Dados do Trabalho

Título

Unveiling the immune response of oncologic patients against SARS-CoV-2 infection: An in-depth analysis of soluble and cellular factors leading to recovery or death.

Introdução

In 2019 an outbreak of unknown pneumonia was identified as the Coronavirus Disease 2019 (COVID-19). The illness, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has impacted many aspects of human life ever since. Despite the efforts to better understand the pathology, studies conducted on specific populations were lacking. In case of oncologic patients broad recommendations were made as a way to provide protection, but with little information about the immune response of individuals with different types of cancer.

Objetivo

In this study our main focus was to evaluate the systemic cellular and soluble immune responses of oncologic patients diagnosed with COVID-19. We also investigated the associations of different immune profiles to COVID-19 outcome.

Métodos

Our study was conducted through the analysis of soluble and cellular factors present in blood collected within the early days of COVID-19 diagnosis in two cohorts of oncologic patients: those with hematologic malignancies, and those with solid tumors. The main techniques implemented were multiple immune soluble analyte assays, to evaluate the concentrations of cytokines, chemokines, growth factors, and antibodies against SARS-CoV-2, and multiparametric flow cytometry, to evaluate the immune profile of different lymphocyte subpopulations. We also evaluated clinical data present on electronic health records to enhance the investigation and associations found. This study was approved by A.C.Camargo Cancer Center’s Research Ethics Committee under the number 2858/20.

Resultados

Our analysis shows that, among individuals with hematologic malignancies that progressed to death, there was an overall lack of T cell populations, as well as an exacerbated production of multiple inflammatory factors. Conversely, patients with higher frequencies of lymphocytes, activated B cells, and increased production of antibodies had only mild COVID-19. Among the solid tumors cohort we observed a less pronounced impact of soluble immune factors. Patients with a more regulated immune response had better outcomes, whereas individuals that progressed to death presented multiple exhausted T and B cell populations, and lacked a clear regulatory T cell population. Curiously, while exhaustion of T cells seems impactful for oncologic patients in general, the loss of specific lymphocyte subpopulations and possible cytokine-release syndrome observed among hematologic patients could be the most important factor leading to death, whereas the lack of immune regulation and broad exhaustion profile probably had a greater impact for patients with solid tumors.

Conclusões

Our work helps to shed light into the immune mechanisms associated with death and recovery among oncologic patients. Hematologic malignancies and solid tumors patients not only present different immune profiles against SARS-CoV-2 infection, but seem to progress through different courses of COVID-19, which highlights that the immune system has an important role in the outcome of the disease in this population.

Palavras-chave

COVID-19 and Cancer; Systemic Immune Profile; Disease Outcome

Financiador do resumo

CNPq, FAPESP, NIH, NIVEA