“Omicron’s very emergence is another reminder that although many of us might think we are done with COVID-19, it is not done with us."
- Tedros Adhanom Ghebreyesus, WHO Director General
“The temptation to form premature theories upon insufficient data is the bane of our profession.”
- Sir Arthur Conan Doyle’s character Sherlock Holmes
Less than two weeks ago, the World Health Organization (WHO) designated the latest SARS-CoV-2 variant, Omicron, a Variant of Concern (VOC). The reason the WHO moved so quickly in labeling Omicron a VOC was based on early comparisons with the Delta variant. First, Omicron had more than double the number of mutations in its spike protein compared with Delta. Second, in South Africa where researchers first identified the variant, Omicron was spreading twice as fast as Delta.
It is still too soon to answer many of the questions about Omicron. Nonetheless, it is clear that the race is on between Omicron and Delta. In this Germ Gems post, I provide some background information on these two competitors, the “world champion” of all COVID-19 variants (Delta) and the upstart (Omicron).
Recap of the highly destructive Delta variant. Although it feels like an eon ago, SARS-CoV-2 Delta first cropped up as a VOC in India only one year ago. From there it rapidly spread to the U.K. where it supplanted another VOC, Alpha. By March, Delta had found its way to the U.S. where it also outcompeted Alpha. By July 9, 2021 Delta was the dominant SARS-CoV-2 variant in the U.S., and since then it has dominated the world. Of the more than 265 million cases and 5 million deaths caused by COVID-19 so far, the Delta variant rules as Public Enemy No. 1. And it isn’t finished wreaking havoc on the world.
What kind of competitor is Omicron likely to be? When compared to a raging global forest fire caused by the Delta variant, Omicron at first appeared to be just a spark on the horizon. Now that spark seems to be growing. There are three major factors that will determine whether Omicron will oust Delta from its number 1 position.
1) Transmissibility (Contagiousness). Delta has swept the world because
it is highly contagious. Overall, it’s estimated to be twice as contagious as previous variants. As mentioned in earlier Germ Gem posts, the contagiousness of a pathogen is expressed by epidemiologists by the mathematical term R0, pronounced “R naught”—also referred to as the reproduction number. For the Delta variant, R0 is around 5.08, which is much higher than the R0 of the ancestral strain with an R0 of 2.79. This means that for every one person infected with Delta, it is transmitted to roughly five people, whereas one person carrying the ancestral virus can transmit it to between two and three people. Another mathematical term, K, the so-called dispersion parameter, takes into account the superspreading ability of a pathogen. Again, Delta has a commanding K value.
It is far too early to know how Omicron will stack up in terms of contagiousness compared with Delta. But there’s little question that Omicron is on the move. By December 1, 2022, nineteen European countries had reported Omicron cases. In fact, Omicron was found retrospectively to be circulating in some European countries, like the Netherlands, in early November. (This raised the controversial question of where did Omicron actually first emerge? Could it be that it entered southern Africa via a traveler from Europe before the first cases were officially reported in South Africa on November 25?)
Similarly, the Omicron variant is quickly making its rounds in the U.S. Following the first reported case on December 1 in California in a traveler from southern Africa, it popped up in Minnesota on December 2, and by December 5, nearly one-third of U.S. states had detected Omicron.
The early indications suggest increased transmissibility of the Omicron variant, but it is far too soon to calculate it’s R0 value. A superspreading event in early December at a Christmas party in Oslo linked to a Norwegian traveler from South Africa also suggests Omicron has a worrisome dispersion parameter or K value. Again, it is too soon to tell.
Even though there is much yet to be learned about Omicron, the U.S. government’s decision early on to take pages out of Delta’s playbook makes sense. (See December 3 reports by Damian NcNamara in Medscape Medical News, “Feds Go on Offense Ahead of Potential Omicron Spread in US,” and by Sheryl Stolberg in the New York Times, “Emphasizing Tests, Biden Vows to Fight Omicron with ‘Science and Speed.’”) It also makes sense for all of us to continue with vaccinations, including boosters, wearing a mask and practicing social distancing.
2) Evasion of the Immune System. As is the case for Delta, successful spread of the
Omicron variant will be determined by its ability to evade our host defenses (provided mainly by neutralizing antibodies and T cells). Both variants are taking the path of least resistance by picking on the non-immunized. It is not surprising that Omicron got off to its wild start in South Africa, where only about a third of the population was vaccinated.
One of the most pressing questions that remains unanswered is, “Will the current vaccines stop Omicron?” The first cases of Omicron in the U.S. occurred in fully immunized people, which has raised concerns about the efficacy of the vaccines. Early findings give a mixed picture. Some evidence suggests that Omicron is better able to evade the body’s immune system, both to natural infection and following vaccination. The manufacturers of the mRNA vaccines, Pfizer/BioNTech and Moderna, indicated that they are prepared to tweak their vaccines to cover Omicron should the need arise.
So far, it appears that like the Delta variant, Omicron operates as an “opportunistic” pathogen, that is, it takes advantage of people with a compromised immune system. This is why elderly people with waning immunity—immunosenescence—are at greater risk of COVID-19, as are those receiving immunosuppressive drugs. On a related note, this may also explain why Omicron emerged in southern Africa, where HIV/AIDS infections are common, thereby allowing SARS-CoV-2 to circulate for prolonged time periods while it developed more than 40 mutations in its spike protein.
3) Virulence. Some estimates suggest that Delta is twice as virulent as earlier
SARS-CoV-2 variants. The “virulence” of a pathogen is measured by how much damage it inflicts in a host. Virulence is reflected in clinical outcomes, such as, the severity of illness, hospitalization, admission to an Intensive Care Unit, and death. As a rule, when they become infected with SARS-CoV-2, vaccinated individuals are more likely to have milder illness, fewer hospitalizations, and lower mortality.
Again, it’s too early to know whether Omicron is more or less virulent than Delta. While preliminary evidence from South Africa where COVID-19 cases were described as “extremely mild” is encouraging, we must remember that most of these cases occurred in young people. Trends that suggest less severe illness in U.S. cases of Omicron may also be skewed by the vaccination status of those who become infected.
One might think that genetic changes that increase virulence are most likely to benefit a virus. But it is also possible that in the long-run a variant with attenuated (reduced) virulence will win the race. While teleological arguments are generally unacceptable scientifically, one could argue that it would be preferable for a viral variant to be less virulent allowing its host to survive and serve as a potential target again sometime in the future. This notion is supported by the recent discovery that Omicron has adopted a gene insertion from a seasonal coronavirus that causes the common cold. While this scenario is largely an optimistic conjecture, if it is true, it would be one that we all could live with—quite literally.
And the winner is… It is reassuring that since the emergence of Omicron two weeks ago and its being detected in 38 countries, no deaths have been reported as yet. But we still have much to learn about Omicron’s transmissibility, how it evades the immune system, and its virulence. It is far too early to predict which variant will win the race. As the 5thcentury BC Chinese philosopher Lao Tzu warned, “Those who have knowledge don’t predict. Those who predict, don’t have knowledge.”
