Genetic variation of IFNL4 is associated with COVID-19

Abstract

COVID-19 currently represents a major public health problem. The causes that underlying susceptibility to infection in have not yet been determined. Interferons (IFNs) are intensively being investigated because of their antiviral properties. Among them, Interferon lambda 4 (IFNL4) has been reported to have antiviral activity against viral infections of the upper respiratory tract, Hepatitis virus C (HCV), and coronaviruses. The importance of this cytokine was shown by the fact that genetic variants of IFNL4 have been associated with viral clearance and response to IFNs-based therapies in HCV and other infections by RNA virus. In this study, we have investigated whether the rs12979860 polymorphism within the IFNL4 was also associated with COVID-19. Our findings show that the presence of the CC allele of rs12979860 was significantly lower in SARS-CoV-2 infected patients with regard to non-COVID-19 controls (38% vs 55%, p<0001). These results were not affected by sex, age, and severity of disease. These findings suggest that the CC allele may also confer protection against COVID-19. They may contribute to understanding the mechanisms of disease, the response to IFN-based treatments, and the racial differences observed in the disease.