Study Investigates Optimal COVID-19 Vaccination Timing in Inflammatory Disease


Most (94%) anti-nucleocapsid positivity was linked to a self-reported COVID-19 infection within the prior 3 months.

Study Investigates Optimal COVID-19 Vaccination Timing in Inflammatory Diseases

Dawn Bowdish, PhD

Credit: McMaster University

A Canadian study examined how serologic responses to COVID-19 vaccination and infection are affected by time since last vaccination, among other factors, in a cohort of patients with immune-mediated inflammatory disease (IMID).

Results indicated positive associations for log-transformed Receptor Binding Domain (anti-RBD) titers were linked to the number of doses, self-reported COVID-19 infection, and female sex, while negative associations were seen with prednisone and rituximab use, according to research published in The Journal of Rheumatology.1

Between 2022 and 2023, 4 times as many people in the US were hospitalized for COVID-19 compared with influenza. Currently, the COVID-19 mortality risk is double that of influenza.2 Further, patients with IMID may be unsure about the potential benefits of additional booster vaccinations, and this hesitancy could potentially put these patients at a higher risk for infection.

“Vaccine hesitancy in general is a huge problem, particularly for people with IMID,” wrote a team of investigators led by Dawn Bowdish, PhD, associate professor at McMaster University and a Canada Research Chair in Aging & Immunity. “As the necessity for multiple COVID vaccine doses became clear, social ‘vaccine fatigue’ has caused many individuals to decline additional COVID boosters after the primary series. Since COVID-19 infection is a potentially fatal and vaccine-preventable co-morbidity, it is vital that individuals with IMID have access to relevant information that will help them decide when to get their next COVID vaccination.”

Dried blood spots/sera and other data were obtained from adults with rheumatoid arthritis (RA), systemic lupus, psoriasis and psoriatic arthritis (PsA), ankylosing spondylitis and spondyloarthritis, and inflammatory bowel disease post-vaccination. The first sample was collected at enrollment and again at 2—4 weeks, 3 months, 6 months, and 12 months post-vaccine. The serologic response was determined using multivariate generalized estimating equation regressions, such as medication use, vaccination history, and demographics.

Among the cohort, 64.7% patients were female, the mean age was 53.2 years, and 88.4% were white. The most common inflammatory condition was inflammatory bowel disease followed by RA.

In patients with IMID, positive associations for log-transformed anti-RBD titers were shown in self-reported COVID-19 infections between 2021 and 2023, female sex, and number of vaccinations. Negative associations were demonstrated in patients who received prednisone, rituximab, and tumor necrosis factor (TNF) inhibitors.

Most (94%) anti-nucleocapsid positivity was linked to a self-reported COVID-19 infection within the prior 3 months. Between March 2021 and February 2022, 5—15% of samples exhibited anti-nucleocapsid positivity. This positivity increased to 30—35% or higher in the post-Omicron era (March 2023). The anti-nucleocapsid positivity among patients with IMID was lower when compared with Canada’s general population seroprevalence (> 50% in 2022 and > 75% in 2023.

Negative associations with log-transformed anti-RBD titers were seen in the time since last vaccination, especially after 210 days.

Investigators noted the comprehensive inclusion of factors related to serologic COVID-19 vaccine response among a large cohort of patients with IMID strengthened the study. However, the lack of detailed drug exposure information hindered their ability to determine certain issues, including if a patient received a particular drug in the week prior- or post-vaccination. Additionally, they were unable to evaluate interactions between drugs, IMID type, or vaccination type and its impact on COVID-19 infection.

“Ensuring adequate vaccination against SARS-CoV-2 in IMID can be difficult,” investigators concluded. “If individuals have access to relevant information that will help them decide when to get their next COVID vaccine, they may be more open to receiving additional doses. We believe that our findings will help patients, clinicians, and other stakeholders make personalized vaccination decisions, including consideration of additional doses when more than 6 months has elapsed since last COVID vaccination/infection.”


  1. Bowdish DME, Chandran V, Hitchon CA, et al. When Should I Get My Next COVID Vaccine? Data from the SUrveillance of responses to COVID-19 vaCcines in systEmic immunE mediated inflammatory Diseases (SUCCEED)study. J Rheumatol. Published online April 15, 2024. doi:10.3899/jrheum.2023-1214
  2. Xie Y, Choi T, Al-Aly Z. Risk of Death in Patients Hospitalized for COVID-19 vs Seasonal Influenza in Fall-Winter 2022-2023. JAMA. 2023 May 16;329:1697-99.
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