Abstract
Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer leading to elevated mortality rates. 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 have so far been poorly investigated. We conducted a multi-omic analysis of immunological parameters in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with and without cancer. Healthy donors and SARS-CoV-2-negative cancer patients were also included as controls. At the infection peak, cytokine multiplex analysis of blood samples, cytometry by time of flight (CyTOF) cell population analyses, and Nanostring gene expression using Pancancer array on PBMCs were performed. We found that eight pro-inflammatory factors (IL-6, IL-8, IL-13, IL-1ra, MIP-1a, IP-10) out of 27 analyzed 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 (MAIT), natural killer (NK), and γδ T cells were reduced, while B plasmablasts were expanded in COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients. A 19-gene expression signature of PBMCs is able to discriminate COVID-19 patients with and without solid cancers. Gene set enrichment analysis highlights an increased gene expression linked to Interferon α, γ, α/β response and signaling which paired with aberrant cell cycle regulation in cancer patients. Ten out of the 19 genes, validated in a real-world consecutive cohort, were specific of COVID-19 cancer patients independently from different cancer types and stages of the diseases, and useful to stratify patients in a COVID-19 disease severity-manner. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients.
Highlights
The impact of the COVID-19 pandemic on cancer patients has become a major focus of the investigation
In five out of 19 patients with cancer (Fig. 2A). This reduction was mainly due to terminal effectors CD8+ T cells that are back to the levels observed in healthy donors (HD), and Mucosal-associated invariant T (MAIT)-NKT cells
An immune and proliferation transcriptional network is activated in COVID-19 cancer patients Taking advantage of the Genome Browser ChIP-seq databases at the University of California Santa Cruz (UCSC) (ENCODE tracks), we looked for a common binding signature of transcription factors to the promoters of the genes modulated in COVID-19 cancer patients
Summary
The impact of the COVID-19 pandemic on cancer patients has become a major focus of the investigation. The development of cancer itself, surgical treatment and related procedures, radiotherapy, and/or systemic treatments may lead to immune suppression [3], increasing the risk of SARS-Cov-2 infection [4,5,6]. Serum cytokines are aberrantly produced expressed at higher levels in the COVID-19 subjects than in HD in these patients and circulating subsets of immune cells are sera (Fig. 1b–d). Lymphocytes' could be observed in male COVID-19 subjects compared to the gene expression profiles are deeply modified in Covid-19 patients non-gender segregated group (Fig. 1e) while the same does not and these alterations are further enhanced with disease severity [11,12,13].
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