Which cancer type has the highest risk of COVID-19 infection?

Dear Editor,

Zheng Z. et al. [1] showed their data of the risk factors of critical and mortal COVID-19 cases, but the malignancy was excluded, which is unsolid. Different cancer types have diverse risk of COVID-19 infection, maybe this is the reason they didn't get the positive result. Cancer patients are one of the susceptible people, and the mortality rate is high [2].

Carly G. K. Ziegle et al. [3] have shown that Angiotensin-Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine 2 (TMPRSS2) are the receptors for SARS-CoV-2 to invade the human body, which are mainly located in the respiratory tract, lung, and intestines. But for cancer patients, not only are these organs at risk, but many tumor cells also express ACE2 and TMPRSS2.

Our pan-cancer analysis by using TIMER [4] showed that the expression levels of ACE2 in Esophageal carcinoma (ESCA), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), Uterine Corpus Endometrial Carcinoma (UCEC) are high. Similarly, TMPRSS2 levels in Kidney Chromophobe (KICH), Prostate Adenocarcinoma (PRAD), Uterine Corpus Endometrial Carcinoma (UCEC) are also increased; hence the risk of COVID-19 infection in patients with these tumors is higher. We also found that only UCEC is co-expressing ACE2 and TMPRSS2 receptors; therefore, patients with UCEC carry the highest risk of COVID-19 infection (Fig. 1 ).

Fig. 1

Which cancer type has the highest risk of COVID-19 infection? (A) The expression level of ACE2 in pan-cancer analysis. (B) The expression level of TMPRSS2 in pan-cancer. (C) The body map of the risk of COVID-19 infection in cancer. (Esophageal carcinoma (ESCA), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), Uterine Corpus Endometrial Carcinoma (UCEC), Kidney Chromophobe (KICH), Prostate adenocarcinoma (PRAD). P-value: 0 ≤ *** < 0.001 ≤ ** < 0.01 ≤ * < 0.05 ≤ . < 0.1)

If the SARS-CoV-2 virus infects the tumor cells, it will be difficult to clear due to the inherent immune resistance in the tumor microenvironment. Numerous studies have shown that the longer the virus stays in the body, the more tissues and organs will be damaged directly or indirectly [5]. Though many tissues will not be invaded by the virus, inflammatory reactions such as cytokine storms can cause tissue damage. Also, the cytokine storm caused by COVID-19, such as IL-6, may promote the progression of the tumor, such as UCEC [6].

Currently, COVID-19 treatment is mainly supportive care even though there is a debate on the use of ACE inhibitors (ACEi) or Angiotensin Receptor Blocker (ARB) as a treatment option. Mortality rates for patients with hypertension not taking an ACEi or ARB, taking an ACEi, and taking an ARB were 26.7%, 32.7%, and 30.6%, respectively [5]. Studies have shown that Bruton Kinase (BTK) Inhibitors can reduce inflammation reaction by blocking the Toll-like receptors signaling pathways, which is a good choice for patients with lymphoma [7]. Cytokines can promote tumor progression, indicating cytokine inhibitors, such as anti-IL-6 (Tocilizumab), may bring more benefits to cancer patients.

This letter is, to our knowledge, the first to determine the risk of COVID-19 for patients with cancer by a pan-cancer analysis about the expression level of ACE2 and TMPRSS2, and want to provide some advices for clinical physicians.

In conclusion, patients with UCEC are at the highest risk of COVID-19 infection. ESCA, KIRP, LUAD, KICH, and PRAD are at high risk as well. At present, there is no guideline for the treatment of cancer patients with COVID-19 infection. Our findings indicate that in addition to the treatment of COVID-19 itself, the treatment of tumors may be necessary for cancer patients. Most importantly, close attention should be paid to patients with UCEC in determining whether they are cured of COVID-19. And to this effect, we suggest the use of a nucleic acid test of curettage specimens from the endometrium in addition to the nasal swab test.