Malignancy Risk in Long COVID: a Guide for Patients and GPs

Dr Graham Exelby, September 2025

A simplified an condensed version of “Malignancy in the Post-COVID Terrain: A Systems Biology Perspective on Chronic Inflammation and Dormancy Awakening”, part of a Long COVID portfolio

Background

Long COVID is now recognised as a chronic, multisystem disorder with persistent immune activation, vascular dysfunction, hypoxia, and metabolic imbalance. These changes closely mirror known pathways that increase the risk of cancer. Emerging clinical evidence suggests a possible link between Long COVID and increased malignancy risk, especially in breast, colon, lung, and brain cancers.

Why Might Long COVID Increase Cancer Risk?

Chronic Inflammation and Hypoxia

Persistent inflammation and vascular dysfunction in Long COVID lead to tissue hypoxia. This activates:

• HIF-1α: promotes angiogenesis and tumour survival.

• STAT3 & NF-κB: drive immune suppression and cell proliferation.

Viral Reactivation and Immune Exhaustion

EBV, adenovirus, and others can reactivate, linked to cancers like lymphoma. Long COVID also reduces:

• NK and CD8+ T-cell function.

• Stress/PTSD further suppress immunity.

Dormant Tumour Cell Awakening

New studies (e.g., Nature, 2025) show COVID can reawaken dormant cancer cells, especially in lungs.This may explain cases of rapid relapses post-COVID in previously stable cancers.

Genetic and Epigenetic Factors

DNA variants can impair DNA repair, mitochondrial function, and immune regulation (e.g., MTHFR, PEMT, TLR4). When combined with chronic inflammation, cancer-driving changes are more likely.

Environmental and Psychological Amplifiers

Toxins (e.g., mould, glyphosate) and PTSD drive inflammation and immune dysfunction via the same pathways, potentially amplifying cancer risk in predisposed individuals.

What Does the Clinical Data Show?

• UK Biobank & Flatiron Health: Higher cancer-specific mortality and metastasis risk post-COVID.

• SEER & NCI: More aggressive and late-stage tumours post-pandemic.

• Recent trials: Higher recurrence in breast and brain cancers after COVID.

Though delayed screening contributes, consistent global data suggest a biological effect.

Practical Implications for GPs

• Stay alert for early cancer signs in Long COVID patients.

• Watch for relapse in prior cancer cases.

• Extend follow-up and imaging where symptoms warrant.

• Educate patients on reducing toxin exposure and stress.

GPs are best placed for early detection in this potentially vulnerable population.

Key Mechanisms at a Glance (Simplified)

Pathway	Effect
Hypoxia → HIF-1α	Promotes blood vessel growth in tumours
STAT3 & NF-κB	Encourages cell growth and survival
Viral reactivation	Weakens immune defences
NK cell exhaustion	Reduces tumour surveillance
Genetic methylation defects	Increases DNA damage
Toxins & mould	Mimic or worsen inflammation
PTSD & stress	Amplify inflammation and immune suppression

Conclusion

Long COVID creates a potentially cancer-promoting state in genetically or environmentally susceptible patients. GPs play a central role in early detection, monitoring, and education. More research will clarify these associations, but proactive vigilance is key to protecting at-risk individuals.