That Omicron, the widely-feared new variant of the novel coronavirus, this week made its first appearance in the United States, in California, and now has emerged with a second case in Minnesota, is not a surprise. The fact that Omicron was in several European countries, Australia, Hong Kong, and Canada meant the new strain of the virus already had quickly spread across the globe. And it appears as if this latest American patient may have been exposed to the variant within the United States.
This is not as ominous a sign as one might think, given that many of the variants—even those that haven’t accelerated to cause major outbreaks—were found on several continents more or less simultaneously with their initial discovery. After all, by the time we realized the original SARS-2 coronavirus was emerging from central China, it was likely already in southern Europe, and by the time we implemented a travel ban from China, SARS-2 had almost certainly entered New York City after traveling from southern Europe to ignite the first epidemic there in the spring of 2020.
The point is that the discovery of Omicron on multiple continents is not unusual and does not in itself portend anything dire. Similarly, there is no clear evidence that Omicron causes unusually severe disease, and initial accounts suggest there are many mild cases. That said, we should not be too swayed by anecdotes of mild Omicron cases: Broadly speaking, the spectrum of clinical severity among the different variants has been pretty similar. In the end, COVID-19 is a bad illness to get because of significant rates of hospitalizations and long COVID symptoms. We should assume Omicron will be equally awful.
ADVERTISEMENT
So then, exactly what should we worry about regarding the Omicron variant? I suggest one plausible scenario, based on what relatively little we know right now, is the emergence of separate, twin outbreaks, where the currently-dominant Delta variant continues to ravage unvaccinated people in the United States, even as Omicron targets people who are partially immune—either from previous infection or incomplete vaccination.
Omicron’s transmissibility is still coming into focus, and it appears to have rapidly accelerated in Pretoria, Johannesburg, and elsewhere in South Africa. However, the bigger question is whether Omicron is so transmissible that it can outcompete or overtake the Delta variant in North America, Europe, and elsewhere.
Ultimately, this has been the real story of the COVID-19 pandemic. The original lineage from central China gave way to the Alpha variant that first arose out of England in 2020. Later, Alpha gave way to Delta, which arose from India in 2021. Now, in 2022, the question looms as to whether Omicron might displace Delta if it is more transmissible.
While this is a possibility, looking at the key sequences in the furin cleavage site around the S (spike) protein or those in the N (nucleocapsid), many of the mutations found in Omicron are the same as those in Alpha. So the potential is there that Omicron will resemble Alpha in its transmissibility—still high, but not as high as Delta. Only time will tell, but for now, I could envision that Delta will continue to circulate in the U.S., meaning it won’t go away anytime soon, unlike other displaced variants.
But the Omicron variant does have one additional advantage to ensure that it will stick around, which has helped stoke much of the concern and even panic around it. Even if it does not displace Delta, it appears to have an added fitness advantage (to loosely use an evolutionary term) of escaping host immune responses, especially partial-immune responses to previous SARS-2 virus lineages.
Therefore, it would not surprise me if we start to see Omicron reinfections among those who were infected earlier with another variant but decided not to get vaccinated, or those who had only two doses of the mRNA vaccine but experienced waning immunity. The first Omicron case in the United States appears to fall into the latter category.
So here is what we might see unfold in 2022: Both variants circulate in the U.S., with the Delta variant disproportionately affecting the totally unvaccinated, while Omicron causes reinfections among those who have not been vaccinated but infected previously, or those who have not received their booster (third mRNA immunization). And of course, this won’t be cut and dried or black and white—there will be overlap.
What about those who received three mRNA immunizations, will they be protected against the Omicron variant? It’s difficult to say, but given that the third immunization often provides a 30-40 fold rise in virus-neutralizing antibodies to the original variant, I’m still hopeful that this will provide sufficient levels of virus-neutralizing antibodies to cross over (or as Tony Fauci says, “spillover”) to neutralize the Omicron variant. In this case, three immunizations of our existing mRNA vaccines might still stop symptomatic or severe illness, and even possibly infection. The scientists at our Texas Children’s Hospital Center for Vaccine Development are now looking at this for our recombinant protein vaccine, and we know scientists at Pfizer-BioNTech, Moderna, and other pharma companies are doing the same.
A bottom line is that whether you are concerned about Delta, Omicron, or both, your strategy to protect the health of you or a loved one is the same. Get your third mRNA immunization if you are eligible and haven’t done so already. If you have been infected previously, get vaccinated. And vaccinate your kids.
Also, even as Moderna and other companies announce they are working to design an Omicron-specific booster, don’t wait for it or delay boosting. The new Omicron-specific booster might never materialize, and we don’t even know if an Omicron-specific booster would provide better or specific protection against the Omicron variant.
What we do know is that the current booster provides additional benefits in terms of protecting against Delta and even some very early (unpublished) data from Israel suggest it may work against Omicron as well.
Finally, keep in mind that this is a fluid situation. We are learning something new about Omicron daily, and this scenario provides an early roadmap of how to think through this very thorny problem of a potentially troublesome new variant. Almost certainly, it will require modification as the data pour in over the coming days and weeks.
