Omicron and BA.5: A Guide to What We Know

[Originally published: Dec. 2, 2021. Updated: Sept. 7, 2022]

COVID-19 has moved at a rapid pace since Omicron surfaced last Thanksgiving and spread like wildfire. Since then, multiple Omicron subvariants have emerged. In late August 2022, a strain called BA.5—the most contagious one so far along with BA.4, another subvariant—is causing more than 88% of cases, making it the predominant strain in the United States. (BA.4 accounts for about 8% of all U.S. COVID cases.)

The original Omicron strain has a relatively mild version of the virus, causing less severe disease and death than Delta, which preceded it. While scientists are still learning about BA.5, data continues to show hospitalizations  to be low compared to earlier in the pandemic. So far, the same can be said of infections, based on numbers from the Centers for Disease Control and Prevention (CDC). But that data does not include results from home tests.

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 so far.

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. By late December, Omicron was the predominant strain in the U.S. As people around the world welcomed a new year, Omicron continued to surge more quickly than any previous variant 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. 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. 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 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 variants. BA.4 and BA.5 are thought to be even more transmissible.

The second question has been whether Omicron—and currently the BA.4 and BA.5 variants—is more likely than Delta or other variants to cause severe disease. While there is more to learn about BA.5, early data from South Africa has not shown a sharp rise in deaths from the subvariant. 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 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. Experts are saying that the BA.4 and BA.5 subvariants seem to have the ability to elude some of the antibodies produced after vaccinations and infections, including those caused by some Omicron subvariants. 

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. 

But in January, the CDC did report that 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. 

In August 2022, the FDA authorized both a bivalent Pfizer-BioNTech booster shot for people 12 years of age and older, and a bivalent Moderna shot for adults 18 and older. These boosters are designed to protect against disease caused by the original strain of the SARS-CoV-2 virus, as well as the Omicron variant. Individuals can get the booster shot starting two months after completing the two-dose primary series or receiving a previous booster dose.

People need to understand that variants like Omicron and BA.5 are a natural part of the progression of the virus, Grubaugh says. New variants aren’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.”