Initial data suggest that a coronavirus variant first detected in California may be more transmissible, possibly causing a more serious disease and impacting the vaccine’s effectiveness.
The study authors are awaiting approval from public health departments to publish a prepress, although Dr. Charles Chiu, co-author of the study and professor of laboratory medicine at the University of California, San Francisco, shared and the findings for Fox News.
“I am worried, worried, but don’t panic about it,” said Chiu. “This is something that needs to be further investigated and I really think that at this point we don’t know enough to recommend any changes to the standard public health measures that we use to prevent infections.”
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The team sequenced viral genomes from 2,172 nasal samples from COVID-19 patients in 44 counties in California from September 1, 2020 to January 29, although the sequencing focused on major metropolitan areas like Los Angeles, Alameda, San Francisco and counties of Santa Clara.
The team analyzed nasal swabs from more than 2,000 genomes to gather results.
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The variant, dubbed B.1.427 / B.1.429 or 20C / L452R, has increased to represent more than 50% of cases in multiple counties during the five-month sampling period. The study notes that the variant was detected in 459 of the 2,172 sampled genomes, or about 21%. The first reported case of the variant occurred in July in Los Angeles, although the sequence analysis suggests that it probably appeared in May 2020. This variant includes a single key mutation called L452R, not seen in other worrying variants, such as those identified for the first time in the United Kingdom, Brazil and South Africa, among other mutations.
“We were able to get some evidence that this is a more infectious variant,” said Chiu, noting a two-fold increase in patients’ virus concentrations in nasal smears. “This does not necessarily prove, but it does suggest, that it may be more infectious.”
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Another line of evidence behind the increase in transmissibility involved pseudoviruses that the researchers genetically modified to include the key L452R mutation.
“We found that these viruses were at least 40% more infectious than viruses that did not have this mutation,” continued Chiu. “The key mutation found in this variant appears, at least in vitro, in the laboratory, to be more infectious to cells.”
Public health experts say the same mitigation measures, such as wearing a mask, adequate spacing, hand hygiene and immediate and widespread vaccination, will help protect against variant strains of the virus.
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Three lines of evidence combine to form clinical, laboratory and other data that support claims that the variant could be more transmissible.
In addition, when the researchers examined 13 blood samples from recovered patients and vaccine recipients and tested how well the antibodies neutralized the variant compared to other strains, antibodies in the blood of two of the three recovered patients were four times less effective in neutralization of the variant, and antibodies to six of the eight vaccine recipients were twice as effective in neutralizing the variant.
Chiu said these vaccine recipients received two doses of the Pfizer or Moderna vaccines.
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Studies have suggested that the South African variant decreased the neutralizing power of the Pfizer vaccine by about two-thirds, while Moderna saw a six-fold reduction in neutralizing antibodies. Chiu notes that the California strain, by way of comparison, had a “moderate” effect.
The coronavirus variant lent a “moderate” reduction in the neutralizing power of recently approved vaccines, the study’s authors said.
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The retrospective analysis assessing virulence, or severe disease associated with the strain, was a difficult analysis, but the findings of 324 COVID-19 patients hospitalized in a tertiary hospital suggested a greater association with ICU stay and death. More specifically, the variant was detected in 69 patients. Chiu said 11% of hospitalized patients infected with the variant died, compared with 2% of hospitalized COVID-19 patients infected with a different strain. This difference is statistically significant, he said.
“As the number and proportion of severe cases were low in our cohort, resulting in wide confidence intervals, further investigation is needed to confirm these findings,” says the study. “Furthermore, as shown for B.1.1.7, it is difficult to discriminate whether the variant is inherently more virulent or whether the increased risk of serious illness is related to other factors, such as the resulting increase in transmissibility [in] a flow of cases that can deplete available health resources. “
“These data are still very preliminary, but they suggest that there may be a potential association between more serious diseases of the variant infection,” said Chiu.
There are still unanswered questions, such as the exact mechanism behind the L452R mutation. Although the mutation is located in the same region (the receptor-binding domain) as other mutations identified in global variants of interest, it does not come into direct contact with the ACE2 receptor, compared to the N501Y mutation in B.1.1.7 variant first detected in the UK, for example. Instead, the mutation approaches the ACE2 receptor, and separate initial data suggests that the mutation helps to stabilize the interaction between the spike protein and the ACE2 receptor.
Chiu said it is not clear at the moment whether the strain is responsible for a sharp increase in California virus cases. State data show that California experienced a large increase in cases from late December to mid-January, registering more than 40,000 infections daily. Chiu said the so-called “genetic drift” or the random appearance of “the right strain at the right time” may also be behind the increase. Another intriguing piece is the moment behind the sudden increase in the case in the state, when the variant probably appeared in the beginning of last spring. Researchers are still working to answer that question.
The key mutation L452R was also previously found in Denmark, but it was not the same variant, which hosts its own set of unique mutations.
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The California variant has not yet reached the level of a “VOC”, or concern variant, probably because of the unknowns associated with it so far, said the study’s author. This decision to coin the “VOC” strain should be left to public health officials and the Centers for Disease Control and Prevention, said Chiu.
Chiu said the researchers “urgently” need to accumulate more data to confirm the findings, especially the initial findings on infectivity, transmissibility and effect on neutralizing antibodies.