Previous Non-Omicron SARS-CoV-2 Infection May Protect Against Infection of Omicron

Prior infection with SARS-CoV-2 decreased the risk of being reinfected with Omicron among unvaccinated and vaccinated individuals.

The Omicron variant of SARS-CoV-2 had a higher transmissibility and spread than any previous variant, even among countries with a high percentage of vaccinated individuals. To mitigate risk and Omicron spread, researchers examined previous infections, vaccination, and the risk of Omicron, in a study published in JAMA Network Open.

Researchers found that hybrid protection—prior SARS-CoV-2 infection and vaccination—could best reduce the risk of Omicron, at almost 50%. Among unvaccinated individuals, those who were previously infected with severe SARS-CoV-2 infections had more protection against reinfection of Omicron.

“Overall, strong and sustained protection from prior heterologous infection against severe Omicron outcomes, including the absence of Omicron-associated deaths among survivors of prior infection, seems to be a common interpretation across the few available studies to date, including ours,” the study authors wrote.

Prior SARS-CoV-2 infection reduced the risk of hospitalization from Omicron by 80%. This percent increased to 94% in those with a hybrid protection of 2 doses, and 97% with hybrid protection of 3 doses.

Researchers conducted a test-negative case-control study to examine the protectiveness of a previous non-Omicron SARS-CoV-2 infection against reinfection of Omicron. The researchers also looked at the protectiveness of 3 doses of an ancestral, Wuhan-like messenger RNA (mRNA) vaccine on participants who had/had not previous heterologous non-Omicron SARS-CoV-2 infection.

Among a cohort of 696,439 patients, researchers identified 4.2% of case participants who were previously infected with a SARS-CoV-2 variant that was not Omicron and 6.3% of the control group participants were infected with a non-Omicron strain.

After looking at the laboratory-confirmed cases and stratifying analyses by severity and time since primary infection and/or vaccine dose, researchers found that the risk of being reinfected with Omicron was reduced by 44% among nonvaccinated and prior infected individuals.

Vaccinated individuals had better odds against reinfection with Omicron and protection increased with each new vaccination. Participants who were previously infected with SARS-CoV-2 and received 1 dose of the vaccine had a 65% reduced rate of reinfection with Omicron. Having 2 doses lowered the risk of reinfection by 68% and 3 doses reduced the risk by a median of 83%.

“Prior infection improved vaccine protection (and vice versa) during the Omicron period,” the study authors wrote.

Individuals who were not previously infected with SARS-CoV-2 but who received vaccine doses decreased their risk by 20%, 42%, and 73% with each respective increase in dose.

The study has limitations, particularly because researchers are believed to have underestimated the protection of prior infections. Additionally, the data may have lower sensitivity to estimation biases. Finally, the study authors excluded specimens from revaccinated individuals within 90 days of doses 2 and 3.

“The findings of this study suggest that vaccination with 2 or 3 mRNA vaccine doses among individuals with prior heterologous SARS-CoV-2 infection provided the greatest protection against Omicron-associated hospitalization,” the study authors wrote.


Carazo, Sara, Skowronski, Danuta, Brisson, Marc, et al. Estimated Protection of Prior SARS-CoV-2 Infection Against Reinfection With the Omicron Variant Among Messenger RNA–Vaccinated and Nonvaccinated Individuals in Quebec, Canada. JAMA Netw Open. 2022;5(10):e2236670. doi:10.1001/jamanetworkopen.2022.36670