Original Article

Interferon-lambda 3 is involved in the permission of pneumonia development after infection with respiratory viruses including SARS-CoV-2

Lyudmila I. Nikolaeva1, Georgy V. Sapronov2, Veronika V. Dyachenko2, Nataliya M. Glagoleva2, Nadezhda G. Shevchenko2, Ekaterina G. Samokhvalova1, Evgenya A. Mukasheva1, Alexandra G. Rosatkevich1, Irina N. Khlopova1, Lylya N. Merkulova1, Irina S. Kruzhkova1, Alexander E. Grishechkin1, Svetlana V. Smetanina3, Lyudmila V. Kolobukhina1,2, Elena I. Burtseva1, Dmitry K. Lvov1

1Gamaleya National Research Center of Epidemiology and Microbiology, Ivanovsky Institute of Virology, Ministry of Health, Moscow, Russian Federation
2Central Clinical Hospital, Presidential Affairs of Russian Federation, Moscow, Russian Federation
3Infection Diseases Clinical Hospital Number 1, Moscow Department of Health, Moscow, Russian Federation


Background: The effectiveness of barrier function of the respiratory mucosa largely depends on interferons type I and type III. The IFNs forms the first level of innate immune protection. The single-nucleotide polymorphisms (SNPs) affecting IFN- 3 production were found previously. The study aimed to investigate a putative association of SNPs rs8099917 T/G located upstream IFNL3 gene and rs12979860 C/T within IFNL4 gene with a risk of pneumonia developing after infection with respiratory viruses.
Methods: The nasopharyngeal swabs, lavages, and blood samples from 318 patients infected with respiratory viruses were analyzed. Of these, 168 participants were shown to have community-acquired pneumonia, while the rest patients were diagnosed with bronchitis. The respiratory virus genomes were detected by real-time polymerase chain reaction (PCR) using commercially available kits. The DNA samples from all patients were used to detect SNPs rs8099917 T/G and rs12979860 C/T by real-time PCR using a commercially available kit. COVID-19 morbidity and mortality data were obtained from the WHO website.
Results: No association was found between different rs8099917 allelic variants and the development of pneumonia. The rs12979860 TT genotype was significantly more often detected in patients with pneumonia (p = 0.039; OR = 2.400; 95% CI 1.310 - 3.706). IFN-?3 production has been early found to be maximal with rs12979860 TT genotype. An association was established between rs12979860 T allele frequency and COVID-19 mortality rate in 13 countries.
Conclusions: The rs12979860 TT genotype is a genetic marker of increased risk of pneumonia after infection with respiratory viruses. High T allele frequency may be an indicator of a higher COVID-19 mortality rate. Patients with rs12979860 TT genotype have an increased risk of developing COVID-19 pneumonia.

Keywords: COVID-19; genetic polymorphisms; IFN-?; pneumonia; respiratory virus infection