{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:23:47Z","timestamp":1791527027363,"version":"4.3.4"},"reference-count":75,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-33\/2026-03\/200161"],"award-info":[{"award-number":["451-03-33\/2026-03\/200161"]}]},{"name":"the Ministry of Science, Technological Development, and Innovation of the Republic of Serbia","award":["451-03-34\/2026-03\/200161"],"award-info":[{"award-number":["451-03-34\/2026-03\/200161"]}]},{"award":["451-03-33\/2026-03\/200161"],"award-info":[{"award-number":["451-03-33\/2026-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]},{"award":["451-03-34\/2026-03\/200161"],"award-info":[{"award-number":["451-03-34\/2026-03\/200161"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Although COVID-19 is generally more severe in males, data on sex-specific differences in the predictive value of commonly used inflammatory biomarkers remain limited. The study aimed to evaluate the sex-specific prognostic performance of selected biomarkers during the Alpha variant wave. Methods: In single-center study, univariate and multivariable regressions analyses, along with receiver operating characteristic curve (ROC) analyses, were performed to assess the association of acute-phase proteins, cytokines, and white blood cell indices (at admission and 7 days later) and disease severity and mortality in patients with severe-to-critical COVID-19. Results: At admission, the combined assessment of ferritin and D-dimer predicted disease severity in both sexes; however, optimal cut-off values and diagnostic performance (specificity and sensitivity) differed between males and females. In males, neutrophil and lymphocyte counts provided additional clinically relevant predictive value. Seven days after admission, the combination of ferritin, D-dimer, and fibrinogen in males, and ferritin, as an independent predictor within a model including lactate dehydrogenase, in females demonstrated strong predictive performance for severe-to-critical COVID-19. At this time-point, lymphocyte count in males was also identified as an independent predictor of disease severity. Notably, C-reactive protein and neutrophil count correlated with mortality in males with severe-to-critical disease. Conclusions: Severe COVID-19 is predicted by distinct acute-phase proteins and shared, sex-specific biomarkers, but with distinct cut-offs and predictive accuracy. In males, white blood cell indices also serve as independent predictors. Furthermore, prognostic utility changes of these biomarkers over the course of the disease, suggesting sex-specific and time-dependent role in COVID-19 pathogenesis.<\/jats:p>","DOI":"10.3390\/medsci14020282","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:01Z","timestamp":1780333861000},"page":"282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex-Specific Signatures of Circulating Protein and Cellular Host Responses Predicting COVID-19 Severity"],"prefix":"10.3390","volume":"14","author":[{"given":"Milica","family":"Radisavljevi\u0107","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Belgrade\u2014Faculty of Pharmacy, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zorica","family":"Stoji\u0107-Vukani\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Belgrade\u2014Faculty of Pharmacy, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijana","family":"Kosanovi\u0107","sequence":"additional","affiliation":[{"name":"Radiology Department, University Hospital \u201cDr Dragi\u0161a Mi\u0161ovi\u0107-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-6114","authenticated-orcid":false,"given":"Miodrag","family":"Lalo\u0161evi\u0107","sequence":"additional","affiliation":[{"name":"Radiology Department, University Hospital \u201cDr Dragi\u0161a Mi\u0161ovi\u0107-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8418-4238","authenticated-orcid":false,"given":"Iva","family":"Perovi\u0107 Blagojevi\u0107","sequence":"additional","affiliation":[{"name":"Department for Laboratory Diagnostic, University Hospital \u201cDr Dragi\u0161a Mi\u0161ovi\u0107-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"Miliji\u0107 Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Laboratory Diagnostic, University Hospital \u201cDr Dragi\u0161a Mi\u0161ovi\u0107-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksa","family":"Petkovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Laboratory Diagnostic, University Hospital \u201cDr Dragi\u0161a Mi\u0161ovi\u0107-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Marjanovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Laboratory Diagnostic, University Hospital \u201cDr Dragi\u0161a Mi\u0161ovi\u0107-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-7716","authenticated-orcid":false,"given":"Gordana","family":"Leposavi\u0107","sequence":"additional","affiliation":[{"name":"Independent Researcher, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.5694\/mja2.50698","article-title":"Clinical presentation and management of COVID-19","volume":"213","author":"Thevarajan","year":"2020","journal-title":"Med. J. Aust."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_3","unstructured":"World Health Organization (2026, April 04). Listing of WHO\u2019s Response to COVID-19, Available online: https:\/\/www.who.int\/news\/item\/29-06-2020-covidtimeline."