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9 big questions about Omicron explained
Why is the CDC changing its isolation guidance? Which type of test is best? And how long should you isolate or quarantine? Experts weigh in to help clear confusion.

BYEMILY SOHN
PUBLISHED JANUARY 6, 2022
• 10 MIN READ
As scientists learn what makes Omicron different from other versions of the SARS-CoV-2 virus, guidance about how to deal with the variant is changing fast. In the U.S., where Omicron is now the dominant variant, the Centers for Disease Control and Prevention have come under fire for their shifting guidelines, including a recently updated recommendation that halves the isolation period for people who test positive from 10 days to five.
What is the science behind the changing guidance, and how can people best protect themselves as Omicron spreads? Here’s what experts say you need to know.
Why did the CDC change its recommended isolation period?
The short answer? Practicality, says Gregory Poland, a vaccinologist and internal medicine specialist at the Mayo Clinic in Rochester, Minnesota. Because Omicron spreads so easily, cases have skyrocketed to more than 540,000 per day for the past seven days. And if hundreds of thousands of people all must isolate for 10 days, it becomes challenging to staff and operate critical businesses, including hospitals.
“What do you do if you have 20 percent or more of your healthcare workforce not able to work because they test positive?” says Poland. “You see a rapid rise in death and complications for whoever is in the hospital, because there are an inadequate number of healthcare workers.”
But there is also solid science behind the change. Studies have measured the concentration of live (and therefore contagious) virus in the noses of infected people and how levels change over time. They show that a person’s ability to transmit the virus typically peaks between a day or two before symptoms begin and two to three days after, says Jill Weatherhead, an infectious disease expert at the Baylor College of Medicine in Houston. So five days after a positive test, the amount of virus an infected person sheds drops sharply.

The new guidelines are a tradeoff, adds Abraar Karan, an infectious diseases doctor at Stanford University in Palo Alto. “The benefit is that we avoid huge losses in labor capacity,” he says. “The cost is that we send people back when they could still be infectious, although potentially far less so than earlier in their disease course.”
So five days after I test positive, I’m free?
Not exactly. The five-day recommendation only applies to people who are asymptomatic or whose symptoms are diminishing at that point.
A negative test around the five-day mark also doesn’t necessarily mean you’re in the clear, Karan says. “You could still be infectious, even if you test negative on an antigen test,” Karan says. “But you are likely less contagious than when your antigen was positive.”
People who are immunocompromised take longer to get rid of their infections, experts say, and should stay in isolation for up to 20 days. For people who have healthy immune systems and whose symptoms are declining, masking will reduce the risk of transmitting the virus after the fifth day. Even after five days of isolation, people should wear well-fitting, high-quality masks snugly over their mouths and noses.
“The idea with the updated guidance is that you're really covered during that peak time of contagiousness to protect from transmitting the virus,” Weatherhead says. “And in case you are a person that continues to shed virus after those five days, continuing to wear a mask will provide another layer of protection to prevent transmission.”
How do I count down the days in isolation?
To isolate properly and reduce risk, day zero begins when your first symptoms appear, even if you tested positive before symptoms started. Day one is the first full day after your symptoms begin. If you never get symptoms, day one is the first full day after your positive test.
Isolation only applies to people who have tested positive, according to the CDC. This means staying away from other people, even other household members, preferably in a “sick room” or area with its own bathroom.

If you find out you’ve been exposed to someone who tested positive, the CDC recommends that you quarantine. This also means staying away from others for a while, but the details depend on your vaccination status. If you have been boosted, if you have received your second Moderna shot within the last six months, your second Pfizer shot within the last five months, or if you have received the Johnson & Johnson vaccine within the last two months, you don’t need to quarantine, but you should wear a mask around other people for 10 days.
If you are unvaccinated or you are not within the recommended time windows for vaccines and boosters, the CDC recommends staying home for five days, then wearing a mask around other people for five more days. If you can’t quarantine, wear a mask for 10 days everywhere you go. Anyone who is a close contact of someone who tests positive should test on day five if possible. And if symptoms appear, get tested and stay home.
When will I stop testing positive?
The answer depends on which type of test you get, among other factors.
PCR tests detect genetic material from the SARS-CoV-2 virus. In some people, genetic remnants can linger in the nose for weeks or even months after the virus is no longer able to cause infections, Weatherhead says. Poland has a colleague who tested positive 16 weeks after their infection began.
Rapid antigen tests, on the other hand, detect viral proteins that are produced by live, active viruses. Those types of tests are unlikely to stay positive after levels of the virus are too low to cause infection.
A positive test of either kind doesn’t reveal how contagious you are, Weatherhead points out. Even though it may be tempting to interpret a faint line on a rapid test as a decline in infectiousness, faintness could simply be a result of how much virus you managed to pick up with the swab. “You're getting a ‘yes or no’ answer, not a ‘how much’ answer,” she says.

