Scientists are working to trace the virus’ origin, changes and spread by analyzing the disease’s genetic sequence
Tracking tiny mutations in the novel coronavirus, Bay Area scientists are revealing how the deadly pathogen might have gained a foothold in California — and how it is now wreaking havoc across the region.
By comparing genomes, the team has discovered that the virus that spread through the Grand Princess cruise ship — responsible for cases of COVID-19 infection in multiple Bay Area counties — is almost identical to the virus found in Washington state, where 40 people have died.
This suggests, although doesn’t prove, that the ship’s virus may have been inadvertently
introduced by a traveler from our neighbor to the north, said Dr. Charles Chiu, a professor of laboratory medicine at UC San Francisco, who directs the project.
The exact circumstances of this likely jump to the San Francisco-based ship from the Seattle area, where the virus was first detected, cannot be determined from the genetic data alone. The ship departed to Mexico on Feb. 11 and returned
Feb. 21 with a sick passenger from Placer County who later became the first Californian to die from the disease. Crew members, too, became ill on that journey.
Once aboard the ship — and we don’t know who brought it there — the virus also spread to Bay Area passengers, who unwittingly brought it home, potentially fueling the region’s outbreak.
Among Santa Clara County’s 91 cases are at least two passengers from that voyage. Of Alameda County’s 10 cases, two are linked to the ship; one was a passenger and the other was a spouse. A Santa Cruz resident, now sick, was on the cruise. At least three of five Marin County cases are linked to the ship; one was a passenger and two others share his home. Two of Contra Costa County’s 29 cases were aboard the Grand Princess. In the 32 San Mateo cases and 28 San Francisco cases, the ship’s role in spreading disease has not been clarified by authorities.
Seven other counties report infections from the Grand Princess cruise. They include four people in Placer, two in Sonoma and at least one in Fresno, San Joaquin, Madera, Stanislaus and Ventura counties.
It is possible, Chiu notes, that the Washington and California outbreaks are unrelated and that the virus took independent routes internationally from outside the U.S. to both states. But that seems less likely because their genetic sequences are so closely matched.
“The simplest explanation is that the cases in the cruise ship were introduced from the cases in Washington state,” he said.
Now his team of medical detectives is analyzing the gene sequences of the viruses in Santa Clara, San Mateo, San Francisco and other Bay Area counties.
Despite aggressive public health measures, the region’s case count has skyrocketed — from just one case on Jan. 31 to more than 100 cases on Thursday.
The team’s goal is to map the journey of the mysterious virus from town to town by tracking small changes in its genes as it reproduces.
This can guide public health measures, helping reveal hotspots. It also will boost vaccine work, showing which regions of the viral genome don’t change over time and can be targeted.
The same technique was used by global epidemiologists to trace the start of the Ebola and Lassa fever outbreaks. It revealed, for instance, that a deadly Ebola outbreak in Sierra Leone started from a single funeral.
In the UCSF project, the lab first tested a virus from a Sonoma County passenger who boarded the first leg of the Grand Princess cruise, which sailed from San Francisco to the Mexican Riviera and back. That test showed that the virus lived on the same branch of the genetic family tree as the cluster of Washington state cases.
Then the lab analyzed viruses from six of the 21 sick passengers aboard the second leg of the cruise, which sailed from San Francisco to Hawaii and back. Those viruses also matched those from Sonoma and the Washington state cluster, the test showed.
The virus from the Placer County patient — who may have been the person who brought the disease to the ship — has not yet been studied; the state is now seeking to obtain a sample.
In a third project, the UCSF lab tested an unrelated “mini-cluster” in Solano County involving a woman treated at Vacaville’s Northbay Vacavalley Hospital and then was rushed to UC Davis. She was the first case of “community transmission” reported in the U.S. — that is, transmission of the infection without an identified exposure such as contact with a returning traveler. Her virus jumped to two health care workers.
She was not on the cruise, and her virus looks different from that strain. It is not known how or where she contracted the virus.
“There is not a single strain circulating widely in California,” said Chiu. “Multiple strains are circulating.”
The UCSF mapping project is applauded by Trevor Bedford, an associate professor at the Fred Hutchinson Cancer Research Center and the University of Washington.
“One of the most powerful aspects of genomic data for COVID-19 is the ability to make connections between seemingly disparate outbreaks,’” tweeted Bedford, who is analyzing the march of the virus through Washington state.
“As viruses from elsewhere in the U.S. get sequenced, we’ll learn about how connected these outbreaks are,” he said.
The samples are provided by the Viral and Rickettsial Disease Laboratory of the California Department of Public Health, which is rushing to process specimens from the rising tide of illness.
From Chiu’s lab at UCSF’S Mission Bay, a staffer drives to the Richmond-based lab to pick up precious genetic extracts of the new virus.
Back at the UC lab, sophisticated machines spit out data onto a computer screen in the form of a long list, in order to assemble the letters that make up the sequence of the virus’ genetic code.
Then the codes are mapped on a family tree and compared. As in any family tree, viruses that look alike are thought to be closely linked.
A global pedigree of COVID-19 viruses is being built, although it’s incomplete. Using 169 publicly shared COVID-19 genomes, scientists at Bedford’s team at the University of Washington and colleagues at Biozentrum in Basel, Switzerland, are tracking the virus’ journey around the world.
Scientists are witnessing the growing branches of the family tree, as diversity emerges. Like all viruses, COVID-19 evolves over time through random mutations.
Over the length of its 30,000-base-pair genome, the virus accumulates an average of about one to two mutations per month, scientists say.
At the very beginning of the outbreak in Wuhan, China, the viral genomes from initial patients were identical, suggesting that the virus — which originated in animals — jumped to humans just once. Every sequenced virus in the global family tree seems to share this common ancestor, which emerged sometime between mid-november and mid-december.
In the U.S., the nation’s first case was reported in Snohomish County, Washington, of a man in his 30s who had returned from Wuhan on Jan. 15 and became sick several days later. Officials tested two dozen people who had contact with him, but tests all came back negative.
Six weeks later, the virus was found in a Snohomish County teenager. It looked like a direct descendant of the first case, according to Bedford’s lab.
If the virus spread undetected in Washington for six weeks, that means anywhere from 150 to 1,500 people may have contracted it, with about 300 to 500 people the most likely range, Bedford said. This is called “cryptic transmission” and is very dangerous.
Unlike in California, analysis of 23 of Washington’s “community cases” shows that they all fall into the same transmission chain, Bedford reported Thursday.
No one knows, but perhaps one of these Washington residents boarded the Grand Princess cruise or infected a Californian who did.
The lab’s more ambitious analyses of a much broader swath of Bay Area cases will give us a significantly better picture of the scale and identity of the growing outbreak.
“Are the multiple strains currently in these communities? Is there ongoing transmission that we’re unaware of?” asked Chiu. “This information can inform our public health efforts.”