Although prior infection and vaccination offer similar levels of protection against the omicron subvariants BA.1 and BA.2, infectious disease experts say when it comes to newer omicron variants, such as BA.4 and BA.5, natural immunity is likely less protective against infection.

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How vaccine, natural immunity fares against BA.1 and BA.2

According to a new study published in the New England Journal of Medicine, protection against symptomatic Covid-19 infection from the BA.1 or BA.2 subvariants was similar across different types of immune protection, including three doses of a vaccine, prior infection, and both vaccination and prior infection.

For the study, researchers from Qatar examined data from the country's national databases on Covid-19 vaccination, laboratory testing, hospitalization, and death from Dec. 23, 2021, and Feb. 21, 2022. During this time, the omicron subvariants BA.1 and BA.2 drove a surge of cases in the country.

Using the databases, researchers divided patients in five different groups based on the type of immunity they had:

• Prior infection without vaccination
• Two vaccine doses but no prior infection
• Two vaccine doses and prior infection
• Three vaccine doses but no prior infection
• Three vaccine doses and prior infection

Overall, the researchers found that individuals who had three vaccine doses as well as prior infection had the strongest protection against infection (77%), followed by those who had two vaccine doses as well as prior infection (55%), those who had three vaccine doses (52%), and those who had a prior infection alone (46%).

However, individuals who received only two vaccines had essentially no protection against infection—although their protection against severe illness remained robust at 76.8%. The other types of immunity also showed similar effectiveness against severe illness, ranging from 73.4% for prior infection alone to 100% for three vaccine doses and prior infection.

"Even though the five forms of immunity investigated showed large differences in protection against symptomatic infection that ranged from 0 to 80%, they all showed strong protection against COVID-19-related hospitalization and death," wrote Laith Abu-Raddad, an infectious disease epidemiologist at Weill Cornell Medicine-Qatar, and his colleagues. "This suggests that any form of previous immunity ... is associated with strong and durable protection against COVID-19-related hospitalization and death."

Does immunity from BA.1/BA.2 hold up against newer subvariants?

According to infectious disease experts, prior infection from BA.1 or BA.2 may be protective against reinfection by the same subvariants, but they are not likely to hold up against newer subvariants, such as BA.4 or BA.5, which are currently growing in prevalence. Based on CDC data, BA.4 and BA.5 currently make up around 20% of all new Covid-19 cases in the United States.

"It's expected that there's probably not much cross-protection between" BA.1/BA.2 and BA.4/BA.5, said Amesh Adalja, an infectious disease physician at the Johns Hopkins Center for Health Security.

Similarly, James Lawler, from the University of Nebraska Medical Center's Global Center for Health Security, said that it's "quite likely and highly predictable that people who were infected with BA.2 will be susceptible to infection with BA.4 or BA.5, and that susceptibility will grow as time goes on, as you get further away from your prior infection."

Adalja agreed with Lawler's assessment that susceptibility to reinfection from BA.4 or BA.5 will increase over time, but he also noted that the durability of protection may now be shorter since the various omicron subvariants are so different from each other.

"BA.2 is as different from BA.1 as Delta was from Alpha … in terms of the number and types of mutations," Lawler said. "I think they're different enough that we need to be treating them as if they're completely distinct variants."

Although protection against reinfection "would be expected to be months if there are no immune-evasive changes[,] [n]ow, it's probably a matter of weeks to a month," Adalja said.

Overall, substantial genetic changes to the coronavirus and its variants are expected, and "[t]he virus is going to be able to continue to evolve to reinfect us at will," according to Adalja. In order to face these new variants, vaccines, boosters, antivirals, and other forms of protection will be needed.

"In general, we should expect reinfection," Adalja said. "It's really about making sure reinfections are mild." (Ingram, MedPage Today, 6/16; Fiore, MedPage Today, 6/16)