{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:14:50Z","timestamp":1789697690412,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Microbiology"],"published-print":{"date-parts":[[2023,12,21]]},"abstract":"<jats:p>Introduction. The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results. The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT\u2009+\u2009TT, odds ratio (95% confidence interval): 12.136 (2.784\u201352.896) and IFITM-3 rs12252 AG\u2009+\u2009GG: 17.276 (3.673\u201381.249), both <jats:inline-formula><a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><a:mi>p<\/a:mi><a:mo>&lt;<\/a:mo><a:mn>0.001<\/a:mn><\/a:math><\/jats:inline-formula>. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (<jats:inline-formula><c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><c:mi>p<\/c:mi><c:mo>&lt;<\/c:mo><c:mn>0.001<\/c:mn><\/c:math><\/jats:inline-formula>). Conclusion. ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.<\/jats:p>","DOI":"10.1155\/2023\/6384208","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T23:20:07Z","timestamp":1703200807000},"page":"1-12","source":"Crossref","is-referenced-by-count":3,"title":["Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2046-537X","authenticated-orcid":true,"given":"Amal F.","family":"Makled","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3885-0388","authenticated-orcid":true,"given":"Sahar A. M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-2527","authenticated-orcid":true,"given":"S. S.","family":"Eldahdouh","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases and Tuberculosis, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6464-787X","authenticated-orcid":true,"given":"Asmaa S.","family":"Sleem","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3827-7683","authenticated-orcid":true,"given":"Maha M.","family":"Eldahshan","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2256-6806","authenticated-orcid":true,"given":"Yara","family":"Elsaadawy","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0207-8399","authenticated-orcid":true,"given":"Samar S.","family":"Salman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-4511","authenticated-orcid":true,"given":"Asmaa","family":"Mohammed Elbrolosy","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"4","key":"1","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.ygeno.2021.04.002","article-title":"Interferon-induced transmembrane protein-3 genetic variant RS12252 is associated with covid-19 mortality","volume":"113","author":"J. 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Morena","year":"2020","journal-title":"European Journal of Internal Medicine"},{"key":"53","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.imlet.2020.10.009","article-title":"Pulmonary vascular improvement in severe COVID-19 patients treated with tocilizumab","volume":"228","author":"L. Salvati","year":"2020","journal-title":"Immunology Letters"},{"issue":"2","key":"54","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.02523-2021","article-title":"CORIMUNO-19 Collaborative Group \u201cEffect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group. \u201cPulmonary vascular improvement in severe COVID-19 patients treated with tocilizumab","volume":"60","author":"O. Hermine","year":"2022","journal-title":"European Respiratory Journal"},{"issue":"6","key":"55","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1001\/jama.2021.11330","article-title":"Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis","volume":"326","author":"Who Rapid Evidence Appraisal for Covid-19 Therapies (React) Working Group","year":"2021","journal-title":"Journal of the American Medical Association"},{"key":"56","article-title":"Coronavirus disease (COVID-19), Post COVID-19 condition","author":"World Health Organization","year":"2023"},{"key":"57","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.cmi.2020.09.052","article-title":"Follow-up of adults with noncritical COVID-19 two months after symptom onset","volume":"27","author":"C. 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