{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:26:12Z","timestamp":1789475172567,"version":"build-2803163510"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017160","name":"Beni Suef University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017160","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>By the end of December 2019, a new coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, and the cause of the disease was named coronavirus disease 2019 (COVID-19). Several genetic factors have been implicated in diverse responses to SARS-CoV-2 infection, such as the C-X-C chemokine receptor 4 (<jats:italic>CXCR4<\/jats:italic>) rs2228014 polymorphism, which has been previously studied in various diseases but has not been explored in the context of COVID-19 severity. The current study aimed to assess the association between the rs2228014 polymorphism in the <jats:italic>CXCR4<\/jats:italic> gene and the severity of COVID-19, which has not been previously reported.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>This cross-sectional study analyzed 300 adult Egyptian COVID-19 patients (156 with mild or moderate and 144 with severe or critical symptoms) admitted to Assiut University Quarantine Hospital from June to September 2022 during the omicron variant. The rs2228014 polymorphism in the <jats:italic>CXCR4<\/jats:italic> gene was detected using real-time PCR with a TaqMan assay probe. Receiver operating characteristic (ROC) curve analysis was used to determine the best cutoff values for C-reactive protein (CRP) that can be used to estimate the severity of COVID-19. P values less than 0.05 were considered to indicate statistical significance.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>No significant differences in the allelic or genotypic frequencies of <jats:italic>CXCR4<\/jats:italic> rs2228014 were detected between the severity groups. However, the exclusive presence of the AA genotype in mild or moderate cases suggests its potential protective role. Additionally, significant differences in myalgia presentation, leukocyte counts and antibiotic use, were observed among different genotypes. Statistical data showed that the severity of COVID-19 could be predicted at a cutoff value of CRP\u2009&gt;\u200930\u00a0mg\/L, with a sensitivity of 74.3% and a specificity of 42.9%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The present findings suggest a potential protective role of the AA genotype and A allele of <jats:italic>CXCR4<\/jats:italic> rs2228014 against severe COVID-19. Additionally, factors such as lack of vaccination and comorbidities such as hypertension, renal disease, and diabetes mellitus were associated with increased disease severity.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12879-024-09602-8","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T08:02:49Z","timestamp":1728979369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Potential protective association of the AA genotype and a allele of CXCR4 rs2228014 polymorphism with COVID-19 severity in adult egyptians"],"prefix":"10.1186","volume":"24","author":[{"given":"Osama H.","family":"Korayem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr E.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H.","family":"Meabed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa M.","family":"Magdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa M.","family":"Abdelghany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"9602_CR1","doi-asserted-by":"crossref","unstructured":"Shah VK, Firmal P, Alam A, Ganguly D, Chattopadhyay S. Overview of immune response during SARS-CoV-2 infection: lessons from the past, Front. Immunol, vol. 11, p. 1949, 2020.","DOI":"10.3389\/fimmu.2020.01949"},{"issue":"10224","key":"9602_CR2","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","volume":"395","author":"R Lu","year":"2020","unstructured":"Lu R, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565\u201374.","journal-title":"Lancet"},{"key":"9602_CR3","unstructured":"Organization WH. COVID-19 weekly epidemiological update, edition 127, 25 January 2023, 2023."