A patient receives a booster shot at a pop-up clinic held at New Providence Baptist Church in San Francisco’s Ingleside neighborhood. New coronavirus subvariants are reducing the ability of vaccines to prevent infection and can compromise treatments.
More than previous versions of the coronavirus that causes COVID-19, the emerging BQ.1, BQ.1.1 and XBB subvariants — descendants of the dominant omicron strain — are capable of getting around the immunity gained from vaccination or prior infection, studies warn.
Their wily evasiveness makes approved vaccines less effective at preventing infection and jeopardizes treatments meant to protect immunocompromised individuals, experts said, though noting that the latest booster is still better than no booster at all.
Like the rest of the country, California is experiencing a sustained rise in COVID cases and hospitalizations. Across the U.S., the BQ.1 and BQ.1.1 subvariants have rapidly become the leading sources of COVID-19, accounting for 68% of new infections, according to the most recent data from the Centers for Disease Control and Prevention. XBB, the subvariant with the most key mutations, currently makes up less than 5% of cases nationwide.
The concern among scientists is that the BQ and XBB subvariants are “the most immune evasive yet,” said Nadia Roan, a senior investigator at Gladstone Institute of Virology, a Bay Area-based biomedical research center. This means they’re better able to slip past the immune system’s frontline defenses and infect an individual.
“It’s not unexpected that these new variants have evolved ways to become more immune evasive, but I do think it means that we should be more vigilant,” Roan said.
Like the original BA.1 omicron and later descendants such as the BA.2 and BA.5 that caused last summer’s surge, the new BQ and XBB subvariants are more transmissible than the original virus that was responsible for kicking off the pandemic in 2020. Fortunately, they also seem to provoke less severe illness.
Singapore, which experienced a surge in XBB-related cases in recent months, reported a 30% lower risk of hospitalization with the omicron XBB subvariant compared to the omicron BA.5 subvariant, according to a Singaporean government notice — although the Asian city-state has a much higher vaccination rate than the U.S.
So far, “We’re not seeing a huge upsurge in hospitalizations and deaths,” said Stanford Medicine Senior Associate Dean Yvonne Maldonado. “What we’re seeing is lots of people getting infected and then, occasionally, some people are being hospitalized and dying.”
Roan and Maldonado cautioned that the higher chance of infection means an increased possibility of acquiring long COVID, a still poorly understood phenomenon marked by persistent symptoms. It also worries high-risk individuals for whom infection is more likely to lead to severe illness.
Higher caseloads could also further strain Bay Area hospitals, which are already struggling with the “tripledemic” of COVID, flu and respiratory syncytial virus.
The BQ.1, BQ.1.1 and XBB subvariants have “alarming antibody evasion properties,” according to a Columbia University study published last week. Neutralizing antibodies are among the immune system’s first line of defense against infection: They prevent the virus from entering the cell and are often assessed on how well they protect against infection, Roan said.
The COVID-19 virus enters human cells by latching onto a protein on the surface called the ACE2 receptor, Roan said. On the COVID-19 virus, there’s a particular region on its “spike” protein called the receptor binding domain, or the RBD, that allows it to “dock” to the human cell’s ACE2 receptor and enter the cell, where it replicates.
Neutralizing antibodies prevent infection by binding to the RBD and making the ACE2 receptor essentially invisible to the COVID virus, Roan said.
But the newest COVID subvariants have RBD mutations, rendering neutralizing antibodies generated by vaccination, prior infection or a combination of the two less effective. The XBB subvariant has seven mutations in its RBD region, the highest number observed so far. BQ.1.1 has six mutations in the RBD region, while BQ.1 has five.
At the beginning of the pandemic when few people had immunity, the virus primarily evolved to become more transmissible, which means it was better able to get to a host first, Maldonado said. Now, as more people gain immunity via infection or vaccination, the numerous variants of the COVID-19 virus are facing different evolutionary pressures to gain dominance, Maldonado said.
The good news is that the immune system has other defenses that are likely to remain effective against the new subvariants, such as B and T cells that are our “protectors against severe disease,” said UCSF infectious disease expert Dr. Monica Gandhi. T cells still respond “substantially” to the omicron spike protein, according to a Korea Virus Research Institute study from May, and in general are more resistant to viral mutations, Roan says.