Do rapid tests even detect Omicron?
Available evidence suggests that yes, they do, Weatherhead says. Sensitivity might be slightly lower with the new variant, the FDA said in a statement in late December. Compared to PCR tests, rapid tests are less likely to detect infections in their earliest stages. But a U.K. Health Security Agency briefing analyzed the performance of rapid antigen tests at detecting Omicron, and it found no change in their performance with Omicron.
Will I start getting negative tests sooner if I’m vaccinated and boosted?
Theoretically yes, experts say. In a December 2021 study of people infected with several variants, including Delta and Alpha but not Omicron, researchers reported that vaccinated people with breakthrough cases cleared their infections in an average of 5.5 days. By contrast, unvaccinated people took 7.5 days to clear even though peak viral load was the same in both groups. Studies also show that fully vaccinated people are less likely to develop severe cases of COVID-19, including those who catch Omicron.
Vaccination “certainly reduces your risk of developing severe disease and requiring hospitalization, because the immune system [is] primed to reduce the viral burden,” Weatherhead says. “Whether that translates into how quickly you convert from a positive antigen test to a negative antigen test, I don't think we have that data yet.”
Do I need to have a negative test result to stop isolation?
Although many public health experts think it would be a good idea, the CDC is holding firm on its decision not to recommend a negative test before leaving isolation.
The best answer might depend on whether you are trying to make policy decisions or individual ones, Poland says. On a population level, it might make sense to require negative tests to prevent potentially infectious children from going to school, for example.

But in your personal life, Weatherhead says, what you choose to do depends on your own level of risk tolerance and the vulnerability of people around you. “If you're around people who are unvaccinated or who have underlying health conditions who are at high risk of disease, maybe it's better to take that test or wait the full 10 days beforehand,” she says.
If I test negative, do I still need to wear a mask?
If you're vaccinated, boosted, and healthy, you have dramatically lowered the chance that you will have severe disease, be hospitalized, or die, Poland says. But you have only moderately decreased the risk that you'll get infected with the Omicron variant. Given how transmissible the variant is, Poland recommends wearing a mask if you're gathering in an indoor setting with people not in your household.
Plenty of people can become infected without ever knowing it and pass the virus onward, Karan adds. Masking can slow transmission between people who may be infectious but are without symptoms.
Ultimately, people will need to consider their health conditions, risk tolerance, vaccination status, and COVID-19 levels in the community when making masking decisions, Weatherhead says. “In general, if everyone is fully vaccinated, asymptomatic and has a negative PCR test, the risk will be low and people do not universally need to wear a mask, particularly if gathering outdoors,” she says. People “who have underlying health conditions or are at high risk of progressing to severe disease if they become infected with SARS-CoV-2 may choose to continue to wear masks even around fully vaccinated groups.”
How will I know if I have Omicron?
Around the U.S., Omicron now accounts for more than 95 percent of new cases, according to data released this week by the CDC which uses a national surveillance system to get a sampling of circulating variants. But Delta is still around, and at-home tests won’t tell you which variant you have.

For all the variants, “the best thing we can do is really identify what our risk tolerances [are] and to make sure that we're protecting others, especially during that highly contagious period of time,” Weatherhead says. “Outside of that, making sure you're vaccinated, wearing your mask, will provide that layered approach to reduce those risks of transmission.”
 

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How booster shots can help protect you from Omicron
Immunity from COVID-19 vaccines fades over time, but data show boosters do offer better protection against all variants—including the more contagious Omicron.

BYSANJAY MISHRA
PUBLISHED DECEMBER 17, 2021
• 5 MIN READ
As the new Omicron variant spreads, experts say the best defense against all viral variants that cause COVID-19 is a full dose of a vaccine followed by a booster shot several months later.
Since the first mRNA vaccine against COVID-19 was authorized on December 11, 2020, studies have shown that unvaccinated people are at five times greater risk of getting infected and 10 times greater risk of hospitalization or death from COVID-19 than those who are fully vaccinated.
But research from Israel and the U.S. also revealed that vaccine-induced immunity against the SARS-CoV-2 coronavirus wanes in six to eight months. That’s especially worrying as more populations are exposed to the more contagious Omicron variant, which was first detected in November in South Africa.

