TY - JOUR
T1 - Elevation in viral entry genes and innate immunity compromise underlying increased infectivity and severity of COVID-19 in cancer patients
AU - Kwan, Jennifer Yin Yee
AU - Lin, Liang Tzung
AU - Bell, Rachel
AU - Bruce, Jeffrey P.
AU - Richardson, Christopher
AU - Pugh, Trevor J.
AU - Liu, Fei Fei
N1 - Funding Information:
The authors would like to acknowledge Ms. Lisa Chong for generation of the manuscript figure using BioRen-der. Funding for this work was provide by The Canadian Institutes of Health Research (#PJT – 153289, Vanier Canada Graduate Scholarship #415148), and The Peter and Shelagh Godsoe Chair in Radiation Medicine, Princess Margaret Cancer Centre, The Princess Margaret Cancer Foundation, and Ontario Ministry of Health. LTL is funded by the Ministry of Science and Technology of Taiwan (MOST107-2320-B-038-034-MY3). TJP holds the Canada Research Chair in Translational Genomics and is supported by the Princess Margaret Foundation Gattuso-Slaight Personalized Cancer Medicine Fund and a Senior Investigator Award from the Ontario Institute for Cancer Research.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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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U2 - 10.1038/s41598-021-83366-y
DO - 10.1038/s41598-021-83366-y
M3 - Article
C2 - 33633121
AN - SCOPUS:85101781236
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 4533
ER -
