Effectiveness of previous COVID-19 and vaccination against SARS-CoV-2 Omicron infection

In a recent study published in The New England Journal of Medicine (NEJM), researchers studied the effects of prior immunity on symptomatic infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.

Study: Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections. Image Credit: petovarga/Shutterstock
Study: Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections. Image Credit: petovarga/Shutterstock


The Omicron wave in Qatar began on December 19, 2021, and reached its peak by mid-January 2022. While the Omicron BA.1 subvariant was predominant in the country during the first few days, the BA.2 subvariant replaced BA.1 and prevailed as the dominant variant. Although considered as subvariants, substantial genetic distance exists between the two.

The protection against these subvariants by prior SARS-CoV-2 infection, vaccination, or both (hybrid immunity induced by infection and vaccination) is not yet fully defined.

About the study

In the present study, researchers assessed the protective immunity conferred by the previous infection with variants other than Omicron, coronavirus disease 2019 (COVID-19) vaccination, and hybrid immunity against symptomatic BA.1 or BA.2 infection. Effectiveness against severe and critical illness and death was also estimated. Data on COVID-19 vaccination, testing, hospitalization, and death were obtained from national federated databases, encompassing COVID-19-related information and associated demographics.

Only polymerase chain reaction (PCR)-tested individuals were included. COVID-19 cases (PCR-positive individuals) and controls (PCR-negative) identified between December 23, 2021, and February 21, 2022, were matched in a 1:1 ratio based on sex, nationality, and calendar week of PCR testing. However, a 1:5 matching ratio was used to estimate effectiveness against severe, critical, or fatal cases to improve statistical precision.

Reinfection was defined as infection occurring after at least 90 days of previously documented infection. Double and triple vaccinated participants who received messenger ribonucleic acid (mRNA) vaccines only (BNT162b2 or mRNA-1273) were included in the study. Those who received heterologous vaccine doses were excluded.

They categorized the study population as 1) SARS-CoV-2-naïve and double-vaccinated, 2) double-vaccinated with previous infection, 3) infection-naïve and triple-vaccinated, 4) triple-vaccinated with prior infection history, and 5) non-vaccinated, infected. Odds ratios and associated 95% confidence intervals (CIs) were computed using conditional logistic regression.


During the study period, there were 1.3 million double-vaccinated individuals and 341,438 boosted participants. The median interval between the first and second dose and second and booster dose was 21 and 251 days, respectively. The study population was predominantly male and young. Of the 315 PCR-positive samples randomly selected for whole-genome sequencing, 300 were Omicron infections, and 15 were Delta infections. Most Omicron cases (76.2%) were BA.2 infections.

The researchers found that the effectiveness of prior disease in non-vaccinated participants was 50.2% against symptomatic infection with BA.1 variant. The efficacy of two doses of BNT162b2 in the infection-naïve population was negligible. Triple vaccination in those without prior infection showed 59.6% efficacy. In double vaccinated subjects with the previous disease, efficacy was 51.7%, and in previously infected subjects who received three BNT162b2 doses, a 74.4% efficacy was observed.  High efficacy (>90%) was evident across all five groups against severe, critical, and fatal COVID-19 due to Omicron BA.1 infection.

The authors noted 46.1% effectiveness among the previously-infected non-vaccinated participants against infection with BA.2 variant. Like with BA.1, efficacy against BA.2 infection was negligible among double-vaccinated infection-naïve subjects. Efficacy was 52.2% in boosted, SARS-CoV-2-naïve participants.

Double vaccination with the BNT162b2 vaccine in previously infected individuals was 55.1% effective against BA.2 infection. Effectiveness against BA.2 infection was the highest (77.3%) among previously infected people vaccinated with three BNT162b2 doses. Overall, the severity of Omicron BA.1 infections was low, with severe, critical, and fatal cases constituting 0.3% of the total (BA.1) infections. Similarly, just 0.3% of BA.2 infected patients were hospitalized or died. 


The study found that previous infection with the non-Omicron variant approximately reduced infection risk by 50%, with no profound differences between BA.1 and BA.2 subvariants. Notably, effectiveness against either subvariant was negligible for SARS-CoV-2-naïve double-vaccinated subjects. This could plausibly be explained by the declining immunity in vaccinated individuals, given that participants received their second dose eight months ago (or longer).

A third vaccine dose approximately reduced the risk of infection by 60%. The high efficacy might be because most individuals received the booster 45 days before inclusion in the study. Interestingly, the protection conferred by hybrid immunity in double-vaccinated subjects was similar to the immunity induced by infection alone. Boosted individuals with a history of COVID-19 were the most protected. There were no pronounced differences among the recipients of BNT162b2 and mRNA-1273 vaccines.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.


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