**Abstract**

The COVID-19 pandemic has affected more than 125 million lives worldwide and more than 2.5 million people have died so far. Cancer in itself increases the risk of infection especially, cancer patients undergoing cancer-associated treatments are more susceptible to SARS-CoV2 infection. However, many questions related to the biological interconnection between the two diseases remain to be answered. This chapter summarizes some of the biological components that connect cancer to COVID-19 and provide knowledge to not only understand but also, target the co-morbidities.

**Keywords:** COVID-19, cancer, viral infections, chemotherapy, radiotherapy, immunotherapy, cytokine storm, coagulopathy, ACE2, TMPRSS2

### **1. Introduction**

For past many decades, viral infections have presented a great challenge for cancer patients, on the delivery of cancer care, cancer research, and oncologists. COVID-19 caused by SARS-CoV2 virus continues to spread around the globe and more than 1 million people have been killed due to COVID-19 worldwide (at the time of writing). Though majority of infected people will recover, cancer patients remain at a higher risk to SARS-CoV2 infection and its related severe outcomes. Cancer patients are reported ~3 times more susceptible to SARS-CoV2 infection with possible poor outcomes than individuals without cancer potentially due to their systemic immunosuppressive state caused either by malignancy itself or the anti-cancer treatments. Moreover, the mortality rate of SARS-CoV2 positive cancer patients was reported 6% than 1% for non-cancer patients in China. However, a limited research has been done to understand the biological interconnection between cancer and viral infections. Especially, little is known about the SARS-CoV2 infection biology Therefore, studying whether and how SARS-CoV2 affects cancer and its progression and, vice versa is of utmost importance for (1) the better management of SARS-CoV2 infected cancer patients and, (2) developing novel treatment strategies that can target SARS-CoV2 and/or cancer.

#### **2. Linking viruses and cancer**

Viruses are the smallest microorganisms made up of a small number of genes in the form of DNA or RNA surrounded by a protein coating. Viruses enter into a living cell and hijack it's cellular machinery in order to make more copies of itself. When a virus enters the body, it triggers the body's immune system. These immune defenses begin with white blood cells which learn to attack and destroy the virus or the virus infected cells. If the body survives the virus attack, the immune system's memory is able to respond more quickly and effectively to subsequent infection by the same virus. This response is called Immunity. Immunity can also be triggered by getting a vaccine. Viruses can be divided into three classes: oncogenic, oncolytic and, non-oncogenic non-oncolytic viruses. The oncogenic viruses (for example, hepatitis C virus, human T-lymphotropic virus, hepatitis B virus) change cells by either integrating their genetic material with the host cell's DNA or enhancing already existing oncogenic genes within the host genome. Thus, the infected cell is regulated by the viral genes and has the ability to undergo abnormal growth. Conflicting results for the relationship between different viruses and various cancer sub-types have been stated in pre-clinical and clinical settings. This is due to the reason that the course and outcome for both, viral infections and cancer and regulated by the type of viral infection, type of cancer and the immune system components involved. For example, a faster growth of melanoma was observed in mice that were challenged with H1N1/influenza A virus due to shunting or diversion of cytotoxic T cells from tumor site to the viral infection site. On the contrary, a slower growth of Lewis lung carcinoma cells was observed in mice following influenza virus infection. Thus, more studies need to be undertaken for clearer context dependent results. Both viruses and cancer invade our normal healthy systems for their growth and proliferation. The inability of our immune system to distinguish between self and non-self, links the severe pathogenesis associated with cancer and viral infections.