Vaccine boosters provide
better protection against
the Omicron variant
Vaccine effectiveness
100%
80
Delta
75.5%
60
Omicron
40
34.2%
Vaccines are less effective against Omicron than Delta, but boosters almost restore vaccine effectiveness.
20
0
First
dose
2-9
10-14
15-19
20-24
25+
Booster
Weeks from second dose
Jason Treat, NGM Staff.
Source: Nick Andrews and others,
KHub.net 2021
To date Omicron has been reported in 77 countries. In the United States, the variant is in more than 37 states and makes up 3 percent of total cases; the rest are still Delta. But in London it now makes up the majority of positively diagnosed SARS-CoV-2 infections, and in South Africa it is the dominant strain.
Boosters, however, can restore antibody levels to their peak values—providing more robust protection against Omicron.
“Vaccines help to protect you, or at least prevent you from dying from the disease,” says Leo Poon, a virologist at the University of Hong Kong who detected some of the first cases of Omicron outside of South Africa. “And no matter what it is, Omicron or Delta, having a booster will be beneficial.”

What is a booster?
COVID-19 vaccines train our immune systems to make antibodies using synthetic versions of the virus’s spike protein—the part of the virus that helps it bind to human cells. If a vaccinated person later encounters the virus, the antibodies recognize it and bind to the spike protein to prevent infection.
The first dose of an mRNA vaccine prepares the cells to make antibodies, and the second dose matures and enhances those antibodies to bind even more strongly to the spike protein, so that it can’t anchor to receptors on human cells. In the case of the Johnson & Johnson vaccine, a single dose was enough to make sufficient antibodies against the original coronavirus.
But for all COVID-19 vaccines authorized to date, antibody levels do gradually decline, says Maria Elena Bottazzi, a vaccinologist at Texas Children’s Center for Vaccine Development at Baylor College of Medicine. That’s where boosters come in.
The booster dose is currently recommended by the U.S. Centers for Disease Control and Prevention for everyone ages 18 and older. The CDC says people should get boosted six months after their second dose of the Pfizer or Moderna mRNA vaccines, or two months after the J&J vaccine. The CDC has also recommended boosters for 16- and 17-year-olds who were fully vaccinated with two jabs of the Pfizer vaccine.
Scientists are still gathering evidence for how long immunity from the booster lasts and whether more will be needed down the line.
How does Omicron affect vaccines?
Since Omicron has accumulated over 30 mutations in the spike protein alone compared to the original virus, it seems to evade antibodies generated by two doses of the Pfizer or Moderna vaccines, or the single dose of the J&J vaccine, especially as antibody levels drop in the blood.
In a U.K. study that’s not yet been peer reviewed, the effectiveness of two shots of the Pfizer or AstraZeneca vaccines in preventing COVID-19 symptoms from Omicron fell to less than 40 percent within 15 weeks after the second dose. There was a lesser decline in the effectiveness of the Pfizer vaccine against Delta, but vaccine effectiveness still slipped to just 60 percent after 25 weeks.

Other preliminary studies from South Africa, Israel, and France also show steep declines in the ability of antibodies to neutralize Omicron in people vaccinated with the two-dose Pfizer vaccine or two doses of Moderna’s vaccine.
Boosters still work against Omicron
The good news is that a booster dose of the Pfizer vaccine increases antibody levels by 25-fold, which should be sufficient to neutralize Omicron. A booster dose of Moderna’s vaccine also improved the neutralization of Omicron compared to the previous two shots alone.
“The two doses with waning immunity mean there's no protection within a few months after the two doses,” says Peter Hotez, a pediatrician and vaccine scientist at Baylor College of Medicine. “The booster at least gives you something in the 70 percent range.”
Other studies show that when people received any mRNA booster dose, their antibody levels against Omicron rose to the protective level considered sufficient to prevent a COVID-19 infection.
“Our booster vaccine regimens work against Omicron,” Anthony Fauci said during a White House COVID-19 update on 15 December. “At this point, there is no need for a variant-specific booster,” Fauci added.
However, the data so far is largely from laboratory studies, and immunity involves more than just antibodies. More real-world data will be important to assess how effective current vaccines will be against Omicron in the long run.

 

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Omicron is dodging the immune system—but boosters show promising signs
Initial data on the new variant have experts worried about its ability to spread rapidly. But vaccine boosters still seem to be effective, as do some monoclonal antibody therapies.

