Multi-omic approach identifies a transcriptional network coupling innate immune response to proliferation in the blood of COVID-19 cancer patients

Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer for which mortality rate in cancer patients affected by COVID-19 is elevated. SARS-CoV-2 infection is known to alter immune system homeostasis. Whether cancer patients developing COVID-19 present alterations of immune functions which might contribute to worse outcomes has been so far poorly investigated. We conducted a multi-omic analysis of immunological parameters in COVID-19 patients with and without cancer. We found that 8 pro-inflammatory factors out of 27 analysed serum cytokines were modulated in COVID-19 patients irrespective of cancer status. Diverse subpopulations of T lymphocytes such as CD8+ T, CD4+ T central memory, Mucosal associated invariant T cells (MAIT) NKT and  T cells were reduced while B memory cells, plasmablasts, late NK and plasmacytoid dendritic cells were expanded in COVID-19 cancer patients. A 19 gene expression signature of peripheral blood cells was able to discriminate COVID-19 cancer and without cancer patients. Gene set enrichment analysis highlights an increased gene expression in Interferon  response and signalling which paired with aberrant cell cycle regulation in cancer patients. Ten out of these 19 genes were specific of COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients that might contribute to decipher their higher frequency of severe events. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients. This might also lead to design of novel therapeutic strategies for COVID-19 cancer patients. 12 PBMC samples were analyzed. 5 are COVID-19 patients, 5 are COVID-19 patients with cancer and 2 are healthy subjects.