The COVID-19 infection caught the world unaware in late-2019. Very little was known about the condition, its clinical features, treatment, and long-term outcome. Though the Covid-19 pandemic has been ravaging the world for over 2 years now, our understanding of the disease is fast growing as the transmission of SARS-CoV-2 continues around the world. This is due to the unrelenting, concerted efforts by the global science community to unravel the mysteries of the infection. Although most COVID-19 patients get well within a few weeks of the onset of symptoms, some suffer from residual symptoms that continue for several months. This is especially true for people with long covid (a covid-19 infection that did not resolve in a few weeks). Concerns have been raised concerning the long-term complications of COVID-19 following reports of cardiovascular, pulmonary, and neurological disorders amongst people who had covid in communities with high infection prevalence.

In the COVID-19 pandemic, it has also become apparent that patients with cancer are more sensitive to SARS-CoV-2 infection and have a higher probability of developing severe COVID-19 than the general population. This is collaborated by many studies linking severe COVID-19 illness

The Interplay between SARS-CoV-2 and Cancer Biology: (A) SARS-CoV-2 internalization. (B) Immune interactions. (C) Arterial and venous thrombotic events

to an immunosuppressive state seen in cancer and other immunocompromised conditions. Even though there is no definitive substantiation to prove that long-term COVID-19 exposure raises the susceptibility to cancer in people who have never had cancer. There is an increasing in-flux of reports that exposure to the COVID-19 infection for an extended period may predispose patients to cancer and expedite its progression in patients with early-stage malignancies. Recent studies show that SARS-CoV-2 can modulate oncogenic pathways, sustain persistent low-grade inflammation, and cause tissue damage. All of these provide the ideal milieu for the development of cancer. More research is critically needed to understand the effects of extended COVID-19 on cancer risk. Let us explore what is known about Covid19 and its association with cancer development and progression in this article.

How Does Covid-19 Increase The Risk For Cancer Development

Many viruses are known to cause cancer or increase the risk of developing malignancies. Viruses like Epstein Barr virus and Hepatitis viruses are well-studied for their effects on cancer development. Research shows many of the processes leading to oncogenesis caused by these viruses is true for COVID-19. Now, let’s look at approaches by which COVID-19 can increase the risk for cancer.

Chronic Inflammation

The COVID-19 infection causes a general inflammatory response in the body. This quickly subsides in people who recover completely from the illness in a few weeks. In contrast, there is a lingering inflammatory state for those who have persistent symptoms (Long-Covid). There is a continuous release of pro-inflammatory cytokines like TNF-alpha (tumor necrotic factor-alpha) and Interleukins, which cause tumorigenesis in this constant inflammatory state. In addition, low tissue oxygen levels caused by inflammation or viral-mediated adequacy of ACE-2 (angiotensin-converting enzyme2) can result in oxidative stress and carcinogenesis. With time, persistent inflammation and oxidative stress can lead to DNA damage and subsequent cancer development. Furthermore, it is noteworthy that the multiple organ injury caused by the Covid-19 infection creates a suitable environment for tumor generation.

Hyperinflammation in COVID-19 and cancer occurs due to a cascade of events, including the activation of transcription factors, the production of inflammatory enzymes, and the release of eicosanoids and pro-inflammatory cytokines. These mediators enhance ongoing inflammation, contributing to disease progression and tissue destruction. SPMs, including resolvins, protectins, lipoxins, and maresins, exert their pro-resolving and anti-inflammatory effects by stimulating clearance of noxious stimuli (phagocytosis of SARS-CoV-2 and phagocytosis/efferocytosis of cancer debris), countering the “cytokine storm,” and exhibiting anti-thrombotic properties.

Impaired Immunity

Studies have associated the Sars-Cov-2 virus with an impairment in immunity. This may be a sequela of the inflammation caused by the infection. Immunocompromised states are associated with a propensity for developing cancers because it hampers the ability of the immune system to expunge potential carcinogenic cells. Research shows that Covid-19 causes T-cell depletion and activation of carcinogenic pathways such as MAPK, JAK-STAT, and NF-B, which may increase the risk of cancer formation in some people.

Disruption of the Cell Cycle

Cancers generally result when there is uncontrolled cell growth. This happens when cells gain the ability to initiate their development limitlessly and resist signals from genes trying to restrict unchecked growth. Genes responsible for this unrestricted growth are called oncogenes. Some viruses alter the cell cycle for their replication. This causes the expression of many oncogenes, which are genes that promote cancer. So, certain viruses may have an impact on cancer risk. Recent studies show that the Covid-19 virus interacts with 96 oncogenes. It means that Covid-19 has a potential effect on cancer-related pathways, including; impacting cell proliferation, promoting DNA degradation, and delaying the repair of damaged cells. Research on the SARS coronavirus, which is very similar to SARS-CoV-2, suggests that there could be a link between SARS-CoV-2 and carcinogenesis. Nonstructural protein 3 (Nsp3) has been linked to the destruction of the p53 protein, which is a protein that helps fight cancer. The SARS-CoV endoribonuclease Nsp15 also interacts with the retinoblastoma tumor suppressor protein (pRB), which allows it to be degraded by the ubiquitin-proteasome pathway, predisposing cells to uncontrolled growth and subsequent cancer development. Furthermore, studies have established a connection between the S2 subunit of SARS-CoV-2 and the p53 and BRCA1/2 proteins. Genomic instability and abnormal cell development can result from the absence of these cellular guardians and gatekeepers.

Final Consideration

While many studies have linked COVID-19 to an increase in cancer risk. These reports are not conclusive. Cancer development is seldom the result of a single mutagenic event; instead, it results from a series of tumorigenic events accumulated over a lengthy time. Although SARS-CoV-2 is not a classic oncovirus because it does not integrate into the host genome, the virus may produce an oncogenic environment by inducing the host’s immune system. So, it is conceivable that COVID-19, when combined with other mutagenic events, could predispose the body to cancer development and expedite the progression of existing cancers. Given the rapidly increasing number of SARS-CoV-2-infected persons worldwide, getting conclusive evidence on the long-term consequences of COVID-19 infection (especially the possibility of cancer development) through well-planned, long-term clinical research is critical.

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