San Francisco Chronicle - (Sunday)
Tight race between variants, vaccines
Shots may not come soon enough to prevent surge
In the fall, as California braced itself for what public health authorities promised would be the darkest months of the pandemic, there was a hint of hope in the message: This surge might be the last.
Even in the grim final weeks of the year, vaccines were rolling out and everyone knew that cases and hospitalizations would finally fall in the new year. The next potential super-spreading holidays would be months away. It seemed possible that California and the rest of the country could conquer the virus before a fresh wave of cases swelled.
And then the variants ar
rived. A highly infectious mutant virus grabbed headlines in late December as it swept across the United Kingdom, and by Dec. 31 it was in California. More reports soon followed.
“We would all love to be able to say it’s all downhill from here, but we can’t say that based on these variants,” said Dr. Nicholas Moss, the health officer in Alameda County, which reported its first six cases of the variant from the U.K. last week. “The virus is adapting more quickly than we initially had thought.”
Public health experts have said for weeks that the United States is in a race against variants, to vaccinate as many people as possible before new mutations of the coronavirus cause even more widespread disease or make the vaccines less effective.
That race, they say, is getting tighter. “The chance for another surge in California is real,” Dr. Mark Ghaly, secretary of California Health and Human Services, said at a news briefing last week.
Reports suggest that a highly infectious variant of the virus that rampaged through the United Kingdom already has a strong foothold in Southern California and could become dominant there within weeks — a situation that could lead to another uptick in cases before the region has recovered from the last surge. And across the state another pair of new variants is spreading fast as scientists try to determine if they are more infectious or able to partly evade vaccines.
Vaccinations, even with the state’s bumpy, inconsistent rollout, may help temper another resurgence in cases. But they may not come fast enough to prevent another wave altogether, especially because the older adults being targeted are not the ones generally driving new cases. Some infectious disease experts have suggested reorganizing California’s vaccine priority list to emphasize younger adults who are responsible for most of the spread of disease, but experts say that’s unlikely. “We don’t know what these variants are going to do. But they’re going to keep coming, I think that’s a certainty,” said Dr. Art Reingold, a UC Berkeley epidemiologist who has consulted on California’s vaccine planning. “It means we need to redouble our prevention efforts, and get as many people vaccinated as quickly as possible. But should we change the target for how we use limited number of doses? I don’t think that’s going to happen.”
There are at least two variants of concern now showing up widely across California. The variant from the U.K. — called B.1.1.7 and known to be about 50% more infectious than the original virus from China — is quickly gaining traction, primarily in Southern California. On Jan. 11, only 32 cases had been reported in California. By Feb. 4, that number had increased nearly sixfold to 187, according to the Centers for Disease Control and Prevention.
Some of the increase is undoubtedly because of rampedup surveillance. But it’s also a sign that the variant is spreading fast, infectious disease experts said. A San Carlos company that helps conduct genomic sequencing for the CDC reported last week that it expects the variant to make up the bulk of cases in Southern California in a few weeks, and across the country in a few months. The CDC has said it may dominate nationwide in March.
If the variant does explode across Southern California, it will almost certainly take off in the Bay Area too, infectious disease experts say. The region reported its first B.1.1.7 cases 10 days ago, and last week UC Berkeley said that two of its students, who had been almost entirely off campus, were among the six cases identified in Alameda County. Moss said he doesn’t believe there’s yet community spread of the variant, but he didn’t know where the individuals had been exposed to it.
Meanwhile, a pair of Californiabred variants — known as B.1.427 and B.1.429 — also are being identified with more frequency, with nearly 1,000 cases reported so far. Scientists don’t yet know whether these variants also are more infectious than the original virus or have mutations that could make the vaccine less effective. They’re conducting those studies now.
Two variants discovered in South Africa and Brazil are believed to be less responsive to vaccines, according to multiple studies; there’s no such evidence yet for the California variants. At least one vaccine manufacturer is working on a booster that could be administered if any variants develop more significant resistance.
Both California variants, which are genetically very similar, became much more widespread during the fall and winter surge, suggesting they could have been a factor. One accounts for up to 40% of the California cases sequenced recently at one Bay Area lab. Both have been tied to large outbreaks — including a major cluster at a Kaiser hospital in Santa Clara County that led to more than 90 infections — which is another hint that they may be more infectious.
