Impairment of type I/III IFN response in the upper airways of sarscov-2 patients

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the most severe public healthcare concern. Interferon (IFN) represents a critical, first-line defense to viral infection and injury as part of innate immunity. Therefore, in order to provide additional insights to the pathogenesis of SARS-CoV-2, we delineated IFN signatures in the upper respiratory tract of 2019-nCoV patients through the investigation of genes encoding type I/III IFNs, IFN-regulatory factor 7 (IRF-7) and IFN stimulated genes (ISGs). Methods: Respiratory samples of 54 patients with symptomatic SARS-CoV-2 infection and 29 negative healthcare workers were collected in our study. Oropharyngeal swabs were divided into two aliquots one was treated for SARSCoV-2 detection and one was used to extract total RNA from pellet cells and to analyze gene expression of IFN-alfa, IFN-beta, IFN-lambda 1-3, IRF7, ISG15, and ISG56 through RT/Real Time PCR. Results: Overall IFN-alfa, IFN-beta, IFN-lambda 1-3, IRF7, and ISGs mRNA levels in oropharyngeal swabs were significantly increased in SARS-CoV-2 infected patients compared to those detected in healthcare workers. SARS-CoV-2 threshold cycle (Ct) values negatively correlated to ISG15, ISG56 and IRF7 mRNAs levels (ISG15 r=-0.3066, p=0.0405;ISG56 r=-0.3672, p=0.0182;IRF7 r=-0.3733, p=0.0192). Interestingly, the subgroup of 6 patients who were supported by invasive mechanical ventilation showed a general decrease in the expression of some IFN genes with a significant lower level of ISG15 and ISG56, compared to the patients who do not required oxygen support and those who received non-invasive ventilation (p<0.05;p<0.05). Conclusion: Our results suggest a differential IFN-I/III signature in the respiratory tract of SARS-CoV-2 patients, depending on development of immunopathology and severe disease. Understanding of the effects of SARSCoV-2 on the overall innate immune response with the final aim to shed new light on COVID-19 pathogenesis and design a tailored immune-therapy for SARS-CoV-2 infected patients.