Q&A on the Omicron Variant

Also on Dec. 2, confirmed omicron cases were identified in New York, Colorado and Hawaii. The Colorado case is a woman who recently traveled to multiple countries in southern Africa, was fully vaccinated and had mild symptoms. She had not yet received a booster dose of the COVID-19 vaccines, the Colorado Department of Public Health and Environment said, and her close contacts have tested negative.

The New York and Hawaii cases indicate the variant has spread in the U.S. outside of people traveling from Africa. Five cases were identified in New York, one on Long Island and four in the New York City area. “This is not just due to people who are traveling to southern Africa or to other parts of the world where omicron has already been identified,” New York City Health Commissioner Dr. Dave Chokshi said. One person among those five is vaccinated, and the vaccination status of the others is unknown.

The case in Hawaii was an unvaccinated person who had previously been infected with SARS-CoV-2, the state Department of Health said. “This is a case of community spread. The individual has no history of travel,” a press release said.

On Dec. 3, Nebraska health officials announced six confirmed omicron cases, likely linked to one person’s recent travel to Nigeria. Only one of the six people was vaccinated.

How contagious is the omicron variant?

It’s not known yet whether the omicron variant spreads more easily than the highly transmissible delta variant, but many scientists suspect that it may. Several of the mutations present in the omicron genome, including some at the virus’s furin cleavage site, have been linked to increased transmissibility. That site is a spot on the virus’s spike protein that’s cut by the enzyme furin to activate the spike and prepare the virus for entering cells.

One pair of key mutations has also been shown in lab tests to allow SARS-CoV-2 viruses to bind more strongly to the ACE2, the human receptor that the virus uses to gain entry into cells. At the same time, other mutations are thought to reduce the affinity for ACE2.

Analysis of the mutations, according to the Centers for Disease Control and Prevention, suggests omicron is “likely to have increased transmission compared to the original SARS-CoV-2 virus, but it is difficult to infer if it is more transmissible than Delta.”

The current surge of COVID-19 cases in South Africa, which appears to be primarily due to omicron, also suggests the variant could be more contagious. Interpreting the preliminary epidemiological data, however, can be tricky, so it’s still too premature to come to firm conclusions.

It’s possible, for example, that the uptick in cases happened by chance and was sparked by a superspreading event in a person or people who happened to be infected with omicron, rather than because of a change in the virus’s intrinsic transmissibility.

Alternatively, as University of Bern computational epidemiologist Christian Althaus noted on Twitter, the surge in cases might also be explained if the variant can evade immunity from prior infection or vaccination — or it could be some combination of immune evasion and a bump up in contagiousness.

Prior to the latest rise in cases, South Africa had relatively little coronavirus transmission, also making it difficult to say whether omicron can necessarily outcompete delta, either because of increased transmissibility or immune evasion.

Watching what omicron does in other places will provide a clue as to what’s going on, Althaus said in a Nov. 30 conversation hosted by the Swiss National Science Foundation. Highly transmissible delta spread very quickly in most countries, he said, but a virus with an ability to circumvent a trained immune system could behave differently in countries with different levels of vaccination or previous infection. “I expect that if omicron spreads worldwide, it could spread at quite a different pace in different countries,” Althaus said.

How well does previous infection or vaccination protect against omicron?

One of the most concerning aspects of omicron is its potential to evade immunity gained either from vaccination or previous infection. Omicron contains numerous mutations in its spike gene that are predicted to make neutralizing antibodies less effective, suggesting the variant could have an easier time reinfecting people who have recovered from COVID-19 and infecting vaccinated people.

Preliminary epidemiology data from South Africa also suggest that omicron is reinfecting people more frequently than would be expected if it did not have any new ability to get around prior immunity. Researchers there posted an unpublished study to the preprint server medRxiv on Dec. 2 that concluded that, unlike with the beta and delta variants, there is “population-level evidence” that omicron “is associated with substantial ability to evade immunity from prior infection.”

Immunologists, however, do not think all is lost. “I expect a substantial drop in protection against overall infections and mild disease, but less of a drop against severe disease,” Deepta Bhattacharya, an immunologist at the University of Arizona College of Medicine, told us.

Neutralizing antibodies, which prevent cells from becoming infected with the virus, are likely to be far less effective against omicron, he said, but they’re not the only defense. Other parts of the immune system, such as T cells, he said, “should be much less affected.”