“It’s kind of guilt by association, not science,” said Dr. Jeffrey Golden, vice dean of Research and Graduate Education at CedarsSinai in Los Angeles, where one of the two variants was identified; the other variant was found by UCSF scientists. “But the coincidence of (the variants) coming up so rapidly and becoming such a high percentage right when there’s a huge surge is a little suspicious. More than a little suspicious.”
And both of the California variants have a critical mutation that could make them better able to fend off immune attacks, including those generated by vaccination. Golden said the variant his team identified already shows signs of not responding to one of the experimental monoclonal antibody treatments used for COVID19.
Dr. Charles Chiu, director of the UCSFAbbott Viral Diagnostics and Discovery Center, has done genomic sequencing on a few rare cases of people becoming infected after being fully vaccinated; the vaccines are about 90% to 95% effective, which means a small number of postimmunization cases are to be expected. In the samples he’s studied, the people were infected with the B.1.429 variant his lab identified.
That may just be coincidence, he said — with the vaccines so new, there are too few cases of postvaccination infection to draw conclusions. Still, “it is a little worrisome,” he said. The possibility of reduced vaccine effectiveness is “something which urgently needs to be explored.”
And what if the California variants start mingling with the variants from the U.K.? One very slim possibility is an individual becoming infected with two variants at once, then those variants merging into a new one, with the combined mutations, as they replicate within shared cells. That’s highly unlikely, infectious disease experts said. But scientists in the U.K. have started thinking about the possibility, in terms of their variant and one found in South Africa that is known to be at least somewhat resistant to vaccines.
In California, experts said they don’t know what will happen as the new variants spread more widely. Perhaps they’ll simply coexist, or one variant with an evolutionary advantage could end up dominating.
The rapid increase in variant cases, though, underscores the urgent need for more surveillance. Helix, the San Carlos genomic sequencing company, escalated its hunt for new variants as concerns grew over B.1.1.7 in the U.K. Along with San Diego sequencing firm Illumina, it started contracting with the CDC a few days before Christmas and had identified its first B.1.1.7 case by the end of the year. The companies have identified 122 cases of B.1.1.7 in California so far.
James Lu, chief executive of Helix, said the United States would need to sequence about 5% of its coronavirus cases to quickly identify new variants or efficiently track the spread of known ones. At the moment, the country is sequencing fewer than 1% of all cases.
“You’ll detect new variants” at that level, Lu said. “It’s just a question of how long you’re willing to wait to see a signal. And in my view you want to know as soon as possible.”
As of the end of January, the United States had submitted about 90,000 genomic sequences — or about 0.3% of the 24 million cases total — to an international database, known as GISAID. The United Kingdom, which is among the world leaders in coronavirus sequencing, had submitted 195,000 sequences, or about 5% of its total cases.
California has submitted about 12,000 sequences to GISAID, second in the United States to Texas’ 15,300 submissions. California has sequenced about 0.4% of its cases and Texas about 0.6%.
“The total amount of sequencing in the United States is pitiful. Good for Texas, but it’s not hard to be No. 1 right now,” said Dr. Joe DeRisi, copresident of the Chan Zuckerberg Biohub in San Francisco, which does about 45% of the genomic sequencing of coronavirus in California.
He noted that demand for sequencing has climbed dramatically since the new variants started to surface, which is reflected in the GISAID numbers too: The United States submitted more than a third of its total sequences to the database in January alone.
Despite frustration with the pace of sequencing, and concerns over the spread of new variants and the rocky vaccine rollout, infectious disease experts such as DeRisi said they remain hopeful that the end is in sight. “There’s a lot of reasons to be optimistic,” he said.
The vaccines, even if they lose some effectiveness against new variants, are still very powerful, including three that have not yet been approved in the United States but may get emergency authorization in the coming weeks or months.
Cases are dropping, as are deaths. Slowly, the vaccination numbers are improving.
“There will be a time that we get back to normal,” DeRisi said. “But there has to be patience and some discipline in what we do to get to that point. If we lack that, we run the risk of more stumbling blocks.”
San Francisco resident Denny Smith, 68, got his first dose of vaccine Monday, and he said he’s eager to go to movie theaters and parties and hug and kiss his friends hello. But even though he’ll be fully vaccinated in about six weeks, he knows he’ll still have to practice caution, including wearing masks and keeping his distance from others, for many more months.
Now he wonders whether the variants will be yet another hurdle toward getting back to normal.
“I go out every day, or else I’d go crazy. I wear a mask. I’ve been pretty meticulous. But this staying physically distant is really hard for me,” Smith said. “I’m worried that this is going to affect us for a very long time.”