Distribution of Interferon Lambda 4 Single Nucleotide Polymorphism rs11322783 Genotypes in Patients with COVID-19

Abstract

Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.

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

“…In addition, we have noticed considerably higher number of WBC with increment of neutrophils in patients who died in‐hospital and were predominantly TT carriers. Further analysis confirmed that all TT carriers had significantly higher WBC count with increased (albeit nonsignificant) neutrophils percentage, which is in line with the previous study reporting the preponderance of homozygous carriers of ΔG in patients with lower WBC and lower neutrophil count 13 . On the other hand, N/L ratio, as one of the most provable risk factors in COVID‐19, was not affected by rs368234815 variant.…”

“…Further analysis confirmed that all TT carriers had significantly higher WBC count with increased (albeit nonsignificant) neutrophils percentage, which is in line with the previous study reporting the preponderance of homozygous carriers of ΔG in patients with lower WBC and lower neutrophil count. 13 On the other hand, N/L ratio, as one of the most provable risk factors in COVID-19, was not affected by rs368234815 variant. There were opposite reports as well, rs368234815 TT/TT as a favorable genotype being found at higher frequency among COVID-19 survivors as compared to those who did not survive infection, 14 and carriers of ΔG/ΔG displaying lower ability in SARS-CoV-2 clearance, although not influencing the clinical outcome of the disease.…”

“…Given all the similarities between HCV and COVID‐19, it would be interesting to examine the potential role of IFNLs polymorphisms in SARS‐CoV‐2 infection. Indeed, some of the recent studies addressed the link of IFNL3 and IFNL4 polymorphisms with SARS‐CoV‐2 susceptibility, COVID‐19 severity and outcome of the disease 11‐13 . As far as the impact of IFNL3 and IFNL4 polymorphisms on COVID‐19 outcome pertains, patient who concomitantly carry rs368234815 TT/TT, rs12979860 C/C, rs8099917 T/T, and rs12980275 A/A genotypes were associated with lower risk of death 14 .…”

“…Indeed, some of the recent studies addressed the link of IFNL3 and IFNL4 polymorphisms with SARS-CoV-2 susceptibility, COVID-19 severity and outcome of the disease. [11][12][13] As far as the impact of IFNL3 and IFNL4 polymorphisms on COVID-19 outcome pertains, patient who concomitantly carry rs368234815 TT/TT, rs12979860 C/C, rs8099917 T/T, and rs12980275 A/A genotypes were associated with lower risk of death. 14 Another study observed rs12979860 T/C association with increased fatality ratio.…”

Association of Interferon Lambda 3 and 4 Gene SNPs and Their Expression with COVID-19 Disease Severity: A Cross-Sectional Study

“…8,9 Similarly, IFNL4 has been shown to have anti-viral activity against MERS-CoV and, therefore, may also play an important role in conferring protection against SARS-CoV-2 infections. [10][11][12] The response emanating from the interferons is affected by the host as well as viral factors. 13 These factors primarily include the viral load and the age of the patient.…”