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Hybrid immunity offers increased protection that is longer-lasting against Covid-19 reinfection, studies show

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By Tasnim Ahmed, CNN

Pfizer/BioNTech’s Covid-19 mRNA vaccine provides an added layer of protection against reinfection for people who have been previously infected with Covid-19, as well as increased immune durability over time, according to two studies published Wednesday in the New England Journal of Medicine.

The studies offer more insight into the concept of hybrid immunity: when previously infected people, who have “natural immunity,” then get vaccine-acquired immunity.

One of the studies, conducted out of Israel, found that amongst people who had recovered from Covid-19 infections, reinfections were over four times more common in those who did not receive vaccines than in those who did after the primary infection. However, the study, which involved over 149,000 people with a history of Covid-19 infection, also found that the effectiveness of the Pfizer vaccine is lower in adults over 65. The vaccine was 82% effective among people 16 to 64 years old and only 60% effective in those 65 and older. This study was conducted between March 1, 2021, and November 26, 2021, encompassing the surge of the Delta coronavirus variant in Israel.

The study also found that there was no significant difference in vaccine effectiveness if people who were previously infected received one dose or two doses, supporting evidence from other studies that showed one dose was sufficient in protecting people with prior Covid-19 infections from reinfection.

These findings may have implications for vaccine policies.

Shane Crotty, a virologist and professor with the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology, told CNN that it would be “quite reasonable” to have a policy in the US that required people with previous coronavirus infections to get only one dose of a vaccine, based off the results of this research. Crotty was not involved with either study.

Ronen Arbel, lead researcher on this study and a health outcomes researcher at Clalit Health Services in Israel, believes that more countries should adopt a policy like what the Israeli Ministry of Health implemented in March 2021, when it recommended a single dose of vaccine for people who had recovered from Covid-19, to be given three months after their primary infection.

“If you recovered from Covid-19, it’s like you got a primary vaccination,” Arbel told CNN. “You should get vaccinated, but once is enough. It’s sort of like a booster.”

The second new study, conducted in the United Kingdom, demonstrated that immunity is more durable and longer-lasting in people who had recovered from Covid-19 infection before receiving a Pfizer vaccine.

Among participants who were not previously infected, two doses of the vaccine were associated with an 85% drop in risk of infection two months after vaccination. However, that number would fall to 51% six months after vaccination. In contrast, those who were vaccinated after recovering from Covid-19 maintained over 90% protection more than a year after primary infection and over six months after vaccination.

“It may be that seeing the whole virus in some form to produce broad immune responses along with a deepening of the immune response with vaccination (either before or after) confers the super immunity,” said Dr. Monica Gandhi, associate chief of the Division of HIV, Infectious Diseases and Global Medicine at the University of California, San Francisco, who was not involved with either study.

The UK research used data from the SIREN study on health care workers. The over 35,000 participants were followed between December 7, 2020, and September 21, 2021, and had PCR testing for Covid-19 every two weeks. It found that among people who were previously infected, the risk of reinfection was 86% less than the risk of primary infection in unvaccinated people. However, this protection fell to 69% more than a year after infection, indicating that primary infection alone does not provide durable immunity.

According to Crotty, hybrid immunity allows the body to create more diverse antibodies to neutralize a wider variety of variants. This also happens with full vaccination and a booster, but it happens much faster with infection followed by vaccination.

“Hybrid immunity has got a whole bunch of additional bonuses to it. One, that these studies are showing quite presently, is durability. Durability is quite robust,” Crotty said.

Although both studies add to growing evidence that hybrid immunity can offer increased protection against future Covid-19 infections, neither includes data from the surge of the highly transmissible Omicron variant.

“The overall risk to be reinfected is much higher with Omicron than with Delta. Does the vaccine protect [against Omicron]? We can hypothesize that it does, but we don’t have the data yet,” Arbel said.

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