TYK2, IFITM3, IFNAR2 and OAS3 single-nucleotide polymorphisms among severe COVID-19 ICU patients in Morocco

R Benmansour; M R Tagajdid; H El Hamzaoui; S Fjouji; N Doghmi; A Houba; I Belbacha; S Elkochri; R Aabi; H Elannaz; A Laraqui; B El Mchichi; T Chmitah; N Touil; K Ennibi; R Eljaoudi; E Elmir; I Amine Lahlou; H Oumzil

doi:10.1177/03946320241257241

TYK2, IFITM3, IFNAR2 and OAS3 single-nucleotide polymorphisms among severe COVID-19 ICU patients in Morocco

Int J Immunopathol Pharmacol. 2024 Jan-Dec:38:3946320241257241. doi: 10.1177/03946320241257241.

Authors

R Benmansour¹, M R Tagajdid¹, H El Hamzaoui², S Fjouji³, N Doghmi³, A Houba³, I Belbacha⁴, S Elkochri¹, R Aabi¹, H Elannaz¹, A Laraqui¹, B El Mchichi¹, T Chmitah¹, N Touil¹, K Ennibi¹, R Eljaoudi⁵, E Elmir⁴, I Amine Lahlou¹, H Oumzil⁵

Affiliations

¹ Center of Virology, Infectious and Tropical Diseases, Mohamed V Military Teaching Hospital, University Mohammed V in Rabat, Rabat, Morocco.
² Emergency Department, University Hospital Ibn Sina, Rabat, And School of Medicine and Pharmacy, University Mohamed V in Rabat, Rabat, Morocco.
³ Department of Anesthesia, Mohamed V Military Teaching Hospital, University Mohammed V in Rabat, Rabat, Morocco.
⁴ Virology Department, Institut National D'Hygiène, Rabat, Morocco.
⁵ Medical Biotechnology Laboratory, School of Medicine and Pharmacy, University Mohammed V in Rabat, Rabat, Morocco.

Abstract

Objectives: This study aimed to explore the potential correlation between specific single nucleotide polymorphisms (TYK2, IFITM3, IFNAR2, and OAS3 variants) and the severity of COVID-19 in Moroccan patients.

Methods: A genetic analysis was conducted on 109 patients with PCR-confirmed SARS-CoV-2 infection in Morocco. Among these patients, 46% were hospitalized in the intensive care unit, while 59% were not hospitalized. Importantly, all patients lacked known risk factors associated with COVID-19 severity. Genotyping was performed to identify variations in TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079. Statistical analysis was applied using codominant, dominant and recessive logistic regression models to assess correlations with COVID-19 severity.

Results: Our findings revealed no significant correlation between TYK2 rs74956615, IFITM3 rs12252, IFNAR2 rs2236757, and OAS3 rs10735079 with COVID-19 severity in Moroccan patients, as indicated in logistic regression models (p > .05). Interestingly, these results may offer insights into the mitigated impact of the COVID-19 pandemic and the reduced severity observed in SARS-CoV-2 infected patients in Morocco. Age, however, exhibited a significant correlation with severity (p < .001), with a trend towards increased likelihood of ICU admission with advancing age. Additionally, In the severe group, a higher proportion of patients were females (54%), indicating a statistically significant correlation with disease severity (p = .04). Nevertheless, female ICU patients aged above 60 years accounted for 37%, compared to 17% for males.

Conclusion: This study underscores the absence of a genetic association between the selected polymorphisms and COVID-19 severity in Moroccan patients. Advanced age emerges as the primary factor influencing the severity of COVID-19 patients without comorbidities. We recommend setting the threshold for advanced age at 60 years as a risk factor for severe forms of COVID-19.

Keywords: COVID-19; IFITM3; IFNAR2; OAS3; TYK2; genetic polymorphism; host genetics; severity.

MeSH terms

2',5'-Oligoadenylate Synthetase / genetics
Adult
Aged
COVID-19* / epidemiology
COVID-19* / genetics
Female
Genetic Predisposition to Disease
Humans
Intensive Care Units*
Male
Membrane Proteins* / genetics
Middle Aged
Morocco / epidemiology
Polymorphism, Single Nucleotide*
RNA-Binding Proteins* / genetics
Receptor, Interferon alpha-beta* / genetics
SARS-CoV-2 / genetics
Severity of Illness Index*
TYK2 Kinase* / genetics

Substances

IFITM3 protein, human
IFNAR2 protein, human
TYK2 protein, human