In a couple of weeks, it should become more clear how impotent people’s neutralizing antibodies are against the variant. In the lab, scientists will test whether and at what concentration sera from vaccinated people and from convalescent patients can neutralize omicron or a mock virus with a similar set of mutations.

Even if those results end up sounding pretty bad — say, a 50-fold drop in neutralization against omicron compared with delta or alpha — antibodies may still afford a fair amount of protection, depending on their starting levels, Washington University School of Medicine in St. Louis virologist Larissa Thackray told STAT News. A 100-fold drop or more, though, would likely mean the antibodies aren’t doing much, although someone would still have T cells to fall back on.

As Bhattacharya told us, “neither people who have been vaccinated nor those who recovered from COVID in the past will be back to square one—the immune system has too many backup paths and failsafe mechanisms.”

It’s also too early to know whether vaccinated people or those who have been previously infected would fare better against omicron. Wherry, the University of Pennsylvania immunologist, said that for the other variants, both are protective, but vaccination immunity is “typically more consistent at the antibody level,” while “there may be broader T cell responses after infection.”

There is some evidence to suggest that people who have had COVID-19 and also have been vaccinated might do better. In a paper published in September in the journal Nature, Paul Bieniasz’s lab at Rockefeller University found that antibodies from people fully vaccinated with an mRNA vaccine or from those who had contracted COVID-19 previously were almost entirely incapable of neutralizing a virus with 20 spike mutations, many of which are shared with omicron.

“What was interesting is that antibodies from people who had recovered from infection and then gotten vaccinated later actually did fine,” Bhattacharya said in an email. “So the real question is whether people who have received a 3rd vaccine dose will also be fine. I suspect they will be based on studies done on beta, but we will see soon.”

What have vaccine manufacturers said about the need and timeline for omicron-specific vaccines?

Vaccine manufacturers have offered mixed predictions of how the vaccines will perform against omicron, but said in late November that it would be a few weeks before they’ll have results from lab tests. It will take longer to gather data on the real-world experience of vaccinated people.

Stéphane Bancel, CEO of Moderna, told the Financial Times that he thinks there will be “a material drop” in effectiveness, but “we need to wait for the data.” The scientists Bancel has spoken to are saying, “‘This is not going to be good,’” the CEO told the newspaper for a Nov. 30 story.

Paul Burton, chief medical officer of Moderna, told BBC News that if a new vaccine is required against the variant, it would be sometime in early in 2022 when that would be available “in large quantities.”

Ugur Sahin, co-founder of BioNTech, told the Wall Street Journal that the T cells will likely be able to destroy the omicron variant, even if antibodies have difficulty neutralizing the variant. That would mean the vaccines would still help prevent severe disease. “Our message is: Don’t freak out, the plan remains the same: Speed up the administration of a third booster shot,” Sahin said on Nov. 30.

Pfizer/BioNTech said if it needed to manufacture a new vaccine, it would take about 100 days to start shipping it.

Johnson & Johnson was also upbeat about the ability of its current vaccine to combat omicron but, like the other manufacturers, said it had begun gathering data on omicron and developing a new vaccine against the variant in case it was needed.

“We remain confident in the robust humoral and cell-mediated immune responses elicited by the Johnson & Johnson COVID-19 vaccine demonstrated by the durability and breadth of protection against variants to date in clinical studies,” said Dr. Mathai Mammen, global head of Janssen Research & Development LLC, Johnson & Johnson, in a press release.

Is omicron more dangerous than past versions of the virus?

It is still too early to tell if the omicron variant is more or less virulent than the now-dominant delta variant.

Some anecdotal reports from physicians in South Africa have indicated that perhaps omicron could be less pathogenic than other variants, as many of the illnesses appear to be mild or without symptoms. At the same time, preliminary data from the country point to an increase in the number of hospitalizations.

Experts say the limited data are hard to parse, and there are several factors other than a change in disease severity that could explain the observations. For example, the uptick in hospitalizations could just be a result of more people becoming infected, as the World Health Organization has explained.

And the large number of mild cases might just reflect who is getting infected. So far, many of the initial infections in South Africa have been in college students, who typically don’t get very ill. Travelers, too, may be more likely to be in good health.

Another factor complicating any evaluation of disease severity: immunity in the population, either from previous infection or vaccines. Previous exposure could make the infection appear less dangerous than it is, masking an increase in virulence.

