Coronavirus and Cancer—is There a Link?

Authored by:  Venkat Rao

Is coronavirus disease linked to cancer? Most known symptoms of COVID-19, generally short-term in nature, are mild to moderate resembling common cold and flu such as cough, nasal congestion, shortness of breath, sore throat, and fever with respiratory system as the primary target. However, the link between COVID-19 and cancer is far more insidious and worrisome than how we understand cause-effect relationship between cancer-inducing agents and the formation of cancer.

A recent study, published in the Journal of the American Medical Association Network found an association between COVID-19 and increased diagnosis of high-risk gastrointestinal (HRGI) stage 4 cancers.

The investigation did not find a causal link between SARS-CoV-2 virus and higher incidence of cancer. The reported association between coronavirus and cancer was not causative but due to underdiagnosis of patients with HGRI during the pandemic. The study did not find any change in 1-year survival or operative mortality among patients with HRGI stage 4 cancer, indicating a greater incidence was due to underdiagnosis during the pandemic for patients with certain malignant neoplasms, such as HRGI stage 4 cancers. Simply put, the reported surge in certain types of deadly cancer incidence is linked to social constraints, such as social distancing that were put in place to control the spread of COVID-19, limiting external activities, causing great stress and anxiety of uncertainty due to unpredictable and unknown aspects of the pandemic resulting in sudden drastic changes in the daily lives and activities of people and family.

The study evaluated the effect of disruptions caused by the pandemic on the treatment and outcomes among patients with HGRI cancers, and specifically on patient survival and long-term treatment outcomes. Using a cohort study design, a total of 156,937 patient data from the National Cancer Database with HRGI cancer (esophageal, gastric, primary liver, or pancreatic) were diagnosed between January 2018 and December 2020. The study found a substantial decrease in the number of new cases during the pandemic period, which returned to pre-pandemic levels after July 2020. The decrease in new cancer cases was primarily due to the lower number of patient screening and diagnosis. The raw numbers lowering new cases detection was because fewer patients with serious cancer conditions showed up at the hospital for treatment. COVID-19-induced sequestration was considered the main reason for the increase in stage IV disease observed for HRGI cancers during the pandemic. In a peculiar way, COVID-19 pandemic is associated with increased diagnosis of stage 4 HRGI cancers not because SARS-CoV-2 virus is a causative agent for cancer but due to underdiagnosis of patients with high-risk cancers.

Adverse impact of COVID-19 pandemic on serious cancer patients is extremely complex with the virus seemingly play no direct role as the causative agent for carcinogenesis, but had more to do with pandemic-related stressors resulting in patients with cancer experiencing worse outcomes during the pandemic. In the study, 187 adult patients with cancer diagnosis participated in an online survey. The stress scores for study participants exceeded the established benchmarks for oncology patients and was at levels comparable to noncancer patients with post-traumatic stress disorder among study participants in the highly stressed group reporting a high percent occurrence rate for depression (71%), anxiety (78%), sleep disturbance (78%) and cognitive impairment (92%). The extremely high rates of stress together with the psychological symptoms among patients with cancer was way above the established benchmark and comparable to stressors associated with post-traumatic stress disorder.

There are no parallels in public health where a significant increase in disease burden of cancer increased not due to exposure to cancer initiators such as carcinogenic chemicals, toxins, radiation, and viruses. Instead, COVID-19 presented an entirely diverse set of external factors, not related to coronavirus resulting in higher levels of stage 4 HRGI cancer diagnosis attributed to underdiagnosis during the pandemic. Although no published data is yet available, it is safe to assume other serious types of cancer and life-threating diseases were similarly impacted during the pandemic, the scope of which remains unknown at present.

The narrative thus far begs the question: Is SARS-CoV-2 a cancer-causing virus?

Much of what is known about SARS-CoV-2, the virus, and COVID-19, the disease, are adverse impact in the short-term, whereas virus and chemical induced cancers are a long-term hazard requiring many years of a cancer-initiated state requiring additional triggers to a full-blown cancer. We are still in the initial stages of a massive global exposure to the virus with extremely limited information on the potential long-term impact of SARS-CoV-2 as an oncogenic virus. Experimental studies thus far demonstrate the virus’s ability to induce re-infection/reactivation and persistent infections resembling exposure to oncogenic virus, which is the most worrying aspect of the potential long-term effects likely to be reported in the coming decades from all over the world.

SARS-CoV-2 virus induces a pattern of inflammatory response in the host triggered by cell cycle regulation and signaling pathways linked to oncogenic virus induced cancer in both experimental animals and humans.

Viruses are well-known for causing cancer in humans. Researchers seeking to explore whether SARS-CoV-2 is an oncogenic virus are on a sound line of investigation. Given the global nature of the COVID-19 pandemic with billions of human beings exposed to the virus, almost every type of cancer, including the rare types are likely to show up in the global population in the coming years and decades. Viruses such as human papillomavirus, hepatitis B and C viruses, Epstein-Barr virus are few well known examples of oncogenic viruses known to promote initiation and formation of cancer in humans.

Published research reports seem to indicate that SARS-CoV-2 coronavirus may create a physiological condition in COVID-19 recovered patients a predisposition to the onset of cancer and cancer development. These reports suggest the SARS-CoV-2 ability to trigger chronic, low-grade inflammation resulting in sustained tissue damage creates the condition for initiation of cancer. The risk of sustained inflammation is typical among patients with long COVID-19 disease. An estimated

49 percent of individuals contracting COVID-19 experience persistent symptoms of the disease, making the potential cancer-causing risk a serious global public health disease burden in the coming decades.

Is SARS-CoV-2 link to cancer proven? We do not have sufficient information to make a conclusive statement. The rise in the incidence of stage 4 high-risk gastrointestinal cancer diagnosis during COVID-19 pandemic was a peculiar outcome mostly due to underdiagnosis of terminal cancer patients who could not follow-up on routine hospital visits for treatment due to social distancing and lock-down for extended periods.

However, a more serious long-term cancer risk lurks in the background, the contours of which remain unknown at present, and likely to unravel in the coming years and decades. Long terms risks of COVID-19 pandemic such as cancer places additional burdens in terms of treatment and life-long care of patients on the global public health systems.