The COVID-19 susceptibility of cancer patients might due to the high expression of SARS-CoV-2 required host factors.

Dear Editor,

Cancer patients have been disproportionately affected by the severe coronavirus disease 2019 (COVID-19) pandemic. Accumulating evidence suggests that patients with cancer are more likely to be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more likely develop a severe COVID-19. Some recent published researches in Journal of Infection have shown that the susceptibility of cancer patients to SARS-CoV-2 infection is closely associated with the expression of SARS-CoV-2 cell receptors , . However, the host receptor mediated initial attachment and entry of the virion to the host cell is only the first step of SARS-CoV-2 viral life cycle, the required host factors for the other key step of viral life cycle may also impact the susceptibility to SARS-CoV-2 infection of cancer patients.

Zharko Daniloski etc. have recently identified a series of required host factors for SARS-CoV-2 infection, which involve in regulating multiple steps of viral life cycle, including initial attachment (ACE2 and TMPRSS2) and endosomal entry (ACTR2, ACTR3, RAB7A, CCZ1B, ARPC3, ARPC4 and UVRAG), Spike cleavage and membrane fusion (ATP6AP1, ATP6AP2, ATP6V0B, ATP6V0C, ATP6V0D1, ATP6V1A, ATP6V1E1, ATP6V1G1, ATP6V1H, TMEM199 and CTSL), endosome recycling (VPS26A, VPS29, VPS35, SNX27, PIK3C3, WDR81, ACP5, COMMD2, COMMD3, COMMD3-BMI1 and COMMD4), viral RNA transcription (SLTM and SPEN), endoplasmic reticulum (DPM3 and ERMP1), and endoplasmic reticulum-Golgi trafficking (DPM3, ERMP1, PPID, and CHST14).

In this study, we investigated the expression patterns of all 37 SARS-CoV-2 required host factors in 31 available cancer types in the TCGA pan-cancer database from (Gene Expression Profiling Interactive Analysis) GEPIA to explain the potential reasons why cancer patients have higher risks of SARS-CoV-2 infection and severe outcomes. We found that the SARS-CoV-2 required host factors are significant up-regulated in the majority of cancer types (Fig. 1 ), especially in Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC), Pancreatic adenocarcinoma (PAAD), Thymoma (THYM), Cholangiocarcinoma (CHOL), suggesting the high expression of these factors may increase the risk of SARS-CoV-2 infection in cancer patients. In contrast, many of these factors expression were decreased in female genital cancers (Fig. 1), which is consistent with the prior report that patients with female genital cancers show relatively low risks of SARS-CoV-2 infection.

Fig. 1. Heatmap showing the difference in the 37 SARS-CoV-2 required host factors expression between the primary tumor and the normal tissues of 31 cancer types fromGEPIA. Red (> 1.0) indicated up-regulation of factor expression in tumor tissues; Blue (< 1.0) indicated down-regulation of factor expression in tumor tissues; *P < 0.05.

It has been shown that patients with late-stage cancer have higher risks of SARS-CoV-2 infection and a more severe COVID-19 trajectory. Thus, we analyzed the correlation between these factors expression and the tumor stage in human pan-cancer. Among all the 37 factors, the high expression levels of 24 factors were found to be correlated significantly with late pathological stage (Fig. 2 ), suggesting that the COVID-19 susceptibility of patients with late-stage cancer may due to the high expression of SARS-CoV-2 required host factors.

Fig. 2

Correlation between the expression levels of 24 SARS-CoV-2 required host factors and tumor stage in human pan-cancer (GEPIA).

In summary, the up-regulation of the required host factors for SARS-COV-2 infection in tumor tissues made cancer patients more likely to be infected by SARS-COV-2. We also suggested that most of these factors expression in tumor tissues increases with tumor stage, which may be one of the underlying mechanisms mediating the high risks of SARS-CoV-2 infection and severe outcomes observed in patients with late-stage cancer. We provided new insights into the biological linkage between SARS-CoV-2 and cancer. We hoped that our findings will help develop novel therapies for all patients with COVID-19.

Declaration of Competing Interest

The authors have no conflicts of interest to declare.