This is a summary, written by members of the CITF Secretariat, of:

Lee N, Nguyen L, Austin PC, Brown KA, Grewal R, Buchan SA, Nasreen S, Gubbay J, Schwartz KL, Tadrous M, Wilson K, Wilson SE, Kwong JC. Protection conferred by COVID-19 vaccination, prior SARS-CoV-2 infection, or hybrid immunity against Omicron-associated severe outcomes among community-dwelling adults. Clin Infect Dis. 2023 Nov 24:ciad716. doi:

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

A CITF-funded study, published in Clinical Infectious Diseases, provided evidence that protection provided by COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune evasive SARS-CoV-2 variants and subvariants emerge. Vaccine protection was high when Omicron BA.1/BA.2 was predominant but fell to less than 50% during periods of Omicron BA.4/BA.5 and BQ/XBB predominance. Hybrid immunity (a combination of vaccination and previous SARS-CoV-2 infection) conferred nearly 90% protection against severe outcomes (hospitalization or death) during the Omicron BA.1/BA.2 and BA.4/BA.5 predominant periods but was reduced and waned more quickly during the BQ/XBB predominant period. Protection was restored with a fifth vaccine dose. Prior infection alone did not confer lasting protection. This study was led by Dr. Jeffrey Kwong (University of Toronto).

Key findings:

  • Among individuals without documented prior infection, the primary two-dose COVID-19 vaccine series provided high protection (about 80% at six months) against severe outcomes (hospitalization or death) during periods when Omicron subvariants BA.1/BA.2 predominated. However, protection was below 50% at six months post-vaccine during periods of BA.4/BA.5 and BQ/XBB predominance without booster doses.
  • Protection from severe outcomes with a third dose (first booster) was 94% at six months post-vaccination during the BA.1/BA.2 predominant period but was only 59% during the BQ/XBB predominant period – and waned quickly over time. Protection did increase with each subsequent booster dose (a fourth or fifth dose).
  • Individuals with hybrid immunity (a combination of second, third, or fourth vaccine doses and previous PCR-confirmed SARS-CoV-2 infection) had approximately 90% protection against severe outcomes during BA.1/BA.2 and BA.4/BA.5 predominant periods. However, this protection was less than 75% during the BQ/XBB predominant period for all those who received a second, third, or fourth dose, and waned over time.
  • Individuals with hybrid immunity who received a fifth dose (bivalent) restored high protection against severe outcomes to 91% at six months during the BQ/XBB-predominant period.
  • Unvaccinated individuals with prior SARS-CoV-2 infection alone did not have lasting protection against severe outcomes. The protection from infection alone waned over time during the BA.4/BA.5 predominant period and even more so during the BQ/XBB predominant period.

COVID-19 vaccination and prior SARS-CoV-2 Infection provide protection against severe outcomes when individuals become infected again. But this protection diminishes over time and is markedly reduced as immune-evasive variants emerge. These findings support the need for a variant-adapted booster vaccination strategy with periodic review, even in populations with high vaccine coverage and prior infection prevalence.

This was a test-negative study designThe use of a control group with the same clinical presentation but testing negative for the pathogen of interest that included community-dwelling adults aged ≥50 years with one or more PCR tests for SARS-CoV-2 in Ontario between January 2, 2022, and June 30, 2023. Individuals who had received only one vaccine dose were excluded from the analysis.