Association between polymorphisms in TLR3, TICAM1 and IFNA1 genes and covid-19 severity in Southern Brazil

ABSTRACT

Background

A distinct phenotype in Coronavirus disease 2019 (Covid-19) was observed in severe patients, consisting of a highly impaired interferon (IFN) type I response, an exacerbated inflammatory response.

Objective

The aim of the present study was to investigate a possible association of single nucleotide polymorphisms (SNPs), in five genes related to the immune response, rs3775291 in TLR3; rs2292151 in TICAM1; rs1758566 in IFNA1; rs1800629 in TNF, and rs1800795 in IL6 with the severity of Covid-19.

Methods

A cross-sectional study was performed, with non-severe and severe/critical patients diagnosed with Covid-19, by two public hospitals in Brazil. In total, 300 patients were genotyped for the SNPs, 150 with the non-severe form of the disease and 150 with severe/critical form.

Results

The T/T genotype of TLR3 in recessive model shows 58% of protection against severe/critical Covid-19; as well as the genotypes G/A+A/A of TICAM1 in dominant model with 60% of protection, and in a codominant model G/A with 57% and A/A with 71% of protection against severe/critical Covid-19. Comparing severe and critical cases, the T/C genotype of IFNA1 in the codominant model and TC+C/C in the dominant model showed twice the risk of critical Covid-19.

Conclusion

We can conclude that rs3775291, rs2292151 and rs1758566 can influence the COVID-19 severity.

KEYWORDS:

• Toll like receptor
• cytokines
• polymorphism
• coronavirus
• innate immune response

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2024.2367466

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M Braga executed the research protocol, analyzed the data, and wrote the manuscript. MAS Shiga, PES Silva and AHU Yamanaka executed the research protocol. VH Souza, S Grava, JSF Neves and ANC Simão contributed to the collection of data, sample and classification of patients. QAL Neto supervised the analyses and the execution of this research. JMV Zacarias and JEL Visentainer developed the original idea and provided intellectual input and critical analysis of the manuscript. All authors contributed to the article and approved the submitted version.

Acknowledgments

The authors wish to thank the patients and volunteers for their valuable participation in the study, the Postgraduate Program in Biosciences and Physiopathology - State University of Maringá (UEM), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Ethical approval

This research was approved by the Standing Committee of Ethics of the State University of Maringá (38095420.5.0000.0104) and Standing Committee of Ethics of the State University of Londrina (31656420.0.0000.5231), and all participants signed an informed consent form.

Additional information

Funding

This work was supported by the Laboratory of Immunogenetics [Proc. n.1589/2017-CSD-UEM].