4.7 Article

Elevation in viral entry genes and innate immunity compromise underlying increased infectivity and severity of COVID-19 in cancer patients

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SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-021-83366-y

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  1. Canadian Institutes of Health Research [PJT - 153289, 415148]
  2. Peter and Shelagh Godsoe Chair in Radiation Medicine
  3. Princess Margaret Cancer Centre
  4. Princess Margaret Cancer Foundation
  5. Ontario Ministry of Health
  6. Ministry of Science and Technology of Taiwan [MOST107-2320-B-038-034-MY3]
  7. Canada Research Chair in Translational Genomics
  8. Princess Margaret Foundation Gattuso-Slaight Personalized Cancer Medicine Fund
  9. Ontario Institute for Cancer Research

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Multiple studies have reported a doubling in the risk of COVID-19 among cancer patients, which may be attributed to the increased expression of critical viral entry genes in cancer states and the transient dysregulation of innate viral defenses during radiation treatments, especially in pediatric samples.
Multiple studies have reported a doubling in risk of Coronavirus Disease-2019 (COVID-19) among cancer patients. Here, we examine the potential biological rationale behind this recurrent epidemiological observation. By leveraging large-scale genome-wide transcriptional data of normal and malignant tissues from adults and children, we found evidence of increased expression of SARS-CoV-2 viral entry genes in the cancer state, particularly in respiratory, gastrointestinal, and genitourinary tract tissues, with decreased expression in pediatric vs. adult samples. Additionally, by interrogating the temporal effects of radiotherapy on human peripheral blood mononuclear and mucosal cells, we observed important treatment-related alterations in host innate immunity, specifically type I interferon responses. Overall, cancers enhance expression of critical viral entry genes, and innate viral defenses can be dysregulated transiently during radiation treatments. These factors may contribute to the observed increased susceptibility to SARS-CoV-2 entry and severity of COVID-19 in cancer patients.

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