#16,866
As Omicron BA.5 continues to wrest control away from BA.2.12.1 in the United States (see CDC Nowcast: BA.5 Now > 50% of U.S. COVID Cases) and around the world, we continue to get new information on just how transmissible this latest generation of Omicron viruses really are.
Two weeks ago, in UKHSA Updated Risk Assessment As Omicron BA.4/BA.5 Become Dominant In The UK, we saw the latest UKHSA analysis suggesting that Omicron BA.5 is growing 35.1% faster than Omicron BA.2, while Omicron BA.4 is growing approximately 19.1% faster.
Much of this increased transmissibility is attributed to the virus's enhanced ability to evade immunity provided by vaccines or prior infection (or both), although there is little evidence to suggest that either produce any more severe illness than earlier Omicron variants.
Vaccination (and boosters) - along with prior infection - are still expected to reduce the severity of COVID illness, however.
We have seen hospitalizations increase in some countries where BA.5 has taken off, but it remains unclear whether that is due more to the sheer volume of infections rather than to any increase in disease severity.
Two days ago (July 5th) Nature published an early look at a new study on the enhanced antibody evasion of BA.2.12.1, BA.4, and BA.5. You'll find the link and a brief excerpt from the abstract below - followed by excerpts from a press release from Columbia University - but you'll want to read both in their entirety.
The upshot is, BA.4 and BA.5 are at least 4 times more resistant to prior immunity, giving them a huge advantage in transmissibility, while at the same time (further) limiting the treatment options with monoclonal antibodies.
Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, & BA.5
Qian Wang, Yicheng Guo, Sho Iketani, Manoj S. Nair, Zhiteng Li, Hiroshi Mohri, Maple Wang, Jian Yu, Anthony D. Bowen, Jennifer Y. Chang, Jayesh G. Shah, Nadia Nguyen, Zhiwei Chen, Kathrine Meyers, Michael T. Yin, Magdalena E. Sobieszczyk, Zizhang Sheng, Yaoxing Huang, Lihong Liu & David D. Ho
Nature (2022) Cite this article
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
Abstract
SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively1,2. These novel subvariants carrying additional mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals.
We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections.
Dominant omicron subvariants better at evading vaccines, antibody treatmentsPeer-Reviewed Publication
COLUMBIA UNIVERSITY IRVING MEDICAL CENTER
NEW YORK, NY (July 5, 2022)--The latest omicron subvariants—including the BA.4 and BA.5 forms causing new surges in infections in the United States—are even better at eluding vaccines and most antibody treatments than previous variants, finds a study by researchers at Columbia University Vagelos College of Physicians and Surgeons.
The study, led by David D. Ho, MD, director of the Aaron Diamond AIDS Research Center and the Clyde‘56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons, was published July 5 in Nature.
Subvariants BA.2.12.1, BA.4, and BA.5 are rapidly expanding worldwide, with BA.4/5 now making up more than 50% of new COVID cases in the United States. These subvariants are thought to be even more transmissible than prior omicron subvariants, owing to several new mutations in spike proteins.
"The virus is continuing to evolve, as expected, and it is not surprising that these new, more transmissible subvariants are becoming more dominant around the world,” says Ho. "Understanding how currently available vaccines and antibody treatments stand up to the new subvariants is critical to developing strategies to prevent severe disease, hospitalizations, and deaths—if not infection.”
In laboratory experiments, Ho and his team studied the ability of antibodies from individuals who received at least three doses of an mRNA vaccine, or got two shots and were then infected with omicron, to neutralize the new subvariants. (Ho’s team did not look at individuals who had not received a booster shot, because a previous study found that two doses provide little protection against infection by earlier omicron variants.)
The study revealed that while BA.2.12.1 is only modestly more resistant than BA.2 in individuals who were vaccinated and boosted, BA.4/5 was at least four times more resistant than its predecessor.
In addition, the scientists tested the ability of 19 monoclonal antibody treatments to neutralize the variants and found that only one of the available antibody treatments remained highly effective against both BA.2.12.1 and BA.4/5.
“Our study suggests that as these highly transmissible subvariants continue to expand around the globe, they will lead to more breakthrough infections in people who are vaccinated and boosted with currently available mRNA vaccines,” Ho says. Though the current study suggests that the new variants may cause more infections in vaccinated individuals, the vaccines continue to provide good protection against severe disease.
“Efforts in the United States to develop new vaccine boosters aimed at BA.4/5 may improve protection against infection and severe disease,” Ho says. “In the current environment, though, we may need to look toward developing new vaccines and treatments that can anticipate ongoing evolution of the SARS-CoV-2 virus.”
Due to its ability to continually reinvent itself, the future evolution and impact of COVID remains highly unpredictable. But, at least for the time being, our pandemic coronavirus appears in no hurry to retire gracefully.
