Distinct systemic immune networks define severe . mild COVID-19 in hematologic and solid cancer patients.
Flávio Pignataro-Oshiro, Amanda B Figueiredo, Nayane A L Galdino, Katia L P Morais, Walderez O Dutra, Bianca Grassi de Miranda Silva, Diego Feriani, Flávia de Azevedo Abrantes, Ivan Leonardo Avelino França E Silva, Jayr Schmidt Filho, Juliana Valéria de Souza Framil, Marcelle Goldner Cesca, Rachel Simões Pimenta Riechelmann, Marjorie V Batista, Kenneth J Gollob
Author Information
Flávio Pignataro-Oshiro: International Research Center, Translational Immuno-oncology Group, A.C.Camargo Cancer Center, São Paulo, Brazil.
Amanda B Figueiredo: International Research Center, Translational Immuno-oncology Group, A.C.Camargo Cancer Center, São Paulo, Brazil.
Nayane A L Galdino: International Research Center, Translational Immuno-oncology Group, A.C.Camargo Cancer Center, São Paulo, Brazil.
Katia L P Morais: International Research Center, Translational Immuno-oncology Group, A.C.Camargo Cancer Center, São Paulo, Brazil.
Walderez O Dutra: Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Bianca Grassi de Miranda Silva: Infectious Diseases Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Diego Feriani: Infectious Diseases Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Flávia de Azevedo Abrantes: Infectious Diseases Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Ivan Leonardo Avelino França E Silva: Infectious Diseases Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Jayr Schmidt Filho: Hematology Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Juliana Valéria de Souza Framil: Infectious Diseases Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Marcelle Goldner Cesca: Clinical Oncology Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Rachel Simões Pimenta Riechelmann: Clinical Oncology Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Marjorie V Batista: Infectious Diseases Department, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
Kenneth J Gollob: International Research Center, Translational Immuno-oncology Group, A.C.Camargo Cancer Center, São Paulo, Brazil.
Introduction: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted health across all sectors of society. A cytokine-release syndrome, combined with an inefficient response of innate immune cells to directly combat the virus, characterizes the severe form of COVID-19. While immune factors involved in the development of severe COVID-19 in the general population are becoming clearer, identification of the immune mechanisms behind severe disease in oncologic patients remains uncertain. Methods: Here we evaluated the systemic immune response through the analysis of soluble blood immune factors and anti-SARS-CoV-2 antibodies within the early days of a positive SARS-CoV-2 diagnostic in oncologic patients. Results: Individuals with hematologic malignancies that went on to die from COVID-19 displayed at diagnosis severe leukopenia, low antibody production against SARS-CoV-2 proteins, and elevated production of innate immune cell recruitment and activation factors. These patients also displayed correlation networks in which IL-2, IL-13, TNF-alpha, IFN-gamma, and FGF2 were the focal points. Hematologic cancer patients that showed highly networked and coordinated anti-SARS-CoV-2 antibody production, with central importance of IL-4, IL-5, IL-12A, IL-15, and IL-17A, presented only mild COVID-19. Conversely, solid tumor patients that had elevated levels of inflammatory cytokines IL-6, CXCL8, and lost the coordinate production of anti-virus antibodies developed severe COVID-19 and died. Patients that displayed positive correlation networks between anti-virus antibodies, and a regulatory axis involving IL-10 and inflammatory cytokines recovered from the disease. We also provided evidence that CXCL8 is a strong predictor of death for oncologic patients and could be an indicator of poor prognosis within days of the positive diagnostic of SARS-CoV-2 infection. Conclusion: Our findings defined distinct systemic immune profiles associated with COVID-19 clinical outcome of patients with cancer and COVID-19. These systemic immune networks shed light on potential immune mechanisms involved in disease outcome, as well as identify potential clinically useful biomarkers.
