What Doctors Need to Know About Omicron

 Public health and infectious disease experts warn that there's still much to be learned about the new SARS-CoV-2 variant, Omicron (or B.1.1.529), but here's what we do know so far, broken down by key questions.

The new variant was first detected in Botswana on November 11, and then identified in South Africa 3 days later. It was also detected on November 13 in Hong Kong in a national returning from South Africa.

The World Health Organization (WHO) labeled it a "variant of concern" last Friday.

A total of 168 samples of the variant from 11 countries have been uploaded to GISAID as of 3 p.m. ET on Monday.

Is Omicron More Transmissible?

It's not yet clear whether Omicron is more transmissible than previous versions of SARS-CoV-2, but South African health officials have noted that the rapid increase in cases in Gauteng province is concerning.

During a press briefing last week, Tulio de Oliveira, PhD, director of the Centre for Epidemic Response & Innovation in South Africa, said that test positivity rates in the Tshwane region (which is in Gauteng province) jumped from 1% to over 30% in the last 3 weeks alone, and almost all recent samples from the province have been the Omicron variant.

Experts cautioned that the spike could be due to the "founder effect," wherein a single case in an area of low prevalence is responsible for thousands of cases there. It's not yet clear whether that's what happened in South Africa, and a better answer is expected in the next few weeks.

Does Omicron Cause More Severe Disease?

There's no evidence yet that Omicron causes more severe disease, but again, researchers will have a clearer picture in a few weeks.

There was some excitement late last week when a South African physician who'd first raised the alarm over the new strain said most cases she'd treated were "extremely mild." Angelique Coetzee, MD, chair of the South African Medical Association, told the BBC that the symptoms were "unusual" and differed from the Delta variant, focusing on fatigue and body aches.

Yet this small sample may only include younger patients who may be less likely to suffer severe disease from infection, experts warned. More data need to be gathered before drawing any conclusions about severity.

Can Omicron Evade Immunity?

The WHO said it has preliminary evidence of increased re-infection risk with Omicron, but the agency has not shared the supporting data, noted Jeremy Faust, MD, of Brigham and Women's Hospital in Boston, in his newsletter, Inside Medicine.

When it comes to vaccinated immunity, Faust said that it's "possible, and perhaps even likely, that Omicron partially lowers our vaccines' effectiveness against infection."

That's because it has 32 mutations in the spike protein alone, some of which were associated with immune escape for previous variants.

Still, Faust added that it's possible that vaccines will hold up against severe disease in the face of this new variant.

What Mutations Are Concerning?

Omicron has multiple mutations in the receptor-binding domain (RBD) and the N-terminal domain (NTD) that are associated with resistance to neutralizing antibodies and monoclonal antibody treatments, de Oliveira said during the South African press briefing.

Richard Lessells, MD, an infectious diseases physician at the University of KwaZulu-Natal in Durban, South Africa, highlighted a few of the most concerning mutations for a South African health journalism center. This includes a cluster of mutations adjacent to the S1/S2 furin cleavage site, which are associated with more efficient cell entry (H655Y, N679K, and P681H).

It also has the nsp6 deletion (similar to one seen with Alpha, Beta, Gamma, and Lambda) that has been associated with immune evasion. Additionally, there are the R203K and G204R mutations in the nucleocapsid protein (seen in Alpha, Gamma, and Lambda) that have been associated with increased infectivity.

Jeffrey Barrett, head of the COVID-19 genomics initiative at the Wellcome Sanger Institute in England, created a color-coded key of the 32 spike protein mutations. Nine of them are red, the most concerning level.

Faust noted that the high number of mutations suggests the variant emerged in a single patient whose body couldn't clear the infection.

Edward Nirenberg, a COVID-19 blogger, cautioned on Twitter that it's "hard to know what the effect of all of these mutations together [will be]. Different mutations interact with each other in complex ways."

Where Has the Variant Been Detected?

So far, 11 countries have reported detecting Omicron to GISAID: South Africa (114), Botswana (19), The Netherlands (12), Australia (5), Hong Kong (5), Italy (4), the U.K. (4), Canada (2), Germany (1), Belgium (1), and Israel (1).

The variant has not yet been detected in the U.S., though experts say it is only a matter of time, as it is likely already here.

Punishing South Africa?

Some South African researchers have raised concerns that they should not be punished for alerting the world to the existence of the variant.

"The world should provide support to South Africa and Africa and not discriminate or isolate it! By protecting and supporting it, we will protect the world!" de Oliveira wrote on Twitter.

Ingrid Katz, MD, of Harvard University, tweeted, "We know what we know BECAUSE South Africa has invested in advanced genomic sequencing. We owe them a debt of gratitude -- not punishment."

The Biden administration issued a travel ban for South Africa and several other African nations late last week. South African president Cyril Ramaphosa has called for the U.S. and other nations, including the U.K. and European Union, to lift their travel bans against his country.

Global authorities have also noted that the emergence of the variant speaks strongly of the urgency to help get vaccine doses to nations in need.

During a WHO meeting on Monday, Richard Hatchett, MD, head of the Coalition for Epidemic Preparedness Innovations (a founder of the global vaccine-sharing initiative COVAX), said the emergence of Omicron "has fulfilled, in a precise way, the predictions of the scientists who warned that the elevated transmission of the virus in areas with limited access to vaccine would speed its evolution."

What's the Bottom Line Right Now?

Bob Wachter, MD, of the University of California San Francisco, summed it up aptly in four steps on Twitter: get vaccinated, get boosted, "get prepared mentally to act more cautiously if Omicron proves to be more infectious, immune-evasive, or both," and "follow the news & science -- will be much clearer in 2-3 weeks."

Indeed, the CDC updated its booster guidance on Monday, now advising that all adults ages 18 and up should get a booster 6 months after their initial mRNA series or 2 months after their Johnson & Johnson shot.

"The recent emergence of the Omicron variant (B.1.1.529) further emphasizes the importance of vaccination, boosters, and prevention efforts needed to protect against COVID-19," the agency said in a statement.

https://www.medpagetoday.com/special-reports/exclusives/95924