},{"key":"9602_CR4","doi-asserted-by":"publisher","first-page":"112816","DOI":"10.1016\/j.envres.2022.112816","volume":"209","author":"R Khandia","year":"2022","unstructured":"Khandia R, et al. Emergence of SARS-CoV-2 Omicron (B. 1.1. 529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environ Res. 2022;209:112816.","journal-title":"Environ Res"},{"key":"9602_CR5","doi-asserted-by":"crossref","unstructured":"Sharma S, Aroura S, Gupta A, Priyadarshini A. Bioinformatics in diagnosis of COVID-19. Assess COVID-19 Other Pandemics Epidemics Using Comput Model Data Anal, pp. 197\u2013219, 2022.","DOI":"10.1007\/978-3-030-79753-9_12"},{"key":"9602_CR6","doi-asserted-by":"crossref","unstructured":"Asghar F, Hussain N, Komal F, Fatima Q. Sero-prevalence of Dengue IgM antibodies in patients suspected of having Dengue Fever. Annu Res Rev Biol, pp. 1\u201310, 2016.","DOI":"10.9734\/ARRB\/2016\/30090"},{"key":"9602_CR7","doi-asserted-by":"publisher","first-page":"112752","DOI":"10.1016\/j.bios.2020.112752","volume":"172","author":"M Y\u00fcce","year":"2021","unstructured":"Y\u00fcce M, Filiztekin E, \u00d6zkaya KG. COVID-19 diagnosis\u2014A review of current methods. Biosens Bioelectron. 2021;172:112752.","journal-title":"Biosens Bioelectron"},{"issue":"5","key":"9602_CR8","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","volume":"20","author":"MM Lamers","year":"2022","unstructured":"Lamers MM, Haagmans BL. SARS-CoV-2 pathogenesis. Nat Rev Microbiol. 2022;20(5):270\u201384.","journal-title":"Nat Rev Microbiol"},{"issue":"16","key":"9602_CR9","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1056\/NEJMoa2020283","volume":"383","author":"D Ellinghaus","year":"2020","unstructured":"Ellinghaus D, et al. Severe Covid-19 GWAS Group. Genomewide association study of severe Covid-19 with respiratory failure. N Engl j Med. 2020;383(16):1522\u201334.","journal-title":"N Engl j Med"},{"issue":"8","key":"9602_CR10","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41431-022-01136-4","volume":"30","author":"C Redin","year":"2022","unstructured":"Redin C, Thorball CW, Fellay J. Host genomics of SARS-CoV-2 infection. Eur J Hum Genet. 2022;30(8):908\u201314.","journal-title":"Eur J Hum Genet"},{"key":"9602_CR11","doi-asserted-by":"publisher","first-page":"703936","DOI":"10.3389\/fimmu.2021.703936","volume":"12","author":"O Tamgue","year":"2021","unstructured":"Tamgue O, et al. Non-coding RNAs in the etiology and control of major and neglected human tropical diseases. Front Immunol. 2021;12:703936.","journal-title":"Front Immunol"},{"key":"9602_CR12","doi-asserted-by":"crossref","unstructured":"Jia S-N, Han Y-B, Yang R, Yang Z-C. Chemokines in colon cancer progression. in Seminars in Cancer Biology. Elsevier; 2022.","DOI":"10.1016\/j.semcancer.2022.02.007"},{"key":"9602_CR13","doi-asserted-by":"crossref","unstructured":"Elemam NM, Hannawi S, Maghazachi AA. Role of chemokines and chemokine receptors in rheumatoid arthritis. ImmunoTargets Ther, pp. 43\u201356, 2020.","DOI":"10.2147\/ITT.S243636"},{"issue":"4","key":"9602_CR14","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/j.1365-2141.2007.06590.x","volume":"137","author":"JA Burger","year":"2007","unstructured":"Burger JA, B\u00fcrkle A. The CXCR4 chemokine receptor in acute and chronic leukaemia: a marrow homing receptor and potential therapeutic target. Br J Haematol. 2007;137(4):288\u201396.","journal-title":"Br J Haematol"},{"issue":"23","key":"9602_CR15","first-page":"4843","volume":"114","author":"D Crowther-Swanepoel","year":"2009","unstructured":"Crowther-Swanepoel D, et al. Genetic variation in CXCR4 and risk of chronic lymphocytic leukemia. Blood J Am Soc Hematol. 