While antibody levels wax and wane with time, the long-acting B cells serve as memory banks to produce antibodies when needed, Gandhi said. T cells help B cells make antibodies and help recruit cells to attack the pathogen directly, she added.
The new subvariants are a sign of how fast the COVID-19 virus evolves: The new bivalent booster, just approved this August, is already having trouble keeping up.
BQ and XBB present “serious threats to the efficacy of current COVID-19 vaccines,” according to the Columbia study. A University of Texas Medical Branch study published Wednesday came to similar conclusions, finding “low” neutralization of BQ.1.1 and XBB from the updated booster.
The new shot is an enhanced version of the COVID-19 vaccine that targets both the original virus and omicron. But compared to its protection against the omicron BA.5 subvariant, the bivalent booster is four times less effective against the BQ.1.1 subvariant and eight times less effective against the XBB subvariant, said Chaitanya Kurhade, an author of the University of Texas study.
Uptake of the bivalent booster shot has also been abysmal: Less than 13% of eligible Americans have received it, according to CDC data.
Still, despite its weakened efficacy, the new booster is better than the original vaccine at fending off omicron viruses: The updated shot can increase protection against symptomatic infection by up to 56% compared with receiving at least two doses of the original vaccine alone, according to CDC data published this week. Specifically against the BQ.1.1 subvariant, the bivalent booster is five to 10 times more effective than the original booster, according to several preprint studies.
Kurhade noted that even if the bivalent is less effective in preventing infection, it can still help prevent serious disease because vaccines also trigger high levels of B and T cell immunity.
“Immunity is not an all-or-nothing kind of thing; it’s not like you have it or you don’t. Getting the bivalent right now is important because it gets you closer to having better immunity,” Roan added.
The new COVID subvariants are most worrying for immunocompromised people as hard-won treatments become less effective in the face of BQ.1, BQ.1.1 and XBB.
One crucial class of drugs is monoclonal antibodies, which imitate natural antibodies produced by people with regular immune systems. Once hailed as a COVID “miracle,” they are no longer an option: Last week, the U.S. Food and Drug Administration paused authorization for the last monoclonal antibody approved for COVID-19 treatment because it was not able to neutralize BQ.1 and BQ.1.1.
Part of the problem is that monoclonals take time to develop, Maldonado said. “By the time they make another batch that matches say, XBB or the BQs, will those still be circulating? We don’t know the answer to that,” she said.
Immunocompromised individuals can still turn to Evusheld, a preventative shot of monoclonal antibodies injected before COVID-19 exposure. But Evusheld can be difficult to obtain, and it’s also less effective against the newest subvariants, according to an FDA notice.
Encouragingly, antiviral drugs such as Paxlovid and remdesivir are still effective against BQ.1.1 and XBB, according to a Wednesday research letter in the New England Journal of Medicine.
In addition, a technique called convalescent plasma, in which antibodies are taken from individuals who’ve recently been infected or vaccinated and then transferred to immunocompromised people, still “potently neutralizes” BQ.1.1 and XBB.1, according to a Johns Hopkins study published last week.
Convalescent plasma is a logistically challenging treatment, Roan cautioned. But its strength is that convalescent plasma from someone infected with a different strain of the virus can still be effective against BQ.1.1 and XBB.1, said David Sullivan, an author of the Johns Hopkins study.
Ultimately, the goal is for scientists to pinpoint the most recent strain every year so newly updated boosters can neutralize whatever subvariant of the virus is in circulation, Kurhade said. “The recommendation will always be to get the most updated booster,” Kurhade said.
“Of course, the big trick is, how do you predict what’s going to be circulating four or five months down the road?” Maldonado said.
Claire Hao is a San Francisco Chronicle staff writer. Email: claire.hao@sfchronicle.com, Twitter: clairehao_
Claire Hao is A Hearst Reporting Fellow who joined the San Francisco Chronicle in 2022. She is a recent graduate of the University of Michigan, where she forayed into journalism at the student newspaper. Since then, she has interned on the news desks of Bloomberg Law and The Chicago Tribune as well as on the editorial board of The Washington Post. She was also the 2021 editor-in-chief of her college paper The Michigan Daily.
Having lived in Michigan for most of her life, Claire is really excited to begin her professional career by exploring two different cities. In her free time, Claire enjoys reading, writing, running and playing the guitar.
