Abstract
The cellular immune response plays an important role in COVID-19, caused by SARS-CoV-2. This feature makes use of in vitro models’ useful tools to evaluate vaccines and biopharmaceutical effects. Here, we developed a two-step model to evaluate the cellular immune response after SARS-CoV-2 infection-induced or spike protein stimulation in peripheral blood mononuclear cells (PBMC) from both unexposed and COVID-19 (primo-infected) individuals (Step1). Moreover, the supernatants of these cultures were used to evaluate its effects on lung cell lines (A549) (Step2). When PBMC from the unexposed were infected by SARS-CoV-2, cytotoxic natural killer and nonclassical monocytes expressing inflammatory cytokines genes were raised. The supernatant of these cells can induce apoptosis of A549 cells (mock vs. Step2 [mean]: 6.4% × 17.7%). Meanwhile, PBMCs from primo-infected presented their memory CD4+ T cells activated with a high production of IFNG and antiviral genes. Supernatant from past COVID-19 subjects contributed to reduce apoptosis (mock vs. Step2 [ratio]: 7.2 × 1.4) and to elevate the antiviral activity (iNOS) of A549 cells (mock vs. Step2 [mean]: 31.5% × 55.7%). Our findings showed features of immune primary cells and lung cell lines response after SARS-CoV-2 or spike protein stimulation that can be used as an in vitro model to study the immunity effects after SARS-CoV-2 antigen exposure.
Highlights
The infection caused by the new coronavirus (SARS-CoV-2) induces a severe acute respiratory syndrome, with signals and symptoms such as fever, cough, and pneumonia, namely COVID-19 [1,2]
The analysis of absolute frequency of phenotypes before stimulation showed that lymphocytes (T and B cells) were more frequent than monocytes and natural killer cells in the peripheral blood cells from all participants, showing no difference between unexposed and COVID-19 groups (Table 3)
Several studies have already demonstrated that the new coronavirus (SARS-CoV-2) is able to infect cells in the respiratory tract, but other organs, such as blood [30–33]
Summary
The infection caused by the new coronavirus (SARS-CoV-2) induces a severe acute respiratory syndrome, with signals and symptoms such as fever, cough, and pneumonia, namely COVID-19 [1,2]. This virus of high transmissibility and high mortality rates among respiratory infections has collapsed the intensive care units of hospitals around the world [1,2]. As the SARS-CoV-2 variants were emerging in some parts of the globe, the pandemic showed its strength scaling up new cases and mortality rates, contributing to several countries joining in a race for mass immunization [3–7]. Immune response is a key part of the clinical evolution of the disease, in which cytokine storm, leucopenia, and lung infiltrating macrophages and neutrophils are associated with poorer outcomes [2,9,10]. Few studies are focused on Latin American countries, in which socio-economic issues are always challenging and genetic factors can influence different responses [13]
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