Expressão de IFN, IL-17 e HERVs, e níveis séricos de IL-2, CCL2 e CCL3 associados à gravidade da COVID-19.

Abstract

COVID-19 is an acute respiratory disease caused by the coronavirus SARS-CoV-2. Its progression has been associated with hypoxia, unregulated systemic inflammation and coagulopathies, but the risk factors for its progression to the severe form are not yet fully understood. The poor prognosis of the disease appears to be associated with factors involved in the virus-host interaction, such as impaired signaling of type I IFN – the main line of innate defense for mounting an effective antiviral immune response – associated with a deregulated expression of pro-inflammatory cytokines. Furthermore, human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, appear to be reactivated in response to infectious agents such as SARS-CoV-2, modulating the innate immune response and leading to several systemic deleterious effects, but with a role in the worsening of the still incipient COVID-19. The present study analyzed gene expression and plasma levels of some molecules identified as markers of the severity of COVID-19, comparing mild and severe cases of the disease. 71 individuals (46 mild and 25 severe cases) were evaluated for gene expression analysis, and 139 for plasma cytokine measurement (58 mild and 81 severe cases). The expressions of the IFN genes and their receptors (INFAR1 and INFAR2), IL-17 and HERVs were analyzed in both groups, as well as the cytokines IL-2, CCL2 and CCL3. The expression of the INFAR2 gene (p<0.001) and the plasma concentration of the cytokine IL-2 (p<0.001) were higher in the mild group, while the plasma concentration of the chemokine CCL3 (p<0.001) was higher in the group with severe COVID. These findings enhance evidence on how the dynamics of the host's immune response can impact the clinical outcome of SARS-CoV-2 infection.