’re most concerned about are the ones that are in the spike protein, because spike is what mediates entry of the virus into ourselves and binds to ACE2, which is the cellular receptor for SARS-CoV-2,” Pinsky said.
Some of the mutations to the spike protein appear to allow the virus to bind more tightly to the receptor on human cells, which may make it more contagious or transmissible.
“From a technical standpoint, it is a reasonable amount of work to get these samples out and it’s, I would say, relatively laborious. It’s not a rapid test for sure,” Pinsky said. “But those are things that can be overcome.”
In California, more than 30 labs have submitted sequence data to GISAID as part of a statewide initiative.
Called COVIDNet, the initiative began in May 2020. The California Department of Public Health coordinates a network of state and local labs such as the Chan Zuckerberg Biohub, academic labs like those at University of California campuses and the Scripps Research Institute.
But the sequencing process takes several days, and two to three weeks can pass before variant information gets back to local health departments.
The state health department aims to sample about 10 percent of positive COVID-19 samples.
In July, 10 percent of California cases were sequenced, according to the CDPH website.
In August, so far 3 percent of cases were sequenced and these numbers will likely increase as more data becomes available.
The limited sample size is another limitation of variant data. Only a subset of COVID samples is sequenced, so available data do not represent all the infections caused by certain variants.
Plus, that subset is not always chosen at random.
State health officials said most departments aim to sequence “severe cases that result in hospitalization and/or death, post-vaccination infections, response testing to outbreaks, and samples from residents of long-term care facilities.”
Variant data guides public health
This focus on sequencing severe cases or outbreaks led Marin County to discover the delta variant in its population earlier this year, according to Willis, the county’s public health officer.
“Starting in May we had an outbreak in Fairfax, one of our towns, where we saw an increased number of cases,” Willis said. “We weren’t able to find the usual smoking gun that goes along with a cluster of rapid rising cases.”
What looked like “normal” social interactions were more frequently leading to transmission, he said. When positive samples from the outbreak were sequenced, the delta variant was detected.
It was one of the first cases of COVID-19 infection caused by the delta variant reported in the Bay Area, Willis said.
Since then, Marin County has aimed to sequence about half of its positive COVID samples.
In the most recent collection week at beginning of August, the delta variant represented 90 percent of all the COVID samples sequenced that week in Marin County.
This data is published online, along with the disclaimer that reporting may lag up to 21 days and that the data only shows a fraction of sequenced results. Moreover, since not all positive samples are sequenced, the data “may not fully represent the prevalence of circulating variants in the community.”
Despite these limitations, Willis said the department hopes publishing variant data will help the public understand the “why” behind official public health recommendations.
“We have always been saying that at every step of this pandemic we need to be adapting our strategies to the science, to the data and to what’s changing,” Willis said. “It helps keep the trust and credibility in public health when people can see for themselves what that change is, when they can see for themselves, in this case, how the delta variant really has become in visible ways – graphically visible ways – the dominant strain.”
Vaccinations are key
In Contra Costa County, health officials are tracking variant data and working to get that data reported in the same system.
While the county has not yet published local variant data, officials have been tracking how case rates differ between vaccinated and unvaccinated populations.
And the data is clear: the case rate for unvaccinated people is higher than it is in vaccinated people. In mid-August, the unvaccinated case rate was 58 cases per 100,000 residents compared to 11 per 100,000 for vaccinated residents.
What can we do to slow down the spread of the virus and protect ourselves from variants?
Dr. Sefanit Mekuria, Contra Costa public health deputy health officer, said that many of the preventive measures remain the same: Stay home if you’re sick. Get tested if you have COVID-19 symptoms. Wear a mask indoors. Get vaccinated.
“We do know vaccines are really effective in preventing severe disease, hospitalizations and death,” Mekuria said. “Vaccination is the one thing that is the biggest protection even against variants.”
Vaccinations can also help slow down the spread of the disease, making it harder for other variants to form, she said.
“And we’ve seen in populations in the United States that populations that have really low vaccine rates have been hit very hard by the delta variant with really, really high case rates,” Mekuria said.
In this July 2021 video, Marin County health experts Dr. Matt Willis and Tracy Lam-Hine discuss Whole Genomic Sequencing and how Marin County Public Health uses the genomic surveillance to track and link COVID-19 variant cases in the county: