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. medRxiv.2023Sep8. doi: https://doi.org/10.1101/2023.08.24.23294503.

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A CITF-funded study, published in preprint and not yet peer-reviewed, provided evidence that individuals with hybrid immunity (a combination of infection-acquired and vaccine-induced SARS-CoV-2 immunity) had nearly 90% protection against severe outcomes (hospitalization or death) during the Omicron BA.1/BA.2 and BA.4/BA.5 predominant periods. However, this protection was reduced during the BQ/XBB predominant period. Nonetheless, each subsequent booster vaccine dose (up to five vaccine doses were studied), did increase protection against severe outcomes. 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%) against severe outcomes (hospitalization or death) during periods when Omicron subvariants BA.1/BA.2 predominated. However, protection was below 50% 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 PCR-confirmed prior SARS-CoV-2 infection and second, third, or fourth vaccine dose) 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 but this protection diminishes over time and 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 adults aged ≥50 years with one or more PCR tests for SARS-CoV-2 in Ontario between January 2, 2022, and June 30, 2023.