Since the beginning of the pandemic, patients with inflammatory bowel diseases (IBD) have been considered at high-risk for infection and complications of COVID-19. However, IBD patients and patients taking immunosuppressive therapy were excluded from clinical phase III vaccine trials, complicating the assessment of effectiveness of these new vaccines. From past experience we know that adapted vaccination strategies may be appropriate in some IBD patients to optimize immunogenicity. We review current evidence on SARS-CoV-2 vaccination relevant to IBD patients, including immune responses from humoral to cellular, emerging data on new variants and off-label vaccination schemes. We also identify clinical and scientific knowledge gaps that can be translated into both large-scale population-based studies and targeted vaccine studies to describe the precise immune responses induced by SARS-CoV-2 vaccines in IBD patients. We strongly endorse the recommendation of vaccinating IBD patients to ensure maximal protection from COVID-19 both for the individual and the community.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an “original antigenic sin” type response.