BYSANJAY MISHRA
PUBLISHED DECEMBER 10, 2021
• 10 MIN READ
Two weeks after the world first learned about the Omicron variant, scientists now agree that it spreads faster than Delta, and it seems to evade existing immunity more easily than previous variants. But whether it causes more severe illness is still up for debate.
Despite multiple travel bans, the Omicron variant has already spread to 57 countries and has now been detected in 21 U.S. states. At least for now, though, Delta remains the most prevalent variant in the world and still causes most COVID-19 deaths globally.
Omicron was first detected in South Africa, and an ongoing analysis shows that it is the most contagious variant to date in that country. By the end of November—the most recent date for which data is available—Omicron accounted for 70 percent of all South African cases; it is projected to have risen to over 90 percent by now.
At the epicenter of the Omicron outbreak is South Africa’s Gauteng Province, where daily cases of COVID-19 are doubling about every three to four days. In the town of Tshwane, active COVID-19 cases have tripled from 6,697 to 20,425 within a week. And in Gauteng, the most populous province of South Africa, one in three tests are returning positive. This positivity rate means there is high transmission in the population, and the actual number of COVID-19 cases is likely to be even higher than the officially documented number.
A virus can spread faster because it might be more transmissible or because it can evade previous immune responses.
“Some of Omicron patients are shedding a lot of virus,” says Leo Poon, a virologist at the University of Hong Kong who detected some of the first cases of Omicron outside of South Africa. Poon’s study has shown that Omicron spreads very efficiently through air, “which may be causing higher transmission.”
But the evidence is converging that the “main advantage of Omicron [over Delta] comes from immune escape,” says Tom Wenseleers, an evolutionary biologist and biostatistician at the KU Leuven University in Belgium.

Why is Omicron different from past variants?
Multiplying viruses frequently mutate because of errors in replicating their own genetic material. So with each of the hundreds of thousands of new daily infections, the virus gets that many opportunities to mutate.
“Viruses are mutation-generating machines”, says Sergei Pond, a virologist at Temple University who has shown the trends in evolution of SARS-CoV-2 lineages.
New mutations in Omicron’s spike protein are a particular cause for concern. The spike is critical for SARS-CoV-2 to infect human cells and is the main target for antibodies. Mutations there can change the appearance of the spike and make it more difficult for antibodies to recognize and bind to it, enabling the virus to evade immunity.
Omicron has undergone over 50 mutations compared to the original virus, with over 30 mutations in its spike protein.
“When you put them all together, there's so many that there's the theoretical possibility that the shape of the spike protein will be overall substantially changed,” says Herbert “Skip” Virgin, an immunologist and chief scientific officer of Vir Biotechnology, Inc., which is developing COVID-19 therapeutics.
“We don't have any direct measurements of clinical impact of Omicron yet,” says Pond, but his preliminary analysis has identified significant changes in Omicron that are likely to influence both antibody neutralization and spike function.
Can Omicron reinfect those with natural immunity?
What has researchers most concerned is that Omicron can evade existing immunity, escaping antibodies generated through natural infection.
“Omicron, as opposed to Delta, appears to reinfect people who had previously been infected,” says Jerome Kim, head of the International Vaccine Institute in Seoul, South Korea. In South Africa, Omicron seems to be reinfecting about two and a half times more people than all previous variants.

“Reinfection risk has increased markedly since the beginning of October in South Africa, and this seems to correspond with the emergence of the Omicron variant,” says Juliet Pulliam, director of the South African DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis in Stellenbosch.
Analyses of antibodies in blood samples have estimated that 60 to 70 percent of people in South Africa had already been exposed to SARS-CoV-2 before Omicron was spotted. Pulliam’s study, which is not yet peer reviewed, scoured the PCR results of 2.5 million South Africans for evidence of reinfection. Her team found that about 10 percent of all infections in November occurred in people who had previously been positively diagnosed with COVID-19 since March 2020.
“This is what one would expect if Omicron is more resistant to neutralizing antibodies,” says Theodora Hatziioannou, a virologist at the Rockefeller University in New York City.
Are vaccines still effective against Omicron?
There are reports of post-vaccinated infections occurring with Omicron in Hong Kong, Minnesota, and Norway. In Denmark, where COVID-19 surveillance is very high, Omicron accounted for 3.1 percent of all cases in the past two weeks or so. That suggests the variant can spread even when more than 80 percent of the population is fully vaccinated.
“I was actually one of the first verified Omicron cases outside of Africa,” says Maor Elad, a cardiologist at Sheba Medical Center, Israel, who caught Omicron during a visit to London for a conference despite wearing masks and having received three doses of the Pfizer vaccine.
“I had symptoms for 48 hours: fever, muscle aches, sore throat, and then I was weak, fatigued, unwell for two or three additional days. But after five days, I recovered completely,” says Elad. Even if vaccinated, he adds, you can still get infected. “Vaccine efficiency is not 100 percent.”
However, it’s too early to assess whether current vaccines are not going to be effective against this new variant.

