The high expression of SARS-CoV-2 cell receptors might lead to higher COVID-19 infection rates in cancer patients.

Dear Editor,

We read with interest the recently published research in Journal of Infection by Dr. Cai et al., who observed the expression levels of SARS-CoV-2 receptor ACE2 and host cell protease TMPRSS2 in pan-cancer. Dr. Cai et al. suggested that the high expression of ACE2 and TMPRSS2 in cancer patients would increase the risk of the receptor binding to SARS-CoV-2, and Uterine corpus endometrial carcinoma (UCEC) patients might be the most susceptible to COVID-19. However, the distribution of ACE2 expression in human organs and tissues is not completely related to the organ tropism of SARS-COV-2, especially in the whole respiratory tract and a variety of immune cells, the expression of ACE2 is negative.2, 3, 4 Recent evidence highlights the possible presence of receptors other than ACE2 that mediates virus entry into host cells in different tissues, including membrane proteins LDLRAD3, TMEM30A, CLEC4G and AXL, and lysosomal protein TMEM106B , . In addition, ACE2-dependent co-receptor NRP1 was also ignored by Dr. Cai et al. , These might be potential reasons why Dr. Cai et al. 's results were inconsistent with previous observational studies.

In this study, we investigated the impact of all known potential SARS-COV-2 receptors in the four clinically observed tumor types most susceptible to COVID-19, including lung cancer, esophageal carcinoma, B-cell lymphoma and leukemia. NRP1, the ACE2-dependent co-receptor, and TMEM106B, a proviral host factor for SARS-CoV-2 were differentially expressed in all the four tumors. , Among the three potential SARS-COV-2 receptors identified by Zhu et al, LDLRAD3 was significantly up-regulated in lung cancer, esophageal carcinoma and B-cell lymphoma, CLEC4G was significantly up-regulated in leukemia, and TMEM30A was significantly up-regulated in esophageal carcinoma, B-cell lymphoma and leukemia. Interestingly, whether in normal tissues or tumor tissues, the level of ACE2 expression was quite low. We believed that the SARS-COV-2 receptor that made cancer patients more susceptible to infection was unlikely to be ACE2.

In summary, we explained the potential reasons why patients with four malignant tumors were more susceptible to COVID-19, namely the upregulation of SARS-COV-2 receptors in tumor tissues made individuals more likely to be infected by SARS-COV-2. We suggested NRP1, TMEM106B, LDLRAD3, TMEM30A and CLEC4G as a potential genetic shared genes for tumors and COVID-19, but ACE2 might not be included (Fig. 1).

Fig. 1

The expression levels of all known SARS-COV-2 receptors in four types of tumor patients that might more likely be infected by COVID-19. * P  < 0.05; ** P< 0.01; *** P< 0.001. (A) Lung cancer; (B) B-cell lymphoma; (C) Leukemia; (D) Esophageal carcinoma.