IFNL3/4 polymorphisms as a two-edged sword: An association with COVID-19 outcome

Area of Science:

• Genetics and Immunology
• Infectious Diseases
• Epidemiology

Background:

• Coronavirus Disease 2019 (COVID-19) is a major global health threat, with host immune responses influencing patient outcomes.
• Predicting COVID-19 mortality is crucial for effective patient management and resource allocation.

Purpose of the Study:

• To investigate the association between Interferon Lambda (IFNL) gene polymorphisms (IFNL3 and IFNL4) and other clinical factors with COVID-19 mortality.
• To identify genetic and clinical predictors for a more accurate prognosis of SARS-CoV-2 infection outcomes.

Main Methods:

• Prospective observational case-control study of 178 hospitalized COVID-19 patients.
• Data collection included demographic, clinical information, and genotyping for IFNL3/IFNL4 single nucleotide polymorphisms (SNPs) using TaqMan assays.
• Statistical analysis involved multivariable logistic regression to identify predictors of in-hospital death.

Main Results:

• In-hospital mortality was 21.9% for all hospitalized and 65.0% for critically ill patients.
• Increased Charlson Comorbidity Index (CCI), Neutrophil-to-Lymphocyte (N/L) ratio, and lactate dehydrogenase (LDH) levels were associated with higher mortality risk.
• Female patients and carriers of the IFNL3 rs8099917 variant allele had a significantly higher risk of death, while carriers of the IFNL4 rs368234815 ancestral allele had a significantly lower risk.

Conclusions:

• IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, along with patient gender, are significant predictors of COVID-19 outcome.
• Clinical markers such as LDH, N/L ratio, and CCI also play a crucial role in determining mortality risk.
• These findings can aid in timely prediction and management of severe COVID-19 cases.