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Παρασκευή 20 Ιανουαρίου 2023

IFNL3/4 polymorphisms as a two‐edged sword: an association with COVID‐19 outcome

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ABSTRACT

Background

COVID-19 has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis.

Aim of the study

With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality.

Methods

This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 SNPs, namely rs12980275, rs8099917, rs12979860 and rs368234815.

Results

21.9% and 65.0% of ho spitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased CCI, N/L, and LDH level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19.

Conclusion

Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19.

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