COVID-19 and Glioblastoma Onset

Medical News: The global COVID-19 pandemic has spurred extensive research into the wide-ranging effects of SARS-CoV-2, the virus responsible for the disease. While the respiratory manifestations of COVID-19 are well known, increasing attention is being directed toward its neurological complications. Some emerging hypotheses suggest that the intense inflammatory response and neurotropic characteristics of SARS-CoV-2 might create conditions that could, in theory, influence oncogenic processes in the brain, including the development of glioblastoma. This Thailand Medical News report focusses on our own review of current evidence and theories, drawing on published studies, while emphasizing that a direct causal link between COVID-19 and new onset glioblastoma remains an area of active investigation.


COVID-19 and Glioblastoma Onset

COVID-19 and Its Neurological Impact
Since the early stages of the pandemic, numerous studies have documented the neurological manifestations of COVID-19. Symptoms ranging from headaches and anosmia to more severe complications such as encephalitis, cerebrovascular events, and demyelinating syndromes have been reported. For instance, Ellul et al. (2020) described various neurological associations of COVID-19, noting that the virus can affect the central nervous system (CNS) either directly or indirectly through immune-mediated pathways. The neuroinvasive potential of SARS-CoV-2 raises questions about its long-term impact on brain health and the potential to trigger or accelerate pathological processes, including oncogenesis.
 
The Inflammatory Microenvironment and Glioblastoma
Glioblastoma is an aggressive form of brain cancer characterized by rapid proliferation and resistance to conventional therapies. A significant body of research has established that chronic inflammation and an immunosuppressive tumor microenvironment play critical roles in the development and progression of glioblastoma. Studies have shown that pro-inflammatory cytokines, growth factors, and immune cell infiltration can create a milieu conducive to tumor growth.
 
SARS-CoV-2 infection is known to trigger a robust immune response, sometimes resulting in a "cytokine storm." Elevated levels of interleukins (e.g., IL-6), tumor necrosis factor-alpha (TNF-α), and other inflammatory mediators have been observed in severe cases of COVID-19 (Mehta et al., 2020). In theory, such a hyperinflammatory state, particularly if sustained or inadequately resolved, might alter the CNS microenvironment in ways that could promote oncogenic transformation in susceptible cells. Although this mechanistic link is speculative at this stage, it provides a rationale for exploring whether SARS-CoV-2 could contribute to conditions favoring glioblastoma onset.
 
A Polish study in 2023 also indicated that COVID-19 infections set about the perfect environment for the development and onset of various cancers including brain cancers.
al-risk-factor-for-the-development-of-cancer">https://www.thailandmedical.news/news/breaking-covid-19-news-polish-review-study-shows-that-sars-cov-2-infections-are-a-potential-risk-factor-for-the-development-of-cancer
 
It has been found that the SARS-CoV-2 virus also uses the Neuropilin-1 (NRP1) proteins as receptors for viral entry as in doing so, causes the upregulation of these NRP-1 proteins which are also associated with increasing the risk of cancer.
https://www.thailandmedical.news/news/sars-cov-2-and-cancer-increased-neuropilin-1-expression-as-a-result-of-covid-19-can-lead-to-progression-of-primary-brain-tumors-besides-neurological-i
 
Studies and cases reports have already showed that COVID-19 hospitalizations are linked to the elevated risk of developing aggressive brain cancers.
https://www.thailandmedical.news/news/breaking-covid-19-news-study-finds-that-covid-19-hospitalization-linked-to-elevated-glioblastoma-risk-a-type-of-aggressive-brain-cancer
 
A recent study from researchers Texas MD Anderson has also found that COVID-19 infections accelerate the progressions of brain tumors and are also possibly responsible for the onset of glioblastoma.
https://www.thailandmedical.news/news/breaking-texas-md-anderson-study-finds-that-covid-19-accelerates-brain-tumor-progression-and-possibly-causes-new-onset-glioblastomas
 
Potential Mechanisms Linking SARS-CoV-2 to Glioblastoma
Several mechanisms have been proposed to explain how COVID-19 might influence glioblastoma risk:
 
Neuroinflammation and Immune Dysregulation:
SARS-CoV-2 can induce widespread neuroinflammation. Chronic inflammation is a known risk factor for various cancers, and persistent activation of immune pathways in the brain may lead to DNA damage, promote cellular proliferation, and impair apoptosis - processes that are implicated in tumorigenesis.
 
