Cytokine and Lymphocyte Profiles in COVID-19 Patients with Cancer: Implications for Disease Severity and Clinical...

Patients with cancer are at increased risk of severe outcomes from COVID-19. Yet, the immunological determinants underlying this vulnerability remain incompletely understood, particularly in low- and middle-income settings. Moreover, the impact of the severe viral disease surge and its compensatory mechanisms, such as stressed myelopoiesis, on this population needs further elucidation. This study aims to characterize the cytokine and lymphocyte profiles of cancer patients with COVID-19, correlate these profiles with disease severity, and compare them to those of non-cancer patients with COVID-19. Plasma cytokine, chemokine, and growth factor levels were quantified using Luminex technology, and immune cell subsets were characterized by flow cytometry. A total of 67 patients were analyzed: 40 with cancer (26 mild cases and 14 severe cases) and 27 without cancer (12 mild cases and 15 severe cases). Clinical outcomes showed an 86% mortality rate in cancer patients due to severe COVID-19. This contrasted with a 3.8% mortality rate in cancer patients with mild COVID-19, all unrelated to the infection. Our findings revealed elevated CXCL10 (IP-10) and reduced MIF levels in cancer patients with COVID-19, distinguished by disease severity. Compared with that in cancer patients with mild COVID-19, the level of CXCL10 in cancer patients with severe COVID-19 was further elevated. Additionally, cancer patients with COVID-19 presented reduced CD3⁺ T lymphocytes, expansion of CD4⁺CD25⁺FoxP3⁺ regulatory cells and CD56^BRIGHT NK cells, a shift from effector memory to central memory T-cells, and increased numbers of exhausted (PD-1⁺) T lymphocytes. In conclusion, our data suggest a distinct immunological profile observed in cancer patients with COVID-19. Especially in severe cases, viral surge-related suppressor cells and proinflammatory cytokines were accompanied by a compensatory immunosuppressive state, with decreased effector function and increased exhaustion. This may negatively impact clinical outcomes and highlight potential implications for the management of cancer patients.