Experts warned that regions with low vaccination rates could allow the virus that causes COVID-19 to evolve more rapidly, possibly yielding a more transmissible or antibody-resistant variant that would escalate the pandemic. Now this prediction may have come true.
Last week the World Health Organization named a new SARS-CoV-2 variant Omicron and classified it as a variant of concern, along with Alpha, Beta, Gamma, and Delta. The variant was discovered in South Africa, where just 23 percent of the population is vaccinated, due in part to most supplies going to North America and Europe. However, at this early stage there is still a lot scientists can’t say for sure about Omicron and its potential to worsen the COVID-19 pandemic. So far most breakthrough cases involving this variant seem to be mild, and it’s unclear how much the mutations will erode vaccine efficacy. It is also unknown whether Omicron will cause more severe illness than Delta.
Preliminary evidence from South Africa suggests that Omicron might be more transmissible than previous variants: Positive cases in the Tshwane region of Gauteng Province—where Omicron was first detected on November 9—increased from less than one percent to more than 30 percent of collected samples in the past three weeks. Omicron now makes up 76 percent of all SARS-CoV-2 sequenced in South Africa, making it the most prevalent variant in the country. It is replacing other variants faster than Delta replaced Beta.
“[It is] a reminder we have this new variant as a result of failure to control infections,” says Ravi Gupta, a clinical microbiologist at the University of Cambridge who is one of the world’s leading researchers on COVID-19.
Omicron shares many key mutations with previous variants of concern, but it has also accumulated a dozen novel mutations on its spike protein, the part of the virus that is essential for infecting human cells. The new variant has 32 mutations in this region overall, and scientists fear the large number might diminish the ability of existing antibodies to neutralize the variant, making current vaccines less effective.
“It has mutations at virtually every site that current antibodies would bind to,” says Michael Worobey, who studies the evolution of viruses at the University of Arizona. There are also mutations that could make Omicron infect cells faster and transmit from person to person more easily. “This one is worrying, and I’ve not said that since Delta,” says Gupta.
“While we know there are many mutations, in the case of this [Omicron] variant, we don’t yet know what their overall effect is,” cautions Kei Sato, a virologist at the University of Tokyo. Only about 1,000 people have been diagnosed with Omicron, and scientists currently have very few samples and genetic sequences from South Africa, which makes it difficult for experts to draw firm conclusions about Omicron’s contagiousness and whether it causes more severe disease.
On the bright side, antibodies taken from people who were first naturally infected and then vaccinated were still able to neutralize a synthetic Omicron-type virus in the laboratory. That suggests a booster dose of an mRNA vaccine may still provide robust protection against Omicron.
Omicron “is a cause for concern, not a cause for panic,” U.S. President Joe Biden said in a press briefing on Monday morning. “The best protection against this new variant or any of the various out there, the ones we’ve been dealing with already, is getting fully vaccinated and getting a booster shot.”
For now, “we have every indication that the vaccines are still effective in preventing severe disease and or complications,” says Ian Sanne, an infectious diseases specialist at University of Witwatersrand in Johannesburg, South Africa. “The data, however, is small and early.”
Omicron’s worrisome mutations
When an individual encounters the SARS-CoV-2 virus, the body’s immune cells produce antibodies that target the spike protein, the part the virus uses to attach to the ACE2 receptor protein on human cells and infect them. When antibodies bind to the spike, the virus is blocked from entering the cell. Because the spike is essential for infection, all currently authorized vaccines use it to train the body’s immune response.
The 32 mutations that occur in Omicron’s spike gene can be organized into three groups, depending on how they alter the function of the spike protein, says Olivier Schwartz, a virologist and immunologist at the Pasteur Institute in France.
Some mutations enhance the spike protein’s ability to bind to the human ACE2 receptor; some help the surface of the virus fuse with the cell and allow the virus to enter; others alter the appearance of the spike protein, making it harder to recognize and allowing the virus to evade antibodies.
