The Omicron BA.4 and BA.5 subvariants of SARS-CoV-2 were found to be more stealthy in evading people’s immune defenses than any of their predecessors.
But recent research shows that prior infection with an older variant (such as Alpha, Beta, or Delta) offers some protection against reinfection with BA.4 or BA.5, and that prior infection with Omicron is significantly more efficient. This is the conclusion of a study that assessed all COVID-19 cases in Qatar since the wave of BA.4 and BA.5 infections began.1.
The work, which was posted to the medRxiv preprint server on July 12 and has not yet been peer-reviewed, feeds into broader research into “how different immunities combine with each other,” the co says. -study author Laith Abu-Raddad, an infectious-disease epidemiologist at Weill Cornell Medicine-Qatar in Doha.
Everyone has a different immune story, as people have received different combinations of COVID-19 vaccines and been infected with various variants during the pandemic. “Different histories endow people with different immunity against future infection,” says Abu-Raddad. Knowing how these various immune responses interact inside a person will be “very important for the future of the pandemic”, he adds.
To see how well the previous infection provides protection against both Omicron subvariants, Abu-Raddad and colleagues analyzed COVID-19 cases recorded in Qatar between May 7 this year – when BA. 4 and BA.5 entered the country for the first time – and on July 4. They looked at the number of people known to have been previously infected who tested positive or negative for COVID-19, and identified which infections were caused by BA.4 or BA.5 by examining positive test samples to see s they contained a protein that these subvariants lack.
Researchers found that infection with a pre-Omicron variant prevented reinfection with BA.4 or BA.5 with 28.3% efficacy and prevented symptomatic reinfection with either subvariant with an efficiency of 15.1%. Prior infection with Omicron conferred stronger protection: it was 79.7% effective in preventing BA.4 and BA.5 reinfection and 76.1% effective in preventing symptomatic reinfection.
Although it seems counterintuitive to see stronger protection against any reinfection than symptomatic reinfection, the researchers say this effect is consistent with previous studies and is likely caused by the estimates having wide confidence intervals.
Time between infections
“It’s a good study,” says Kei Sato, a virologist at the University of Tokyo. But he points out that the length of time between the first and second infection may have influenced the results. Earlier variants have been around longer than Omicron, which only appeared in late 2021. And several studies, including one by the same team in Qatar2showed that natural immunity against SARS-CoV-2 declines over time.
Alex Sigal, a virologist at the Africa Health Research Institute in Durban, South Africa, agrees. ” The time that [has] past since your original infection is much shorter with Omicron, so it’s really not a fair comparison,” he says. Sigal adds that participants’ vaccination statuses are unclear from the results, as is information about whether primary infections occurred before or after vaccination, which could be an important consideration.
Abu-Raddad says the purpose of the study was to investigate who is currently most prone to reinfection, rather than attributing natural immunity to a particular viral strain. He says the study design controls for the effects of vaccination, and the team conducted a sensitivity analysis to adjust for vaccination status, the results of which were consistent with the overall conclusions.
“The immunity you get from these Omicron infections actually protects you from other Omicron sublines to some degree,” says Sigal. However, “COVID is everywhere,” Sato warns. “It can easily evolve into a new variant.”