Disruption of the Blood-Brain Barrier (BBB):
Infection with SARS-CoV-2 has been associated with disruption of the BBB. A compromised BBB not only facilitates the entry of inflammatory cells and mediators into the brain parenchyma but also might allow oncogenic factors to interact with neural stem cells or other susceptible cell populations.
 
Molecular Mimicry and Viral Oncoproteins:
While many oncogenic viruses express proteins that directly interfere with cell cycle regulation, there is no definitive evidence that SARS-CoV-2 encodes such oncoproteins. However, molecular mimicry and aberrant immune responses triggered by the virus could potentially activate oncogenic pathways in neural tissues.
 
Hypoxia and Metabolic Stress:
COVID-19 often leads to systemic hypoxia. In the brain, hypoxic conditions can activate hypoxia-inducible factors (HIFs) that are implicated in tumorigenesis. These factors may contribute to an environment that favors the emergence or growth of malignant cells.
 
Epidemiological and Clinical Observations
At present, epidemiological data directly linking COVID-19 infection to an increased incidence of glioblastoma are limited. Most available evidence comes from case reports and retrospective analyses examining neurological complications in COVID-19 survivors. For example, some studies have noted unusual presentations of brain lesions and inflammatory changes in post-COVID-19 patients, although these findings do not confirm a causal relationship with glioblastoma development. The latency period for tumor development further complicates efforts to establish a direct link, as glioblastoma can take months or even years to become clinically apparent.
 
Limitations and Future Directions
It is important to emphasize that the hypothesis of COVID-19 increasing the risk of new onset glioblastoma is still in its infancy. Key limitations include:
 
-Lack of Long-Term Data: Given the relatively recent emergence of COVID-19, long-term studies are needed to assess whether survivors develop glioblastoma at rates higher than the general population.
 
-Confounding Factors: Many factors, including genetic predisposition and environmental influences, contribute to glioblastoma risk. Isolating the impact of SARS-CoV-2 amidst these variables is challenging.
 
-Mechanistic Uncertainty: While the inflammatory and immunological changes induced by COVID-19 provide a theoretical basis for increased cancer risk, definitive mechanistic studies are required to validate these links.
 
Future research should focus on longitudinal studies of COVID-19 survivors, detailed molecular analyses of post-infection brain tissue, and the development of experimental models that can mimic the interplay between viral infection and tumorigenesis in the CNS.
 
Conclusion
The potential connection between COVID-19 infection and the development of glioblastoma is an emerging and intriguing area of research. Although current evidence is largely speculative and based on the known effects of SARS-CoV-2 on neuroinflammation and the BBB, it raises important questions about long-term neurological risks associated with the virus. Rigorous epidemiological studies and mechanistic research are essential to determine whether COVID-19 contributes to glioblastoma onset, or if the observed associations are coincidental. As our understanding of both COVID-19 and glioblastoma deepens, future investigations will be crucial in clarifying this potential link and guiding clinical practice.
 
Additional References:
 
Ellul, M. A., Benjamin, L., Singh, B., Lant, S., Michael, B. D., Easton, A., ... & Solomon, T. (2020). Neurological associations of COVID-19. Lancet Neurology, 19(9), 767-783. https://doi.org/10.1016/S1474-4422(20)30221-0
 
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet, 395(10229), 1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0
 
Quail, D. F., & Joyce, J. A. (2017). The Microenvironmental Landscape of Brain Tumors. Cancer Cell, 31(3), 326‑341.
https://doi.org/10.1016/j.ccell.2017.02.009
 
Weller, M., Wick, W., Aldape, K., Brada, M., Berger, M., Pfister, S. M., … & Stupp, R. (2015). Glioma. Nature Reviews Disease Primers, 1, 15017.
https://doi.org/10.1038/nrdp.2015.17
 
For more about COVID-19 induced Glioblastoma, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/sars-cov-2-and-anorectal-cancer
 
https://www.thailandmedical.news/news/polish-medical-researchers-warn-that-covid-19-is-triggering-thyroid-cancers
 
https://www.thailandmedical.news/news/breaking-study-finds-that-covid-19-accelerates-liver-cancer-growth-and-spread-via-exosomes-derived-from-syncytia
 
https://www.thailandmedical.news/news/researchers-warn-that-covid-19-may-contribute-to-the-development-of-thyroid-cancer