2009;114(23):4843\u20136.","journal-title":"Blood J Am Soc Hematol"},{"issue":"3","key":"9602_CR16","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/s41593-020-0585-y","volume":"23","author":"Y Werner","year":"2020","unstructured":"Werner Y, et al. Cxcr4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke. Nat Neurosci. 2020;23(3):351\u201362.","journal-title":"Nat Neurosci"},{"issue":"6","key":"9602_CR17","doi-asserted-by":"publisher","first-page":"e0130192","DOI":"10.1371\/journal.pone.0130192","volume":"10","author":"A Krieg","year":"2015","unstructured":"Krieg A, Riemer JC, Telan LA, Gabbert HE, Knoefel WT. CXCR4-A prognostic and clinicopathological biomarker for pancreatic ductal adenocarcinoma: a Meta-analysis. PLoS ONE. 2015;10(6):e0130192.","journal-title":"PLoS ONE"},{"key":"9602_CR18","unstructured":"Organization WH. WHO COVID-19: case definitions: updated in public health surveillance for COVID-19, published 16 December 2020. World Health Organization; 2020."},{"key":"9602_CR19","unstructured":"Masoud H, Elassal G, Hassany M, Shawky A, Abdel Hakim M, Zaky S. Management protocol for COVID-19 patients MoHP protocol for COVID19 November 2020. Cairo Egypt Minist Heal Popul Sch, 2020."},{"issue":"6","key":"9602_CR20","first-page":"873","volume":"139","author":"NH Ramzi","year":"2014","unstructured":"Ramzi NH, et al. Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia. Indian J Med Res. 2014;139(6):873\u201382.","journal-title":"Indian J Med Res"},{"key":"9602_CR21","unstructured":"Kirkpatrick LA. A simple guide to IBM SPSS statistics-Version 23.0. Cengage Learning; 2015."},{"key":"9602_CR22","doi-asserted-by":"publisher","first-page":"516957","DOI":"10.3389\/fgene.2020.00210","volume":"11","author":"N Abramovs","year":"2020","unstructured":"Abramovs N, Brass A, Tassabehji M. Hardy-Weinberg equilibrium in the large scale genomic sequencing era. Front Genet. 2020;11:516957.","journal-title":"Front Genet"},{"issue":"3","key":"9602_CR23","doi-asserted-by":"publisher","first-page":"e2107","DOI":"10.1002\/rmv.2107","volume":"30","author":"M Rokni","year":"2020","unstructured":"Rokni M, Ghasemi V, Tavakoli Z. Immune responses and pathogenesis of SARS-CoV\u20102 during an outbreak in Iran: comparison with SARS and MERS. Rev Med Virol. 2020;30(3):e2107.","journal-title":"Rev Med Virol"},{"issue":"4","key":"9602_CR24","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1002\/jmv.27477","volume":"94","author":"M Heidari Nia","year":"2022","unstructured":"Heidari Nia M, et al. Association of polymorphisms in tumor necrosis factors with SARS-CoV\u20102 infection and mortality rate: a case\u2010control study and in silico analyses. J Med Virol. 2022;94(4):1502\u201312.","journal-title":"J Med Virol"},{"issue":"1","key":"9602_CR25","doi-asserted-by":"publisher","first-page":"2027160","DOI":"10.1080\/21645515.2022.2027160","volume":"18","author":"I Mohammed","year":"2022","unstructured":"Mohammed I, et al. The efficacy and effectiveness of the COVID-19 vaccines in reducing infection, severity, hospitalization, and mortality: a systematic review. Hum Vaccin Immunother. 2022;18(1):2027160.","journal-title":"Hum Vaccin Immunother"},{"issue":"20","key":"9602_CR26","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1001\/jama.2021.19499","volume":"326","author":"MW Tenforde","year":"2021","unstructured":"Tenforde MW, et al. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA. 2021;326(20):2043\u201354.","journal-title":"JAMA"},{"key":"9602_CR27","doi-asserted-by":"publisher","unstructured":"Taoufiq R, Essabbani M, Mouhib NE, Mokahli S, Bougar S, Oubejja NE. Risk factors for Sever forms of COVID-19 - a second level Moroccan hospital experience. Adv Thorac Dis. 2021;2021. https:\/\/doi.org\/10.15342\/atd.2021.496.","DOI":"10.15342\/atd.2021.496"},{"key":"9602_CR28","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1007\/s10875-007-9164-1","volume":"28","author":"KI Alexandraki","year":"2008","unstructured":"Alexandraki KI, et al. Cytokine secretion in long-standing diabetes mellitus type 1 and 2: associations with low-grade systemic inflammation. J Clin Immunol. 2008;28:314\u201321.","journal-title":"J Clin Immunol"},{"key":"9602_CR29","doi-asserted-by":"publisher","first-page":"629933","DOI":"10.3389\/fcvm.2020.629933","volume":"7","author":"J Roberts","year":"2021","unstructured":"Roberts J, et al. Why is COVID-19 more severe in patients with diabetes? The role of angiotensin-converting enzyme 2, endothelial dysfunction and the immunoinflammatory system. Front Cardiovasc Med. 2021;7:629933.","journal-title":"Front Cardiovasc Med"},{"issue":"5","key":"9602_CR30","doi-asserted-by":"publisher","first-page":"e648","DOI":"10.1097\/FJC.0000000000001116","volume":"78","author":"M Peng","year":"2021","unstructured":"Peng M, He J, Xue Y, Yang X, Liu S, Gong Z. Role of hypertension on the severity of COVID-19: a review. J Cardiovasc Pharmacol. 2021;78(5):e648.","journal-title":"J Cardiovasc Pharmacol"},{"issue":"18","key":"9602_CR31","doi-asserted-by":"publisher","first-page":"3426","DOI":"10.1016\/j.cell.2022.08.004","volume":"185","author":"M Byrska-Bishop","year":"2022","unstructured":"Byrska-Bishop M, et al. High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios. Cell. 2022;185(18):3426\u201340.","journal-title":"Cell"},{"issue":"1","key":"9602_CR32","doi-asserted-by":"publisher","first-page":"92","DOI":"10.24869\/psyd.2020.92","volume":"32","author":"B Dalan","year":"2020","unstructured":"Dalan B, et al. Potential protective role of SDF-1 and CXCR4 gene variants in the development of Dementia. Psychiatr Danub. 2020;32(1):92\u20136.","journal-title":"Psychiatr Danub"},{"key":"9602_CR33","doi-asserted-by":"crossref","unstructured":"Okuyama NCM et al. CXCL12\/CXCR4 axis gene variants contribute to an increased vulnerability to HPV infection and cervical oncogenesis. J Cancer Res Clin Oncol, pp. 1\u201310, 2022.","DOI":"10.1007\/s00432-021-03884-0"},{"key":"9602_CR34","doi-asserted-by":"crossref","unstructured":"Matsusaka S, et al. Polymorphism of the chemokine CXCR4 to predict treatment benefit of first-line bevacizumab-based chemotherapy in patients with metastatic colorectal cancer. American Society of Clinical Oncology; 2015.","DOI":"10.1200\/jco.2015.33.3_suppl.635"},{"key":"9602_CR35","doi-asserted-by":"publisher","first-page":"652470","DOI":"10.3389\/fimmu.2021.652470","volume":"12","author":"N Reusch","year":"2021","unstructured":"Reusch N, et al. Neutrophils in COVID-19. Front Immunol. 2021;12:652470.","journal-title":"Front Immunol"},{"issue":"1","key":"9602_CR36","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/07853890.2020.1858234","volume":"53","author":"K Taniguchi-Ponciano","year":"2021","unstructured":"Taniguchi-Ponciano K, et al. Increased expression of hypoxia-induced factor 1\u03b1 mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients. Ann Med. 2021;53(1):197\u2013207.","journal-title":"Ann Med"},{"key":"9602_CR37","unstructured":"Zimmermann J, Klimkait T, Briand F, Obrecht D. Dual anti-viral and immunomodulatory activity of the CXCR4 inhibitor Balixafortide (POL6326) in preclinical in vitro and in vivo SARS-CoV2 infection models, Swiss Med. Wkly, pp. 14S-14S, 2021."},{"key":"9602_CR38","unstructured":"Muruh ZK, Al-alwani HR, Alhayani NN. Study the Association of Inflammatory Markers as CRP, LDH, D. Dimer and Ferritin with Severity of Covid19 Disease. Ann Rom Soc Cell Biol, pp. 2521\u201334, 2021."