“This is very new,” said Dr. Volker Thiel, a virologist at the University of Bern, in the conversation hosted by the Swiss National Science Foundation. He noted that the majority of people haven’t been infected for more than a week or two, and so wouldn’t be expected to be in the hospital yet anyway. “We really can’t say anything about severity of disease at the moment,” he said.

A Dec. 2 threat assessment brief from the European Centre for Disease Prevention and Control similarly explains that while none of the few omicron cases so far in Europe have been severe, it would take hundreds of cases to observe patients with complications if the severity is similar to the delta variant — and it could be a little while before this becomes more clear. “Severity outcomes often take several weeks to accumulate and longer to be evident at population level, impacting hospital rates,” it reads.

Can the omicron variant still be detected with existing diagnostic tests?

So far, it appears that the omicron variant can be detected with existing COVID-19 diagnostics. This includes highly sensitive polymerase chain reaction, or PCR, tests, which evaluate the presence of viral RNA in a sample, along with rapid tests that check for viral proteins, or antigens.

In a Nov. 30 statement, the Food and Drug Administration said that on “preliminary review,” the agency believes both types of tests “show low likelihood of being impacted and continue to work,” although it would continue to monitor the situation.

The omicron variant does perform differently than most other variants on a part of a PCR test, which may help identify it more rapidly. Due to a deletion in the S, or spike, gene, omicron variant samples will not test positive for that particular part of the virus, producing what scientists are referring to as “S gene dropout.” Simultaneous checks for two other parts of the virus still work, though.

“You still get a positive test, but you don’t see the S gene because a mutation means that part of the test doesn’t work,” explained Emma Hodcroft, a postdoctoral researcher at the University of Bern and a co-developer of the virus-tracking site Nextstrain, in the conversation hosted by the Swiss National Science Foundation.

Scientists have seen this before, particularly with the alpha variant, when S gene dropout was used as a rough proxy for the variant. This feature may help countries focus their surveillance efforts and could serve as an early sign of omicron circulating in populations more widely.

Hodcroft, however, cautioned that the test result is not foolproof, since S gene dropout is observed in other variants. “We’ve seen it pop up independently all over the phylogeny, including in delta,” she said. “So just seeing the S gene dropout doesn’t mean you’re seeing omicron.” For this reason, she said it’s important for people to sequence the viruses that do show S gene dropout to confirm that it is omicron.

Do treatments still work against infections with the omicron variant?

Based on what is known about omicron now, a few treatments are expected to work less well against omicron, particularly some of the monoclonal antibodies that target the SARS-CoV-2 virus.

Mutations present in the variant are predicted to dramatically reduce the ability of certain synthetic antibodies to bind the virus, although experimental tests are needed to confirm this. 

The FDA has said it is evaluating the potential effect of omicron on therapeutics and will update the public once it knows more. The agency has limited the use of certain monoclonal antibodies based on variants before.

Other treatments, such as those that target the immune response, including steroids, will be unaffected.

Gilead, the maker of the antiviral drug remdesivir, which works by inhibiting viral replication via the viral polymerase, said in a Dec. 1 statement that analysis of omicron sequences does not show any new mutations in the polymerase, so it expects the drug to be active against the variant. The company is working to confirm this with lab tests.

What can I do to protect myself from omicron?

The CDC recommends following the same public health advice as for other variants of the coronavirus. That includes wearing a mask when indoors in areas with substantial or high transmission, washing your hands frequently, physically distancing from others, and most importantly, getting fully vaccinated if you are 5 years of age or older.

Even though it’s not known exactly how effective vaccination will be against omicron, it almost certainly will provide some protection, and of course will help against delta, which is still the dominant variant in the U.S.

“The vaccines are so efficient and they work so great, there is so far no indication that they would not at least partially protect you against this new variant,” said the University of Bern’s Thiel. “And even if it’s only a partial protection, it may make the difference between severe or mild disease or between severe disease and death.”

In light of omicron, the CDC also changed its stance on boosters on Nov. 29, and now recommends that all adults, not just those who are older or higher risk, receive an additional shot.

Several immunologists we contacted agreed with this advice. “[W]e have seen that boosting (and the original vaccination) induce antibodies and memory B cells that are capable of efficient recognition of variants not included in the vaccine,” Wherry said in an email. 

