Type I and III interferons are good markers to monitor COVID-19 pathophysiology

Abstract

The COVID-19 pandemic has caused millions of deaths and has resulted in disastrous societal and economic impacts worldwide. During SARS-CoV-2 infection, abnormal levels of pro-inflammatory cytokines have been observed and were associated to the severity of the disease. Type I (-α/β) and Type III (IFN-λ) interferons are family members of cytokines that play an important role in fighting viral replication during the early phases of infection. The location and timing of the IFNs production have been shown to be decisive for the COVID-19 outcome. Despite the effectiveness of COVID-19 vaccines and with the emergence of new SARS-CoV-2 variants, a better understanding of the involvement of IFNs as players in antiviral immunity in the COVID-19 pathophysiology is necessary to implement additional potent prophylactic and/or therapeutic approaches. In this study, we investigated the role of type I and III IFN in COVID-19 pathophysiology. We first analyzed the IFN-α, IFN-β and IFN- λ mRNA expression in nasopharyngeal swabs and blood samples from Moroccan patients infected with SARS-CoV-2 and secondly correlated these IFNs expressions with COVID-19 clinical and biological parameters. Our results showed that in the upper airways of patients with mild, non-severe, or severe COVID-19 manifestations, the IFN- α, - β and - λ are expressed in the same manner as in controls. However, in blood samples their expression was downregulated in all groups. Univariate linear models with interferons as predictors to evaluate clinical-biological parameters highlighted that the main clinical-biological relations were found when testing: FiO2, Lymphocyte values and virus load. Furthermore, the multivariate models confirmed that quantifications of interferons during COVID-19 are good biological markers for tracking COVID-19 pathophysiology.

Keywords: COVID-19; Immunity; Pathophysiology; Type I interferon; Type III interferon.