Evaluation of the influence of immunomodulators on the innate immune response as a possible mechanism for reducing lung injury by COVID-19

The pandemic generated by the new coronavirus (SARS-CoV-2) has been a cause for concern, due to the occurrence of severe cases and high transmissibility. In Brazil, it is estimated that the number of beds in intensive care units will not be sufficient to attend to all cases that present severe pulmonary involvement. Therefore, the search for treatments that can reduce viral load or reduce the severity of lung injuries seen in most severe cases is extremely important and urgent. One of the drugs studied has been hydroxychloroquine (HCQ) which, despite the controversy regarding antiviral action, has known and studied immunomodulatory activity for years and has been applied frequently in the treatment of autoimmune and inflammatory diseases. In this context, the deepening of the study of HCQ immunomodulatory activities in order to verify its possible use in reducing cases that require ICU care for prolonged periods is considered relevant. HCQ works by inhibiting the activity of lysosomes, as well as cytokines such as TNF, IL-1, IL-6, INFα through the inhibition of Toll-Like receptors (TLR). In severe cases of COVID-19, there has been a disruption of the immune system, with an increase in neutrophils, increasing the neutrophil / lymphocyte ratio and triggering severe lung injury, similar to that triggered by LPS. It is known that, in neutrophils, HCQ reduces the concentration of intracellular calcium and reduces the production of oxidants. While chloroquine leads to a reduction in the production of extracellular neutrophil traps (NET), already known to be associated with lung injury. Thus, the present work intends to test the hypothesis that HCQ modulates the activity of neutrophils activated by LPS, reducing the respiratory burst, migration and phagocytic activity, preventing the delay in apoptosis and reducing the release of NET, using in vitro assays , by the functional, morphological and molecular evaluation of neutrophils exposed to HCQ and to LPS stimulation, compared to controls.