A variant of the coronavirus that emerged in mid-2020 and emerged to become the dominant strain in California not only spreads faster than its predecessors, but also avoids antibodies generated by COVID-19 vaccines or previous infection and is associated with serious illnesses and death, researchers said.
In a study that helps explain the state’s dramatic rise in COVID-19 cases and deaths – and portends more problems ahead – UC San Francisco scientists said the group of mutations that characterizes the locally grown strain should mark it as a “variant of concern” on a par with those in the UK, South Africa and Brazil.
“The devil is already here,” said Dr. Charles Chiu, who led UCSF’s team of geneticists, epidemiologists, statisticians and other scientists in a comprehensive analysis of the new variant, which they call B.1.427 / B.1.429. “I wish it were different. But science is science. “
Californians, along with the rest of the country, have been preparing for the emergence of a variant of the UK’s most transmissible coronavirus, known as B.1.1.7. But they should know that a rival strain that is likely to be equally worrying has already set in and is likely to be responsible for 90% of the state’s infections by the end of next month, said Chiu, a doctor and infectious disease researcher.
The UK and California variants are equipped with improved capabilities, and the likelihood that they can circulate in the same population increases the spectrum of a return to increased infections and deaths, said Chiu. It also opens the door to a “nightmare scenario”: that the two viruses will meet in a single person, exchange their mutations and create an even more dangerous strain of the SARS-CoV-2 virus.
New evidence that the California variant may make people sicker and vaccines less effective should spur more intensive efforts to reduce infections, said Chiu. This should include both public health measures, such as masking and limits on public activities, and a rapid vaccination campaign, he added.
The new analysis is being revised by the public health departments of San Francisco County and the state, which collaborated on the new research. The publication is expected to be published later this week on MedRxiv, a website that allows new research to be shared before its formal publication.
Over five months from September 1, the California strain, which is sometimes referred to as 20C / L452R, came out of complete obscurity to account for more than 50% of all coronavirus samples that were subjected to genetic analysis in the state. Compared to the strains that were most prominent here in the early fall, the new strain appears to have an improved ability to spread, said Chiu.
Exactly how much more communicable the California strain remains an open question, he added. But the evidence that it is more contagious comes from several sources.
Samples collected in several counties, and using a variety of collection methods, suggest that the variant is 19% to 24% more transmissible. But in some circumstances, its advantage was much greater: in an outbreak at a nursing home, B.1.427 / B.1.429 spread at a rate six times higher than its predecessors.
The researchers also discerned uniform patterns of expansion of the variant across state counties. When infection rates increased, they usually did so in conjunction with the growing evidence of the presence of the California strain.
The increased propensity of the variant for propagation was also evident in the laboratory results. An analysis of viral samples from across the state showed that, compared to people infected with other strains of SARS-CoV-2, those who were infected with the California strain had viral loads twice as high in the nasopharynx.
This, in turn, made it very likely that each person infected with the new strain would infect more people.
The B.1.427 / B.1.429 genome includes three mutations that affect the crucial spike protein, which the virus uses to infiltrate human cells and convert them into factories for its own production. One of these three mutations, dubbed L452R, affects the so-called receptor-binding domain, helping the virus to bind more tightly to target cells.
This adaptation was not seen in variants of the coronavirus that caused concern elsewhere.
In a UCSF laboratory, scientists found that the L452R mutation alone made the California strain more harmful as well. A coronavirus designed to have only this mutation was able to infect human lung tissue at least 40% more readily than circulating variants without the mutation. Compared to so-called wild-type strains, the modified virus was more than three times more infectious.
In the laboratory, the California strain also proved to be more resistant to neutralizing antibodies generated in response to COVID-19 vaccines, as well as a previous infection by coronavirus.
Compared to existing variants, the reduction in protection was “moderate … but significant,” the researchers said.
The coronavirus strain that is now dominant in South Africa – and which has raised concerns about how to escape the immune system’s defenses – has been shown to reduce the effect of neutralizing antibodies by a factor of 6.2. With the California strain, the effect of these antibodies was reduced by a factor of two.
“I predict that over time this will have an effect on vaccination,” said Chiu. Although the magnitude of the effect varied from sample to sample and was less pronounced than with the South African strain, “it is still worrying,” he said.
Ominously, the new study also suggested that the California variant could be more virulent.
This observation is based on the medical records of 324 patients hospitalized at UCSF, a relatively small sample. Still, the researchers found that 21% of those patients infected with B.1.427 / B.1.429 were more likely than their counterparts to have been admitted to the ICU and were 11 times more likely to die. This finding continued even after the researchers adjusted the differences in patients’ age, sex and ethnicity.
However, Chiu cautioned that this increased risk of death may not be a sign that the variant is inherently more lethal. Instead, it may simply be a reflection that its increased transmissibility has made hospitals so overburdened and health resources so scarce that more deaths are the result – especially in Southern California.
Dr. Marc Suchard, an infectious disease screening expert at UCLA, said some of the team’s findings are likely to be refined as more virus samples are genetically sequenced and more data comes to light.
“It remains extremely important that we actively sequence the virus as cases are diagnosed in our state,” said Suchard, who was not involved in UCSF’s work. “I am happy to see this collaboration between academics and public health departments in California to identify the emergence of a previously unidentified lineage.”