Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations. OBJECTIVES: Determine associations of demograp...

Full description

Saved in:
Bibliographic Details
Main Authors: Shukur Wasman Smail, Esmaeil Babaei, Kawa Amin
Format: Article
Language:English
Published: King Faisal Specialist Hospital and Research Centre 2023-05-01
Series:Annals of Saudi Medicine
Online Access:http://www.annsaudimed.net/doi/10.5144/0256-4947.2023.125
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849423030045900800
author Shukur Wasman Smail
Esmaeil Babaei
Kawa Amin
author_facet Shukur Wasman Smail
Esmaeil Babaei
Kawa Amin
author_sort Shukur Wasman Smail
collection DOAJ
description BACKGROUND: Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations. OBJECTIVES: Determine associations of demographic, clinical, laboratory, and single nucleotide polymorphisms in the ACE2, TMPRSS2, TNF-α, and IFN-γ genes to the incidence of infection and mortality in COVID-19 patients. DESIGN: Prospective cohort study SETTINGS: Various cities in the Kurdistan Region of Iraq. PATIENTS AND METHODS: This prospective cohort study compared laboratory markers (D-dimer, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], C-reactive protein [CRP], lymphocyte and neutrophil counts) between COVID-19 patients and healthy controls. DNA was extracted from blood, and genotypes were done by Sanger sequencing. MAIN OUTCOME MEASURES: Single nucleotide polymorphisms of the ACE2, TMPRSS2, TNF-α, and IFN-γ genes and demographic characteristics and laboratory markers for predicting mortality in COVID-19. SAMPLE SIZE: 203 (153 COVID-19 patients, 50 health control subjects). RESULTS: Forty-eight (31.4%) of the COVID-19 patients died. Age over 40 and comorbidities were risk factors for mortality, but the strongest associations were with serum IFN-γ, the neutrophil-to-lymphocyte ratio (NLR), and serum TNF-α. The AA genotype and A allele of TMPRSS2 rs2070788 decreased while the GA genotype and A allele of TNF-α increased susceptibility to COVID-19. Patients with the GA genotype of TNF-α rs1800629 had shorter survival times (9.9 days) than those carrying the GG genotype (18.3 days) (P<.0001 by log-rank test). The GA genotype versus the GG genotype was associated with higher levels of serum TNF-α. The GA genotype increased mortality rates by up to 3.8 fold. The survival rate for COVID-19 patients carrying the IFN-γ rs2430561 TT genotype (58.5%) was lower than in patients with the TA and AA genotypes (80.3%). The TT genotype increased the risk of death (HR=3.664, P<.0001) and was linked to high serum IFN-γ production. Olfactory dysfunction was a predictor of survival among COVID-19 patients. CONCLUSIONS: Age older than 40, comorbidities, the NLR and particular genotypes for and the IFN-γ and TNF-α genes were risk factors for death. Larger studies in different populations must be conducted to validate the possible role of particular SNPs as genetic markers for disease severity and mortality in COVID-19 disease. LIMITATIONS: Small sample size. CONFLICT OF INTEREST: None.
format Article
id doaj-art-a6e78ed1dda447f18fcaab5bbcaa698c
institution Kabale University
issn 0256-4947
0975-4466
language English
publishDate 2023-05-01
publisher King Faisal Specialist Hospital and Research Centre
record_format Article
series Annals of Saudi Medicine
spelling doaj-art-a6e78ed1dda447f18fcaab5bbcaa698c2025-08-20T03:30:49ZengKing Faisal Specialist Hospital and Research CentreAnnals of Saudi Medicine0256-49470975-44662023-05-0143312514210.5144/0256-4947.2023.125Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish populationShukur Wasman Smail0Esmaeil Babaei1Kawa Amin2From the Department of Biology, College of Science, Salahaddin University-Erbil, IraqFrom the Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz, IranFrom the College of Medicine, University of Sulaimani, Sulaymaniyah, IraqBACKGROUND: Coronavirus disease 2019 (COVID-19) is a devastating pandemic that causes disease with a variability in susceptibility and mortality based on variants of various clinical and demographic factors, including particular genes among populations. OBJECTIVES: Determine associations of demographic, clinical, laboratory, and single nucleotide polymorphisms in the ACE2, TMPRSS2, TNF-α, and IFN-γ genes to the incidence of infection and mortality in COVID-19 patients. DESIGN: Prospective cohort study SETTINGS: Various cities in the Kurdistan Region of Iraq. PATIENTS AND METHODS: This prospective cohort study compared laboratory markers (D-dimer, tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], C-reactive protein [CRP], lymphocyte and neutrophil counts) between COVID-19 patients and healthy controls. DNA was extracted from blood, and genotypes were done by Sanger sequencing. MAIN OUTCOME MEASURES: Single nucleotide polymorphisms of the ACE2, TMPRSS2, TNF-α, and IFN-γ genes and demographic characteristics and laboratory markers for predicting mortality in COVID-19. SAMPLE SIZE: 203 (153 COVID-19 patients, 50 health control subjects). RESULTS: Forty-eight (31.4%) of the COVID-19 patients died. Age over 40 and comorbidities were risk factors for mortality, but the strongest associations were with serum IFN-γ, the neutrophil-to-lymphocyte ratio (NLR), and serum TNF-α. The AA genotype and A allele of TMPRSS2 rs2070788 decreased while the GA genotype and A allele of TNF-α increased susceptibility to COVID-19. Patients with the GA genotype of TNF-α rs1800629 had shorter survival times (9.9 days) than those carrying the GG genotype (18.3 days) (P<.0001 by log-rank test). The GA genotype versus the GG genotype was associated with higher levels of serum TNF-α. The GA genotype increased mortality rates by up to 3.8 fold. The survival rate for COVID-19 patients carrying the IFN-γ rs2430561 TT genotype (58.5%) was lower than in patients with the TA and AA genotypes (80.3%). The TT genotype increased the risk of death (HR=3.664, P<.0001) and was linked to high serum IFN-γ production. Olfactory dysfunction was a predictor of survival among COVID-19 patients. CONCLUSIONS: Age older than 40, comorbidities, the NLR and particular genotypes for and the IFN-γ and TNF-α genes were risk factors for death. Larger studies in different populations must be conducted to validate the possible role of particular SNPs as genetic markers for disease severity and mortality in COVID-19 disease. LIMITATIONS: Small sample size. CONFLICT OF INTEREST: None.http://www.annsaudimed.net/doi/10.5144/0256-4947.2023.125
spellingShingle Shukur Wasman Smail
Esmaeil Babaei
Kawa Amin
Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population
Annals of Saudi Medicine
title Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population
title_full Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population
title_fullStr Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population
title_full_unstemmed Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population
title_short Demographic, clinical and genetic factors associated with COVID-19 disease susceptibility and mortality in a Kurdish population
title_sort demographic clinical and genetic factors associated with covid 19 disease susceptibility and mortality in a kurdish population
url http://www.annsaudimed.net/doi/10.5144/0256-4947.2023.125
work_keys_str_mv AT shukurwasmansmail demographicclinicalandgeneticfactorsassociatedwithcovid19diseasesusceptibilityandmortalityinakurdishpopulation
AT esmaeilbabaei demographicclinicalandgeneticfactorsassociatedwithcovid19diseasesusceptibilityandmortalityinakurdishpopulation
AT kawaamin demographicclinicalandgeneticfactorsassociatedwithcovid19diseasesusceptibilityandmortalityinakurdishpopulation