Omicron and Its Subvariants: A Guide to What We Know

[Originally published: Dec. 2, 2021. Updated: June 8, 2022]

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.

COVID-19 has moved at a rapid pace in the past several months. Last fall, not long after the Delta variant moved past its peak and people started to prepare for Thanksgiving, Omicron surfaced and began to spread like wildfire. The good news was that the new variant caused less severe illness and death than Delta. But it was also highly transmissible—more contagious than any variant that came before it.

Then, in the first months of 2022, experts turned their focus to Omicron BA.2, a genetically distinct subvariant of Omicron (or BA.1), which soon became the predominant variant in the United States. It was soon overtaken by another spinoff called BA.2.12.1. In early June, infections were multiplying from two other Omicron subvariants, BA.4 and BA.5, estimated by the CDC to make up 13% of new cases, up from 7.5% only a week before.

Scientists are still investigating whether the newest variants are more contagious or dangerous than their predecessors.

Tracking these 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 first identified in Botswana and South Africa in November—although later reports showed earlier cases in the Netherlands. The first case in the U.S. was reported on Dec. 1 of last year in California. By late December, it became the predominant strain in the U.S. Both the WHO and the Centers for Disease Control and Prevention (CDC) have classified Omicron as a “variant of concern.” BA.2 was discovered by scientists in November 2021, and the first case was reported in the U.S. in January.

The Omicron variant caused an alarming spike in COVID-19 cases in South Africa—cases went from 300 a day in mid-November to 3,000 a day at the end of that month. It’s also been identified in at least 185 countries, according to the New York Times COVID-19 tracker.

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.

As people around the world welcomed a new year, Omicron surged more quickly than any previous variant in many areas. The new variant drove a rising caseload in the U.S. that, at the end of 2021, far surpassed the record for new daily cases. However, numbers of hospitalizations and deaths were still far below what they were during previous virus peaks.

From the beginning, two important questions about Omicron were top of mind for scientists, says Dr. Murray. The first was how transmissible the new variant is compared to Delta, previous variants like Alpha and Beta, and the original virus.

According to the CDC, the Omicron variant spreads more easily than the original SARS-CoV-2 virus and the Delta variant, and BA.2 spread even faster  than BA.1.

The second question is whether Omicron—and BA.2—is  more likely than Delta or other variants to cause severe disease—if most infections continue to turn out to be mild, rapid transmission would be less of a threat, Grubaugh says. Omicron has 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 have been “lower than during previous pandemic peaks,” according to a CDC report in January.

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

There is a third—and likely most important—question that has to do with how protective the existing vaccines will be against the new variant, says Dr. Murray. Studies have shown that people who are fully vaccinated and have gotten boosters have strong protection against hospitalization from both BA.1 and BA.2.

Soon after Omicron’s appearance, scientists were concerned about a key distinguishing factor in the variant. Unlike Delta and other coronavirus variants, this one 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.

But in January, the CDC reported a third vaccine dose, or booster, was “highly effective” at preventing the need for visits to urgent care or hospitalization due to COVID-19. In March, after some early evidence that prevention from the first booster shot was waning in older people, the U.S. approved a second booster for people older than 50 and those with certain immune deficiencies, giving those groups the option of another preventive dose.

As far as treatments, both BA.1 and BA.2 have shown an ability to evade most monoclonal antibody treatments authorized by the Food and Drug Administration. The antiviral drugs Paxlovid, molnupiravir and remdesivir have been effective against severe disease from both BA.1 and BA.2 when taken soon after diagnosis, and so has Evusheld, which is designed to protect people who have not been infected.

People need to understand that variants like Omicron and BA.2 are a natural part of the progression of the virus, Grubaugh says. “The fact that there is a new variant isn’t surprising,” he says. “Delta was never going to be the last variant—and Omicron is not going to be the last one. As long as there is a COVID-19 outbreak somewhere in the world, there is going to be something new that emerges.”

Both Grubaugh and Dr. Murray say the best way to prevent new variants is to get vaccinated and get a booster shot, because if more people are fully vaccinated, it decreases the opportunity for the virus to spread and mutate. Recommendations for boosters have been changing, and updated information is available on the CDC website.

Meanwhile, Omicron and BA.2 are still threats in the U.S., and experts continue to recommend following CDC infection prevention strategies.