Implication of IL-12A, IL-12B, IL-6, and TNF single-nucleotide polymorphisms in severity and susceptibility to COVID-19.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has led to significant global morbidity and mortality. Understanding the genetic factors that influence disease outcomes can provide critical insights into pathogenesis and potential therapeutic targets. OBJECTIVE: This study aimed to investigate the potential correlation between single nucleotide polymorphisms (SNPs) in Interleukin 12 Subunit Alpha (IL-12A), Interleukin 12 Subunit Beta (IL-12B), Interleukin 6 (IL-6), and Tumor Necrosis Factor (TNF) genes and the severity as well as susceptibility to COVID-19 among Moroccan patients. PATIENTS AND METHODS: Next-Generation sequencing (NGS) was conducted on 325 Moroccan participants, 207 patients with PCR-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and 118 controls. Among these patients, 51% presented moderate to severe symptoms requiring hospitalization, while 49% were asymptomatic or experienced mild symptoms and did not require hospitalization. Statistical analysis was performed using codominant, dominant, and recessive logistic regression models to assess correlations with the severity and susceptibility to COVID-19 infection. RESULTS: No association was found between SNPs of IL-12A, IL-12B, IL-6 or TNF and COVID-19 severity and susceptibility. However, our results unveiled a noteworthy association with IL-6 rs2069840, which exhibited a negative correlation (OR = 0.21, 95% CI = 0.07-0.69, p = .006), suggesting a protective effect against SARS-CoV-2 infection. CONCLUSION: Polymorphisms in IL-12A, IL-12B, IL-6, and TNF genes are not correlated to the severity and susceptibility of COVID-19.

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

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.