Abstract
Background/Objectives: This study aimed to investigate the association between colorectal cancer (CRC) and the risk of breakthrough respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated patients with CRC. Methods: This retrospective cohort study used the TriNetX research network to identify vaccinated patients with CRC. Patients were matched using propensity score matching (PSM) and divided into patients with CRC and control (without history of CRC) groups. The primary outcome was the risk of breakthrough SARS-CoV-2 in vaccinated patients. The secondary outcome was a composite of all-cause emergency department (ED) visits, hospitalization, and death during the follow-up period after the diagnosis of COVID-19. Results: A total of 15,416 vaccinated patients with CRC were identified and propensity matched with 15,416 vaccinated patients without CRC. Patients with CRC had a significantly increased risk for breakthrough infections compared to patients without CRC (aOR = 1.78; [95% CI: 1.47-2.15]). Patients with CRC were at increased risk of breakthrough SARS-CoV-2 infections after two doses (aOR = 1.71; [95% CI: 1.42-2.06]) and three doses (aOR = 1.36; [95% CI: 1.09-1.69]) of SARS-CoV-2 vaccine. Vaccinated patients with CRC were at a lower risk of COVID-19 infection than unvaccinated CRC patients (aOR = 0.342; [95% CI: 0.289-0.404]). The overall composite outcome (all-cause ED visits, all-cause hospitalization, and all-cause death) was 51.6% for breakthrough infections, which was greater than 44.3% for propensity score-matched patients without CRC (aOR = 1.79; [95% CI: 1.29-2.47]). Conclusions: This cohort study showed significantly increased risks for breakthrough SARS-CoV-2 infection in vaccinated patients with CRC. Breakthrough SARS-CoV-2 infections in patients with CRC were associated with significant and substantial risks for hospitalizations.