Of the many mutations on Omicron’s spike, the loss of amino acids at positions 69 and 70 makes the virus twice as infectious as the original virus. But in a stroke of luck, these two mutations are not present in Delta, making Omicron easy to distinguish in a widely used PCR assay.
The University of Cambridge’s Gupta has previously shown that these deleted amino acids, along with a third mutation at position 796 on the spike protein, are associated with Alpha’s ability to evade the body’s immune response. This suggests these same three mutations could help Omicron escape existing immunity either from vaccines or previous infections—and some preliminary evidence suggests that is happening.
“To date there have been a number of breakthrough infections, but they have been mild,” says Barry Schoub, a virologist and adviser on COVID-19 vaccines to South Africa's government. However, experts say it is too early to know whether Omicron causes more severe disease as there is a lag between infection and hospitalization.
Another cluster of mutations in Omicron at positions 655, 679 and 681 of the spike protein are thought to help the virus infect human cells more easily; they also exist in the Mu variant and are known to enhance its transmissibility.
Additionally, in a study not yet peer reviewed, researchers suggest that a mutation that Omicron shares with Alpha and Mu might help it replicate faster and resist immunity. And a mutation at the 501 position also found in Alpha, Beta, and Gamma makes the spike protein attach more tightly to the ACE2 receptor, making the virus more efficient at infecting cells.
“We see this virus spreading pretty rapidly in a population with, we think, very high levels of immunity,“ says Richard Lessells, infectious diseases specialist at the University of KwaZulu-Natal in Durban, South Africa. “That's what gives us concern,” he adds. “[Omicron] could have kind of more immune evasion than previous variants.”
In the Gauteng region of South Africa, blood samples suggest 80 percent of the population already had some immunity because of encounters with previous SARS-CoV-2 variants. That’s why experts are worried about the rapid rise of Omicron, which accounted for 76 percent of cases in just a couple of weeks. By comparison, it took Delta several months to reach that level of prevalence.
The number of COVID-19 hospitalizations in South Africa has also risen sharply within the last month, but whether that is due to overall numbers of people becoming infected or due to specific infection with Omicron is not yet clear.
“There's not enough information available yet to make a conclusion about the severity of Omicron in comparison to other variants,” says Ben Cowling, an epidemiologist at the University of Hong Kong. That’s because most early cases are among university students and younger people, who generally develop more mild disease.
With current data, it’s also not clear whether the growth advantage of Omicron over Delta is because of its ability to escape immunity by reinfecting previously immune people, or by infecting individuals who haven’t been exposed to the virus, notes Tom Wenseleers, an evolutionary biologist and biostatistician at the KU Leuven University in Belgium.
While the number of people testing positive in areas of South Africa affected by Omicron has risen sharply, there is not enough data to conclude whether that is entirely due to Omicron or to superspreader events among students and young people.
Despite the worrying rise in cases, preliminary data, including studies from Theodora Hatziioannou’s lab in New York, suggest that vaccines and boosters are still powerful tools against the virus.
Researchers led by Hatziioannou, of the Rockefeller University in New York, created a synthetic version of the virus that contained many of the spike protein mutations that Omicron carries. They found that neutralizing antibodies from people who had recovered from COVID-19 and then got an mRNA vaccine dose were able to fend off the mutated synthetic virus.
However, it takes between two and three weeks after infection for COVID-19 to develop and the severity of the disease to be gauged, explains Sanne, which means it will take time to determine whether the existing vaccines hold up against Omicron in the real world.
In the meantime, the best way to avoid any type of infection from Omicron or any other variant is to get more people vaccinated and for governments to continue promoting public health measures such as social distancing and mask wearing. “Please get vaccinated and boosted and mask up in public, as the mutations in this virus likely result in high-level escape from neutralizing antibodies,” says Gupta.
“The primary way to minimize the emergence of new variants is to limit ongoing transmissions,” adds Ridhwaan Suliman, a senior researcher at the Council for Scientific and Industrial Research in South Africa. “Viruses can't mutate if they can't replicate.”