A study by CITF-affiliated experts Drs. Andrew Costa (McMaster University) and Jeffrey Kwong (University of Toronto) assessed the extent of waning immunity among long-term care (LTC) residents in Ontario. They confirmed that vaccine effectiveness (VE) of a fourth dose of mRNA vaccine was highest within 84 days of the booster (50% against infection, 70% against symptomatic infection, and 80% against hospitalization or death). They also quantified the added effectiveness of a fourth dose compared to a third dose (received more than 84 days earlier), referred to as “marginal effectiveness”. They found that a fourth dose (received within 84 days of testing) was 23% more effective against infection, 36% more effective against symptomatic infection, and 37% more effective against hospitalization/death, compared to individuals who only received three doses. However, VE from the fourth dose waned significantly becoming negligible against infection by 112–139 days (3.5–4.5 months) and against hospitalization/death after 168 days (5.5 months) (2).

Vaccine effectiveness with hybrid immunity

Another study published in preprint, not yet peer-reviewed, looked at VE from a fourth dose, while accounting for hybrid immunity. CITF experts Drs. Gaston De Serres (Institut national de santé publique du Québec) and Danuta Skowronski (BC Centre for Disease Control) showed that hybrid immunity reduced the risk of hospitalization by at least 90% throughout the entire Omicron era and that the immunity acquired from the infection held the effects of additional vaccine doses stable. In other words, the protection conferred by hybrid immunity with a fourth dose was not significantly different from that with only three doses. Furthermore, when the infection originated from an Omicron subvariant, hybrid protection remained stable for at least eight months after the last immunological event (vaccine or infection) (3).

Both studies (Kwong/Costa and DeSerres/Sworonski) had a similar design: the first included LTC residents over 60 years of age who tested positive for SARS-CoV-2 in Ontario between December 2021 and August 2022; the second included symptomatic adults over 60 who tested positive for SARS-CoV-2 in Quebec between December 2021 and November 2022. Controls were those who tested negative. In both studies, the risk of COVID-related outcomes (infection, hospitalization, or death) was compared between individuals based on the number of doses received and/or their history of past infection.

The latest research on COVID-19 vaccine-induced immunity, therefore, shows that older individuals with a history of previous infection are well protected against severe COVID-19 disease, for a sustained period of time, and even for the latest circulating Omicron subvariants. As such, the research suggests that booster doses should include consideration of an individual’s history of SARS-CoV-2 infection. Priority should be given to those who have never been infected, which still represented half of the older Canadian population as of last fall.

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  1. Grewal R, Nguyen L, Buchan SA, Wilson SE, Costa AP, Kwong JC. Effectiveness and Duration of Protection of a Fourth Dose of COVID-19 mRNA Vaccine among Long-Term Care Residents in Ontario, Canada. The Journal of Infectious Diseases. 2022. DOI: 10.1093/infdis/jiac468
  2. Carazo S, Skowronski DM, Brisson M, Sauvageau C, Brousseau N, Fafard J, Gilca R, Talbot D, Ouakki M, Febriani Y, Deceuninck G, De Wals P, De Serres G. Prior infection- and/or vaccine-induced protection against Omicron BA.1, BA.2 and BA.4/BA.5-related hospitalisations in older adults: a test-negative case-control study in Quebec, Canada. medRxiv. 2022. DOI: 10.1101/2022.12.21.22283740