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

## TL;DR

People who get shingles after recovering from COVID-19 face higher long-term health risks, including a greater chance of colorectal cancer, suggesting a need for closer monitoring.

## Contribution

This study is the first to link post-COVID shingles with increased colorectal cancer risk using a large global health database.

## Key findings

- Post-COVID shingles patients had significantly higher risks of cardiovascular events, respiratory failure, sepsis, and colorectal cancer.
- Age ≥50, chronic kidney disease, diabetes, and hypertension were strong independent risk factors across outcomes.
- Cancer-free survival was significantly better in patients without post-COVID shingles.

## Abstract

COVID-19 can weaken the body’s immune system, allowing dormant viruses like the one that causes shingles to become active again. This study investigated whether people who developed shingles after recovering from COVID-19 were more likely to face serious long-term health issues, including heart disease, infections, and colorectal cancer. Using a large international health database, we analyzed tens of thousands of patients and found that those with shingles after COVID-19 had significantly higher health risks. These findings suggest that shingles could be a warning sign of lingering immune problems. Doctors should consider closer monitoring and earlier cancer screening for this group to improve long-term health outcomes.

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.