Omicron’s Trajectory Shows Challenge of Maintaining Immune Defenses

These recurring run-ins with a changing virus demonstrate the challenge of maintaining long-lasting defenses, even as Covid-19 vaccines and exposures build up protection against the virus’s worst outcomes.

“This is not a virus that a one-shot or a one-time infection gives you lifelong immunity,” said Jodie Guest, vice chair of the epidemiology department at Emory University’s Rollins School of Public Health. “And we’re now super-aware of that.”

A nationwide survey of blood donors published by the CDC estimated that about 94% of people ages 16 and up had some antibodies to the SARS-CoV-2 virus by November 2021, either through vaccination or prior infection. The U.S. had just come off a wave sparked by the Delta variant, and some hoped the country might have reached a turning point.

Then Omicron hit. A significant number of mutations helped it dodge our built-up immune responses, immunologists and epidemiologists said. Protection from prior infection and vaccination declined, studies found, and booster doses to guard against the virus became more imperative.

Data indicate Omicron triggered big surges in reinfections while it also pushed tallies of known cases to record highs.

“We knew before Omicron that SARS-CoV-2 was capable of some immune escape,” said Sarah Cobey, an associate professor of ecology and evolution at the University of Chicago. “Omicron made it clear that these adaptations could sometimes be leaps.”

Rhode Island’s health department estimates 3.2% of reported cases during the state’s Delta-variant surge last year were reinfections. The known reinfection rate there jumped to 13.3% from late December to mid-January. Data from Minnesota show the percentage of reinfections reaching similar highs early this year, during the Omicron surge.

States including New York, Louisiana and Washington are also collecting data on reinfections, which are generally considered to be new after 90 days. Health departments broadly acknowledge their counts are low because so many people go untested or use at-home tests, making reinfections particularly hard to track.

Vaccinated people had lower rates of infection and severe outcomes during the surge than the unvaccinated, despite an increase in breakthrough cases, CDC data show. Colorado, a state that breaks out reinfection data by vaccination status, counted the highest number during Omicron among unvaccinated people and the lowest number among boosted people.

Arriving nearly two years into the pandemic, Omicron also caught many people with diminished protection long after their first exposure or latest vaccination. Protection against Covid-19 infection wanes in the months after vaccination or exposure, evidence suggests.

The jump in reinfections is “correlating with Omicron, and it is also correlating with waning immunity,” said Umair Shah, secretary of health in Washington state.

Weekly Covid-19 reinfections

200 per 100,000 population

Weekly Covid-19 reinfections

200 per 100,000 population

Weekly Covid-19 reinfections

Protection against severe disease can also diminish but appears to be more stable. The Omicron wave didn’t hospitalize or kill people at the same rate as earlier variants, likely because of built-up immune protection in the population, immunologists said.

“What we’ve seen with Omicron is a tremendous amount of infections. Not as many have translated to severe disease,” said Alessandro Sette, a professor at the La Jolla Institute for Immunology in California. “Vaccine efficacy against severe disease holds much better.”

Still, the explosion in cases still triggered the second-highest peak in reported deaths, and the sheer number of sick people strained hospitals. CDC data suggests that more than half of people in the U.S. have infection-induced antibodies, up from 34% in December.

Now, those infections from the Omicron surge are likely helping to blunt the effect of an Omicron subvariant, BA.2, that is currently dominant in the U.S. Some health officials and experts hope that built-up protection from Covid-19 vaccination and exposures is reaching a point where the virus is less dangerous for most people and its spread less disruptive.

But even mild Covid-19 cases can lead to lasting complications, public-health experts said, and the full health risks associated with repeated exposures aren’t clear. New variants could also spoil hard-won progress, they said, particularly if the virus spreads unimpeded. 

“To decrease the changes, it’s about decreasing the space the virus can actually play in and limiting that space to evolve,” said Ali Ellebedy, an immunologist at Washington University School of Medicine in St. Louis.

Research that hasn’t been peer-reviewed suggests that other Omicron subvariants, such as BA.2.12.1, may better escape the immune responses from the Omicron variant that surged this winter. The CDC estimates BA.2.12.1 recently represented 36% of U.S. cases.

This fall will likely present another test. Respiratory viruses tend to flare as people congregate indoors, and people hit during the Omicron wave will be many months past their infections. Meantime, only about half of eligible people in the U.S. have gotten a booster shot, underscoring the challenge of asking people to repeatedly roll up their sleeves to bolster their protection.

“We will get exposures,” said Adolfo García-Sastre, director of the Global Health and Emerging Pathogens Institute of the Icahn School of Medicine at Mount Sinai in New York. “The question is how often, and what is the percentage of severe disease?”

Write to Brianna Abbott at brianna.abbott@wsj.com and Jon Kamp at jon.kamp@wsj.com