Prior infection and vaccination protect against severe consequences of SARS-CoV-2 infection Omicron

Prior infection and vaccination protect against severe consequences of SARS-CoV-2 infection Omicron

A new study published in The Journal of Infectious Diseases reports that prior infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and booster vaccination protect against intensive care unit (ICU) admission and mortality following infection with the SARS variant -CoV-2 Omicron. However, the scope of this protection is reduced against the Omicron variant compared to the Delta variant.

Study: Impact of Vaccination, Prior Infection and Treatment on Omicron Infection and Mortality. Image Credit: Chaikom /


As of December 1, 2022, nearly three years after the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, more than 648 million people have been infected with SARS-CoV-2 in the world, of which 6.6 million died.

Viral genomes undergo adaptive changes that alter their pathogenic potential. As with other ribonucleic acid (RNA) viruses, SARS-CoV-2 is susceptible to genetic evolution as it adapts to new human hosts.

This has resulted in the emergence of different viral variants with distinct properties from the original SARS-CoV-2 strain. To date, five major SARS-CoV-2 variants of concern (COV) have been identified, which include Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta ( B.1.617.2) and Omicron variants (B.1.1.529).

South Africa was the first country to identify the Omicron variant in late November 2021. Since then, this COV has spread rampantly around the world and has remained the dominant strain in circulation.

Omicron COV can evade immunity conferred by COVID-19 vaccines and infection by other SARS-CoV-2 variants. However, there is a lack of evidence specifying the extent to which decreased immunity from COVID-19 vaccines or prior infection with SARS-COV-2 against predicts serious outcomes related to Omicron infection. Additionally, few studies have discussed the effectiveness of monoclonal antibody therapy given after Omicron infection against severe outcomes in real-world settings.

Given these concerns, researchers in the United States conducted an extensive study examining the link between COVID-19 immunization and prior SARS-CoV-2 infection. In addition, the risk of severe disease caused by Delta and Omicron VOCs was also compared with respect to vaccination, prior infection, and monoclonal antibody statuses.

Delta variants were used in this study as controls to determine whether immunization, prior infection, and therapy protect against Omicron COV infection and its severe consequences, as well as the lethality of Omicron infections. .

About the study

In the current study, 295,691 people were tested for SARS-CoV-2 at the Cleveland Clinic between October 1, 2022 and January 31, 2022. A case-control study was used to independently assess the association between vaccination and prior infection with SARS-CoV-2 infection for predominant Delta and Omicron phases.

Six categories of vaccination status were identified, which included 14 to 179 days after the third dose of the messenger RNA (mRNA) vaccine (BNT162b2 or mRNA-1273), more than 180 days after the third dose of the mRNA vaccine, 14 to 179 days after the second dose of the mRNA vaccine; 180 days after the second dose of the mRNA vaccine; any other COVID-19 vaccinations; and unvaccinated.

Monoclonal antibodies against SARS-CoV-2 were given to people aged 18 and older who developed symptoms within seven days of testing positive for COVID-19. During the Delta and Omicron dominant periods, the Kaplan-Meier curve was used to assess and compare the survival probability of patients who tested positive for COVID-19.

The researchers used logistic regression and Cox analyzes to assess whether vaccination, prior infection, and/or monoclonal antibody therapy correlate with the risks of prolonged hospitalization and death in ICUs.

Prior infection conferred limited protection against the Omicron variant

Over time, there was a significant decrease in the effectiveness of the two- and three-dose vaccination series. Both vaccine regimens were significantly less effective against Omicron than Delta VOC.

Delta VOC infection has been associated with a third dose of vaccination taken less than 180 days ago, compared to unvaccinated people. Comparatively, infection with the Omicron variant was associated with taking the second vaccination dose more than 180 days before testing positive for COVID-19.

According to the estimated odds ratios of infection with Delta and Omicron variants, prior infection with SARS-CoV-2 offered less protection against Omicron COV than Delta COV.

The delta variant causes more severe disease than Omicron

During the Omicron-dominated period, Kaplan-Meier estimates of survival probabilities were significantly higher than those of the Delta-dominated period. The 28-day mortality rates were 1% and 1.80%, respectively, and the hazard ratio of death due to infection with Omicron versus Delta was 0.60.

Moreover, the survival curves between the two periods were significantly closer and the hazard ratio decreased from 0.63 to 0.83. This demonstrates that the Omicron VOC precipitates less severe results than the Delta VOC.

Vaccination and prior infection reduce risk of ICU hospitalization and death from Omicron infection

During the Omicron-dominant period, the effectiveness of two doses of mRNA vaccine in preventing death declined over time. However, receiving the two- or three-dose series of vaccinations within the previous six months significantly reduced the risk of death from Omicron infection.

The 95% confidence intervals for the hazard ratios for death of the Delta and Omicron variants were 0.43 and 0.28, respectively, when vaccination was given within 180 days of infection. Delta and Omicron infections in people with a history of COVID-19 were expected to have a risk of death ratio of 0.22 and 0.47, respectively.

For Delta and Omicron VOCs, the relative risk associated with prior infection was 0.04 and 0.27, respectively. With respect to mortality rate, the association with hospitalization was weaker, while that with ICU admissions was comparable.


Vaccination and prior infection appear to be less protective against infection with the Omicron variant than the Delta variant. Nevertheless, these factors reduce the likelihood of intensive care hospitalizations and death from Omicron infection.

A significant increase in the effectiveness of two doses of mRNA vaccine against infection, ICU admission, and death was notable after receiving a third dose of booster vaccine; however, the effectiveness of these vaccine doses has decreased significantly over time. Additionally, monoclonal antibody therapy given after Omicron infection significantly reduced the likelihood of ICU admissions and mortality.

The relatively low mortality posed by Omicron compared to Delta VOC can be attributed to both the reduced lethality of the Omicron variant and the improved acquired immunity among populations who have received booster vaccinations and who have already been infected with SARS-CoV-2.

According to the study results, a second dose of vaccine given more than 180 days before infection provides minimal protection against the Omicron variant. This is likely because the Omicron spike (S) protein can evade neutralizing antibodies generated by two doses of mRNA vaccine. Similarly, prior SARS-CoV-2 infection confers less protection against the Omicron variant compared to the Delta variant.

Journal reference:

  • Wang, X., Zein, J., Ji, X., et al. (2022). Impact of Vaccination, Prior Infection and Treatment on Omicron Infection and Mortality. The Journal of Infectious Diseases. doi:10.1093/infdis/jiac460

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