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

Publication date: Jul 11, 2025

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.

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Concepts Keywords
Basel colorectal cancer
Cancer COVID-19
Diabetes herpes zoster

Semantics

Type Source Name
disease MESH Colorectal Cancer
pathway KEGG Colorectal cancer
disease MESH Herpes Zoster
disease MESH COVID-19
disease MESH complications
disease MESH infections cardiovascular
disease MESH cancer
disease MESH respiratory failure
disease MESH sepsis
disease MESH chronic kidney disease
disease MESH hypertension
drug DRUGBANK Coenzyme M
pathway REACTOME Immune System
disease MESH heart disease
disease MESH infections
disease IDO cell
disease MESH cardiovascular disease
disease IDO infection
disease MESH causality
disease MESH inflammation
disease MESH T cell exhaustion
disease MESH viral infections
disease MESH retinoblastoma
disease MESH carcinogenesis
disease MESH Co infection
disease MESH superinfection
pathway KEGG Viral replication
disease MESH death
disease MESH cardiac arrest
disease MESH cardiac arrhythmias
disease MESH heart failure
disease MESH intracerebral hemorrhage
disease MESH cerebral infarction
disease MESH ischemic heart diseases
disease IDO algorithm
disease MESH diabetes mellitus
disease MESH clinical relevance
disease IDO susceptibility
drug DRUGBANK Isoxaflutole

Original Article

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