“Even if boosted antibodies have some reduction in efficacy against omicron, the substantially higher antibodies levels generated after the boost are expected to perhaps offset slightly lower neutralization capacity.” But, he acknowledged, whether that will be true isn’t yet known.

Bhattacharya said the closest test case for whether a booster would help with omicron is with the beta variant, which shares some similarity with the newer variant. A third dose of the Moderna vaccine did just as well as one matched to beta, he noted, at least as measured by the neutralizing antibodies produced.

“Omicron has a few more mutations than beta at key places, so it could be that the 3rd (unmatched) dose will do a bit worse than it did against Beta. But the reality is that there won’t be an Omicron-matched shot  available for months” he said in an email. “We know that a 3rd dose does great against Delta, which by far is still the immediate threat, and I very much suspect it will help a lot against Omicron too should it start to spread widely.”

Other experts, however, disagree with the government’s booster recommendations. Dr. Paul A. Offit, a pediatrician and vaccine expert at the Children’s Hospital of Philadelphia, fully supports primary vaccination and boosters for select individuals, but doesn’t think additional shots are necessary yet for the broader, healthy population.

“It looks like although this virus may be more contagious, there’s no evidence that it’s more virulent and nor is there any evidence that it reduces vaccine-induced protection against severe disease,” he said about omicron in a phone interview, adding that this has been true for three other variants already.

“The only possible explanation you can argue for boosting is that it will boost your antibody level up to the point that you are better protected against mild illness in the short term,” he said, adding that that would fade, regardless of the number of additional doses. “We’re holding this vaccine to a standard to which we hold no vaccine.”

The World Health Organization does not support boosters for all adults, even to combat omicron.

“Right now, there is no evidence that I’m aware of that would suggest that boosting the entire population is going to necessarily provide any greater protection for otherwise healthy individuals against hospitalization or death,” said Dr. Mike Ryan, executive director of WHO’s health emergencies programme, on Dec. 1. “The real risk of severe disease, hospitalization and death lies in particularly at-risk and vulnerable individuals who do require protection against all variants of COVID-19.”

Indeed, for all the attention omicron has received, multiple experts said it would be foolish to forget about virtually all of the infections in the U.S. that are due to delta.

“We will learn the answers over the next few weeks,” Wherry said of omicron. “However, infections in the US are going up dramatically from delta. We are not out of the woods yet. Best things we can do – get people vaccinated and boosted, mask, still social distance where appropriate, avoid crowded indoor activities. … And trust the science.”

What travel restrictions did the U.S. implement?

On Nov. 26, the White House announced it wouldn’t allow most noncitizens coming from eight African countries to enter the United States, effective at 12:01 a.m. Nov. 29.

The presidential proclamation said that noncitizens who were in Botswana, Eswatini, Lesotho, Malawi, Mozambique, Namibia, South Africa and Zimbabwe in the 14 prior days cannot enter the U.S. However, the travel suspension doesn’t apply to U.S. citizens or lawful permanent residents and nationals (meaning residents of U.S. territories), and some close family members of U.S. citizens or lawful permanent residents.

Noncitizen family members who are exempted from the policy include spouses; parents or legal guardians of those unmarried and under age 21; siblings if both are unmarried and under 21; children, foster children, wards and prospective adoptees. Also exempt are noncitizens invited to the U.S. to help contain or mitigate the coronavirus; noncitizen air and sea crewmembers; noncitizen members of the U.S. military and their spouses and children; certain visa holders such as foreign government officials; and others who would be needed for law enforcement or national interest objectives.

Several other countries also have implemented travel restrictions on southern Africa nations, with some suspending all flights. Israel closed its borders on Nov. 29, allowing only citizens to enter and requiring them to quarantine and test. Japan also barred all foreign travelers on Nov. 30.

The African nations targeted by these restrictions have low rates of vaccination against COVID-19. While 58.2% of the U.S. population is fully vaccinated, and many are getting booster shots, vaccination rates ranged from 26.5% in Lesotho to 3.1% in Malawi, according to statistics gathered by Our World in Data. In South Africa, 24.1% of the population is fully vaccinated.

What impact are those restrictions likely to have?

Past studies on international travel restrictions have shown they can slow the spread of diseases, if they are strict enough. But such restrictions don’t contain diseases. Biden has said the point of the travel limitation is “to give us time to get people to get protection, to be vaccinated and get the booster.” He said in remarks on Nov. 29, “We needed time to give people an opportunity to say, ‘Get that vaccination now’ before it — it’s going to move around the world.”

