Colorectal Cancer Risk Following Herpes Zoster Reactivation in COVID-19 Survivors: Global Multicenter Study Using...

COVID-19 has been linked to prolonged immune dysfunction and long-term health complications. Herpes zoster (HZ), a marker of impaired cell-mediated immunity, may signal increased vulnerability to infections, cardiovascular disease, and potentially cancer. However, its association with colorectal cancer (CRC) after COVID-19 has not been fully explored.

To investigate the long-term risks of cardiovascular events, acute respiratory failure, sepsis, and CRC in COVID-19 survivors who developed HZ compared to those who did not.

We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults diagnosed with COVID-19 between January 2020 and January 2022 were included. Among the full cohort (aged ≥18 years), 27,664 patients with post-COVID HZ were identified. Due to platform limitations, propensity score matching (PSM) was applied to a restricted subgroup of patients aged 55-60 years, yielding a 1:1 matched cohort for controlled comparisons. Outcomes were assessed over a three-year follow-up.

In the matched age-restricted cohort, patients with post-COVID HZ had significantly higher risks of cardiovascular events, acute respiratory failure, sepsis, and CRC compared to matched controls. Subgroup analyses identified age ≥ 50, chronic kidney disease, diabetes, and hypertension as strong independent risk factors across outcomes. Despite the low absolute CRC incidence, cancer-free survival significantly favored the non-HZ group.

Herpes zoster reactivation after COVID-19 is associated with increased risk of colorectal cancer. Enhanced surveillance and early CRC screening may benefit this high-risk population.