Omicron and its Subvariants: A Guide to What We Know

[Originally published: Dec. 2, 2021. Updated: Feb. 3, 2023]

Note: Information in this article was accurate at the time of original publication. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.

In the battle against COVID-19, Omicron has proven to be a difficult opponent. After emerging in other parts of the world, the variant of the SARS-CoV-2 virus that causes COVID-19 surfaced in the United States toward the end of 2021 and spread like wildfire. Since then, multiple Omicron subvariants have emerged, some of them more adept than others at evading immunity from vaccination or previous infection.

In early 2023, a new Omicron subvariant called XBB.1.5,  the most transmissible strain of the virus so far, was predominant in the U.S. Cases were also believed to be rising with people spending more time in doors and attending recent holiday gatherings, with fewer wearing masks and taking other mitigation measures. Experts are still trying to better understand XBB.1.5 and other Omicron subvariants, such as BQ 1.1., which continue to circulate. They are also monitoring more than 300 other descendants of Omicron around the world.

Tracking Omicron and its variants can easily become confusing—even overwhelming, but Yale Medicine follows these variants, and the CDC provides weekly updates to track them.

Thomas Murray MD, PhD, a Yale Medicine pediatric infectious diseases specialist, and Nathan Grubaugh, PhD, an epidemiologist at the Yale School of Public Health, commented on what we know.

First, some background. Omicron was initially identified in Botswana and South Africa in November 2021—although later reports showed earlier cases in the Netherlands. On December 1, the CDC confirmed the first case in the U.S., in an individual in California who had returned from South Africa in November. Omicron was the predominant strain in the U.S. by late December. As people around the world welcomed a new year, the variant continued to surge more quickly than any previous strain in many areas. Both the WHO and the CDC classified it as a "variant of concern."

Early reports from South Africa indicated that most cases were mild—and that symptoms for this variant seemed to be different. “The reports show that patients in South Africa—many of whom were young—have had severe fatigue, but no loss of taste or smell,” says Lauren Ferrante, MD, a Yale Medicine pulmonologist.

But some people infected with Omicron still developed severe disease and had to go to the hospital, and some died. For that reason, experts continued to express concerns that a large volume of cases in a particular area could overwhelm medical centers, making it difficult to treat severe cases.

From the beginning, two important questions about Omicron were top of mind for scientists, says Dr. Murray. As new variants have emerged, the first question has been how transmissible each one is compared to its predecessor.

According to the CDC, the Omicron variant spreads more easily than the original SARS-CoV-2 virus and the Delta variant. In its early days, the variant caused an alarming spike in COVID-19 cases in South Africa—they went from 300 a day in mid-November 2021 to 3,000 a day at the end of that month. In the first months of 2022, an Omicron subvariant called BA.2 began to spread even faster than other Omicron subvariants, followed by BA.4 and BA.5, only to be outdone by the BQ subvariants.

The second question has been whether Omicron and its subvariants are more likely than their predecessors to cause severe disease. While there is more to learn about the latest variants, experts are hoping prior immunity will be of some help. The original Omicron caused a record number of cases, but while it has also caused its share of hospitalizations and deaths, factors such as lengths of hospital stays, ICU admittance, and death were “lower than during previous pandemic peaks,” according to a CDC report in January 2022.

The CDC says the presence of severity of symptoms can be affected by vaccination, history of prior infection, and age and other health conditions.

The Food and Drug Administration (FDA) has authorized bivalent vaccine booster shots (also called “updated” vaccines) from Pfizer-BioNTech and Moderna for most people ages 6 months and older. Bivalent means the shot protects against two strains of a virus, and these COVID-19 boosters are designed to protect against both the original SARS-CoV-2 virus and the Omicron BA.4 and BA.5 subvariants. A bivalent shot is available to people two months after they’ve completed the two-dose primary series or received a previous booster dose.

In January, two studies suggested the updated vaccine has continued to be effective against emerging Omicron strains. The New England Journal of Medicine (NEJM) published a study based on people 12 and older included in North Carolina’s state vaccine registry data that found it to be 58.7% effective against hospitalization compared to 25% for the monovalent one that preceded it; its effectiveness against infection was 61.8% compared to 24.9% for the monovalent. The study covered a period when Omicron BQ.1 and BQ.1.1. were also circulating, in addition to the strains the booster was designed to target.

Another study, from the CDC, assessed the bivalent vaccine’s real-world effectiveness against Omicron’s newest strains, XBB and XBB.1.5, in people who had previously received two to four monovalent vaccine doses. Scientists found that—at least for the first three months after vaccination—the updated booster’s effectiveness against the XBB subvariants was similar to what it was against BA.5.

Novavax also offers a booster shot, but it protects against the original SARS CoV-2 virus and may not protect against recent Omicron subvariants. The company says it expects to have a vaccine that will protect against the recent Omicron subvariants in 2023.

Paxlovid, which is given in pill form early in the course of infection, is still prioritized by the National Institutes of Health (NIH).

Research published in the Annals of Internal Medicine in December 2022 suggest the drug can offer a substantial benefit as far as protection against severe illness and hospitalization among vaccinated people over the age of 50 (clinical trials had only reported on Paxlovid’s efficacy in unvaccinated people). Data for the study was gathered from a period between January and July 2022, when previous strains of Omicron were circulating. Another treatment, remdesivir, is also expected to be effective against Omicron.

Two other treatments, both monoclonal antibodies, had their FDA authorization halted until further notice in response to data that showed they were not effective against the Omicron subvariants that were currently circulating. In December 2022, the FDA withdrew its EUA for bebtelovimab, which was used as a treatment. It withdrew its EUA for Evusheld in January. The latter was the only option for pre-exposure prophylaxis (or preventive medicine) for immunocompromised individuals.

When they first started to study Omicron, scientists were concerned about a key distinguishing factor in the variant. Unlike Delta and other coronavirus variants, it carries an abundance of mutations—about 50 in all, including 26 that are unique to the variant—and more than 30 on the spike protein, which is the viral protein that vaccines train the immune system to recognize and attack. Grubaugh said some of Omicron’s enhanced transmissibility could come from its ability to evade some immune responses, especially in people who were previously infected, but not vaccinated.

Scientists also wanted to know if these mutations indicated a possible reduction in the effectiveness of the COVID-19 vaccines and certain monoclonal antibody treatments. “We don’t really know how the mutations work together. Not everything is additive,” Grubaugh had said.

People need to understand that variants like Omicron are a natural part of the progression of the virus, Grubaugh says.

New variants aren’t surprising, he says. No one can predict how they might evolve—or if they will simply vanish at some point. “Delta was never going to be the last variant—and Omicron is not going to be the last one," Grubaugh says. "As long as there is a COVID-19 outbreak somewhere in the world, there is going to be something new that emerges.”