COVID-19 Boosters Protect Immunocompromised People From Breakthrough Infections

New research findings provide solid evidence that annual COVID-19 vaccine booster doses continue to be advisable for certain immunocompromised people, researchers at McGill University say.

The researchers looked at how often people with immune-mediated inflammatory diseases (IMIDs) got COVID-19 despite having received at least three doses of an mRNA COVID-19 vaccine. IMIDs – including rheumatoid arthritis, lupus, inflammatory bowel disease and multiple sclerosis – affect more than seven million Canadians. The medications they take often weaken their vaccine responses, increasing their vulnerability to infection.

Published in Vaccines, the study found that 15 per cent of IMID patients contracted COVID-19 at least once during the year-long study, but that patients with higher levels of a specific antibody, which is produced in response to the vaccine, had lower chances of getting infected.

“Our findings highlight why booster doses are so important, because immunity naturally wanes over time, and maintaining those high antibody levels may be key to protecting against infection,” said senior author Sasha Bernatsky, James McGill Professor in McGill’s Divisions of Rheumatology and Clinical Epidemiology and a senior scientist at the Research Institute of the McGill University Health Centre.

Past COVID-19 infections did not clearly affect the risk of a breakthrough case in the study.

“This is an important takeaway for those who assume they have lasting immunity after contracting the virus,” Bernatsky said.

Data helps inform Canada’s vaccine guidance

The research team tracked 366 IMID patients across Canada, primarily in Quebec. Unlike previous studies that relied on self-reported infections or hospital data, this research used saliva PCR tests and antibody measurements, offering a more precise picture of infection risks.

Early in the pandemic, clinical vaccine trials rarely included immunocompromised patients, leaving a major gap in understanding how vaccines worked for this group. To address this, the Public Health Agency of Canada and the COVID-19 Immunity Task Force commissioned this in-depth study. The researchers say their findings have given Canada the solid evidence it needs to keep recommending annual booster shots, five years after the pandemic began.

“The first mRNA vaccines in 2021 were highly effective at preventing severe illness, but as immunity wanes and new variants emerge, breakthrough infections have become more common,” said Bernatsky. “COVID-19 remains a major cause of hospitalizations, especially for vulnerable groups. Much like influenza, it’s now a seasonal threat we can’t ignore.”

The research was a collaboration between McGill University, the Research Institute of the McGill University Health Centre (The Institute), the University of British Columbia, Université Laval, McMaster University, Mount Sinai Hospital, the University of Manitoba and Canadian Arthritis Patient Alliance.

Research on the effectiveness of newer vaccine strategies in IMID and other immunocompromised patients is now underway at The Institute, led by Ruth Sapir-Pichhadze, Inés Colmegna, Arielle Mendel, and other researchers.

Reference: Tan J, Bernatsky S, Lee JLF, et al. COVID-19 breakthrough infections in immune-mediated inflammatory diseases: data from the SUCCEED (Safety and Immunogenicity of COVID-19 Vaccines in Systemic Autoimmune-Mediated Inflammatory Diseases) study. Vaccines. 2025;13(2). doi: 10.3390/vaccines13020104

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