But the variant had already started to “move around the world” — with cases detected in several European countries, as well as Israel, Canada, Australia and Hong Kong, before the U.S. travel restrictions were implemented. In a Nov. 27 interview with NBC News’ “Weekend Today,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said he “would not be surprised” if the variant had already arrived to the U.S., adding that the travel restrictions could “give us time to assess it better.”

And, in fact, omicron had already arrived. The CDC confirmed the first known case in the U.S. on Dec. 1, and a handful of other cases in the country were announced the following day.

When we wrote about travel restrictions on China in 2020, Saad B. Omer, director of the Yale Institute for Global Health, told us such restrictions implemented to halt the spread of a virus “can have an impact if you shut down 90% of all travel.” But, “even then, it delays it a little bit but it doesn’t stop it.”

As with the restrictions on China, the latest travel limitations have exceptions and don’t pertain to every country in which the virus — or in this case, variant — has been detected. Omer told NPR of the restrictions related to omicron: “If the question is to prevent the variant from coming in, it really doesn’t make sense to exempt countries where it has been identified and that has even more direct flights than southern Africa.”

One study, published in Science in 2020, looked at both the travel restrictions and other emergency measures put in place early in the coronavirus pandemic in China, and estimated that shutting down Wuhan, China, slowed the virus’ spread to other cities in the country by 2.91 days.

Similarly, other studies have found modest effects. A 2014 review of 23 studies on the impact of travel restrictions on the spread of influenza published in the Bulletin of the World Health Organization found overall they have “only limited effectiveness,” the degree of which varied depending on the restrictions themselves, epidemic size, transmissibility of the virus and other geographic considerations. 

South African epidemiologist Salim Abdool Karim told CNN that south African countries were being “punished” for “having good surveillance” and “being transparent.”

Karim, a former co-chair of South Africa’s Ministerial Advisory Committee on COVID-19, said in a Nov. 29 interview that the travel limits put in place by many countries will be “superfluous and irrelevant.” The first confirmed specimen of omicron was collected on Nov. 9 in South Africa. “Transmission has probably seeded itself in most countries,” he said. Blocking travel is “probably just going to slow the seeding slightly at best but it will probably have little if any impact.”

Unlike with the travel restrictions on China, this time the U.S. has another tool to limit the spread of the virus: testing requirements for anyone, including U.S. citizens, age 2 and older flying into the country. Everyone flying into the U.S. must get a viral test with a negative result within one day of their flight to the U.S. The Biden administration tightened this requirement effective next week; fully vaccinated individuals previously could get their negative test results within three days of their flight.

As we’ve explained before, testing can help limit the spread, but it’s still possible for someone to test negative early in the course of an infection, before the amount of virus is sufficient to be detected — particularly when using the popular rapid tests that are less sensitive than a PCR test, which can take a few days to get results.

How did omicron come about?

It’s still uncertain how omicron evolved, but it’s clear that the variant did not descend from delta or other known variants of SARS-CoV-2. In fact, sequencing data suggests the viral lineage goes way back, possibly to mid-2020. Omicron itself, however, is much newer, as current estimates indicate it began circulating in people only around mid-October.

Based on this information, scientists have put forward three main hypotheses for how omicron originated. The first is that the variant simply has been spreading under the radar in a population that isn’t regularly sequencing viral samples, perhaps somewhere in southern Africa.

Or, the variant may have evolved in one or more immunocompromised people, such as a person with HIV. In this scenario, a weakened immune system would allow the virus to continue to replicate for a prolonged time in a person’s body, racking up mutations over time. This mechanism has been hypothesized for the creation of previous variants, and viruses isolated from such patients have been shown to accumulate mutations, including those often seen in variants of concern.

Finally, it’s possible that the virus made its way into animals in what’s called a reverse zoonosis and then was transmitted back to a person. That would explain how the highly mutated variant came about without anyone noticing. And as Kristian Andersen, an infectious diseases and genomics expert at Scripps Research, has pointed out on Twitter, some of the mutations in omicron have been seen in animals, such as rodents.

While he slightly favors the latter hypothesis, Andersen acknowledges there’s little hard data to go on and all of the origin stories are possible.

Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.