In the study by Poon in Hong Kong, Omicron patients had been fully vaccinated with Pfizer-BioNTech vaccine five to six months before they caught the variant. And from a preliminary report from Tshwane by the South African Medical Research Council, six of the 38 adults who contracted COVID-19 as of early December were vaccinated, 24 were unvaccinated, and eight had unknown vaccination status.
It’s also not yet clear whether vaccination status can explain the larger proportion of younger patients catching Omicron in South Africa. Only about 25 percent of people under 35 in that country has received a COVID-19 vaccine, and just 33 percent of the population in Gauteng is fully vaccinated against COVID-19.
In a press release, Pfizer says that three doses of its vaccine neutralize Omicron in lab studies, while two doses may be significantly less effective. This is in line with independent but still preliminary laboratory studies that suggest Pfizer’s vaccine is less effective against Omicron relative to the ancestral virus and previous variants.
But if the company’s data holds up, booster doses of the current vaccine should still provide some immunity. And multiple vaccine-makers are now racing to modify their vaccines for Omicron specifically.
Does Omicron cause more severe disease?
It’s still too early to assess the full impact of Omicron’s effect on disease severity because it takes about two weeks from infection to development of symptoms. However, even though hospitalizations are rising rapidly in South Africa, a report documenting the first two weeks of the Omicron wave shows that deaths—which tend to rise between two and eight weeks after the start of a new COVID-19 wave—in the biggest hospital in Gauteng have not echoed the dramatic rise in cases.
According to this early report, most patients didn’t show respiratory symptoms, most were admitted to the hospital for other medical reasons, and the length of hospital stays for COVID-positive patients was 2.8 days, compared to the average of 8.5 days during past 18 months.

That could be because “Omicron is still mainly circulating among younger people. Eighty percent of the hospitalized patients in Gauteng Province are under 50,” says Wenseleers, who has modeled earlier waves of the COVID-19 pandemic. Younger people typically endure milder infections than older people.
“Even now, we don't know whether Omicron could cause more severe clinical outcome or not,” says Poon. He led the team that sequenced the 2003 SARS coronavirus, established the earliest PCR test to diagnose SARS-CoV-2, and was on the international team of virologists that named the virus.
There is also no guarantee that Omicron’s impact in the U.S. and Europe—which have older populations—will be the same as in South Africa. But preliminary data as of December 8 showed that among all 337 Omicron cases detected in the European Union, symptoms were either mild or not present, and no deaths related to the new variant have been reported in member countries.
But even milder but more transmissible variants can be dangerous, according to Michael Ryan, Executive Director of the WHO Health Emergencies Program. If allowed to spread unchecked, the virus can infect greater numbers of people, who then overwhelm health systems, causing a spike in deaths. Worryingly, an analysis from the U.K. Health Security Agency suggests that the window between infection and infectiousness may be shorter for Omicron than for the Delta variant.
Will current therapies still work?
Four monoclonal antibody products are currently authorized to treat mild to moderate COVID-19 in non-hospitalized patients who are at high risk for progressing to severe disease or hospitalization.
In a study not yet peer reviewed, a monoclonal from GSK and Vir Biotechnology called Sotrovimab remained effective against a lab-made Omicron-like virus. “Sotrovimab is capable of neutralizing the Omicron variant, including all 37 of the mutations, [which makes us] very optimistic that Omicron can be dealt with therapeutically,” says Vir Biotechnology’s Virgin.

“Despite the considerable evolution of the virus with Omicron, we have evidence that effective therapeutics are available to control the pandemic,” says Davide Corti, a leading antibody researcher at Vir Biotechnology. That’s critical if Omicron causes a high percentage of cases in people who are vaccinated. Whether other therapeutic antibodies can block Omicron is currently unknown, but Virgin remains optimistic about available treatments.
“The vaccines are a remarkable accomplishment, even if they lose activity against a certain variant,” he says. “People should get vaccinated, and should they begin to develop symptoms that might be due to coronavirus, they should immediately seek medical attention, because it's not hopeless."

 
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