},{"issue":"8","key":"9602_CR39","doi-asserted-by":"publisher","first-page":"3507","DOI":"10.1007\/s12010-022-03885-w","volume":"194","author":"M Rokni","year":"2022","unstructured":"Rokni M, et al. Association of TMPRSS2 gene polymorphisms with COVID-19 severity and mortality: a case-control study with computational analyses. Appl Biochem Biotechnol. 2022;194(8):3507\u201326.","journal-title":"Appl Biochem Biotechnol"},{"key":"9602_CR40","doi-asserted-by":"crossref","unstructured":"Wang G, et al. C-reactive protein level may predict the risk of COVID-19 aggravation. in Open forum infectious diseases. Oxford University Press US; 2020. p. ofaa153.","DOI":"10.1093\/ofid\/ofaa153"},{"issue":"4","key":"9602_CR41","doi-asserted-by":"publisher","first-page":"500","DOI":"10.5937\/jomb0-27554","volume":"39","author":"M Ahnach","year":"2020","unstructured":"Ahnach M, Zbiri S, Nejjari S, Ousti F, Elkettani C. C-reactive protein as an early predictor of COVID-19 severity. J Med Biochem. 2020;39(4):500.","journal-title":"J Med Biochem"},{"issue":"11","key":"9602_CR42","doi-asserted-by":"publisher","first-page":"2409","DOI":"10.1002\/jmv.26097","volume":"92","author":"N Ali","year":"2020","unstructured":"Ali N. Elevated level of C-reactive protein may be an early marker to predict risk for severity of COVID\u201019. J Med Virol. 2020;92(11):2409.","journal-title":"J Med Virol"},{"key":"9602_CR43","doi-asserted-by":"crossref","unstructured":"Rokni M, IL1RN. Single nucleotide polymorphisms located in TNFA, IL6R, and IL6 genes are associated with COVID-19 risk and severity in an Iranian population, Cell Biol. Int, vol. 46, no. 7, pp. 1109\u20131127, 2022.","DOI":"10.1002\/cbin.11807"},{"issue":"7","key":"9602_CR44","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nrd1134","volume":"2","author":"E De Clercq","year":"2003","unstructured":"De Clercq E. The bicyclam AMD3100 story. Nat Rev Drug Discov. 2003;2(7):581\u20137.","journal-title":"Nat Rev Drug Discov"},{"key":"9602_CR45","doi-asserted-by":"crossref","unstructured":"Bekaddour N et al. Targeting the chemokine receptor CXCR4 with histamine analogue to reduce inflammation in juvenile arthritis: a proof of concept for COVID-19 therapeutic approach. bioRxiv, pp. 2010\u201321, 2021.","DOI":"10.1101\/2021.10.24.465080"},{"issue":"10229","key":"9602_CR46","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","volume":"395","author":"F Zhou","year":"2020","unstructured":"Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054\u201362.","journal-title":"Lancet"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09602-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-024-09602-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09602-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T19:02:49Z","timestamp":1729018969000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-024-09602-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,15]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["9602"],"URL":"https:\/\/doi.org\/10.1186\/s12879-024-09602-8","relation":{},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,15]]},"assertion":[{"value":"7 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participants were enrolled after they cheerfully and voluntarily agreed to participate in the present study. The protocol was approved by the Institutional Review Board of the Faculty of Medicine, Assiut University, Assiut, Egypt (local approval number: 17200716, date of approval: 24 April 2022) and was conducted in accordance with the Declaration of Helsinki (ethical principles for medical research involving human subjects). Informed consent was obtained from all participants or their legal guardians. Written informed consent was obtained from all subjects and\/or their legal guardians to contribute to our study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1158"}}