},{"key":"ref_4","unstructured":"UN News (2026, April 04). WHO Chief Declares End to COVID-19 as a Global Health Emergency, Available online: https:\/\/news.un.org\/en\/story\/2023\/05\/1136367."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2632010X241228053","DOI":"10.1177\/2632010X241228053","article-title":"The WHO has Declared COVID-19 is No Longer a Pandemic-Level Threat: A Perspective Evaluating Potential Public Health Impacts","volume":"17","author":"Roknuzzaman","year":"2024","journal-title":"Clin. Pathol."},{"key":"ref_6","unstructured":"KFF (2024). Global COVID-19 Tracker, KFF. Available online: https:\/\/www.kff.org\/covid-19\/global-covid-19-tracker\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41579-022-00722-z","article-title":"Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity","volume":"20","author":"Markov","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lu, J., Hu, S., Fan, R., Liu, Z., Yin, X., Wang, Q., Lv, Q., Cai, Z., Li, H., and Hu, Y. (2020). ACP risk grade: A simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan in China. medRxiv.","DOI":"10.1101\/2020.02.20.20025510"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12967-020-02374-0","article-title":"Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage","volume":"18","author":"Liu","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_10","first-page":"e9575","article-title":"Poor prognostic biochemical markers predicting fatalities caused by COVID-19: A retrospective observational study from a developing country","volume":"12","author":"Asghar","year":"2020","journal-title":"Cureus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"720","DOI":"10.4103\/jfmpc.jfmpc_1326_24","article-title":"Inflammatory biomarkers and adverse outcome in COVID-19: Prelude for future viral pandemics","volume":"14","author":"Kumar","year":"2025","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, D., Li, R., Wang, J., Jiang, Q., Gao, C., Yang, J., Ge, L., and Hu, Q. (2020). Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: A descriptive study. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-05242-w"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/s41374-020-0431-6","article-title":"Retrospective analysis of laboratory testing in 54 patients with severe-or critical-type 2019 novel coronavirus pneumonia","volume":"100","author":"Li","year":"2020","journal-title":"Lab. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4103\/bbrj.bbrj_188_20","article-title":"Serum levels of interleukin-6, ferritin, C-reactive protein, lactate dehydrogenase, D-dimer, and count of lymphocytes and neutrophils in COVID-19 patients: Its correlation to the disease severity","volume":"5","author":"Kadhim","year":"2021","journal-title":"Biomed. Biotechnol. Res. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.4103\/jfmpc.jfmpc_423_23","article-title":"Role of biomarkers in prognostication of moderate and severe COVID-19 cases","volume":"12","author":"Pal","year":"2023","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39003","DOI":"10.1038\/s41598-025-24173-7","article-title":"Role of immune-inflammatory biomarkers and their derived ratio in predicting COVID-19 severity and mortality","volume":"15","author":"Taha","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_17","first-page":"131","article-title":"Utility of Biochemical Markers in Predicting Severe COVID-19: Experience from a Tertiary Hospital in South India","volume":"33","author":"Shenoy","year":"2022","journal-title":"Electron. J. Int. Fed. Clin. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1001\/jamainternmed.2020.3539","article-title":"Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy","volume":"180","author":"Grasselli","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"m1966","DOI":"10.1136\/bmj.m1966","article-title":"Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: Prospective cohort study","volume":"369","author":"Petrilli","year":"2020","journal-title":"BMJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1001\/jamainternmed.2020.3596","article-title":"Factors associated with death in critically ill patients with coronavirus disease 2019 in the US","volume":"180","author":"Gupta","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_21","unstructured":"World Health Organization (2026, April 04). Diagnostic Testing for SARS-CoV-2: Interim Guidance, Available online: https:\/\/iris.who.int\/server\/api\/core\/bitstreams\/7caa3b48-f99b-4cc2-b0f3-a954da4060d7\/content."},{"key":"ref_22","unstructured":"National Institutes of Health (2026, April 04). Coronavirus Disease 2019 (COVID-19) Treatment Guidelines, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK570371\/pdf\/Bookshelf_NBK570371.pdfz."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3892\/br.2024.1788","article-title":"Time-dependent ROC curve analysis to determine the predictive capacity of seven clinical scales for mortality in patients with COVID-19: Study of a hospital cohort with very high mortality","volume":"20","year":"2024","journal-title":"Biomed. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_25","unstructured":"World Health Organization (2026, April 04). Clinical Management of COVID-19, Available online: https:\/\/www.who.int\/teams\/health-care-readiness\/covid-19."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cruciata, A., Volpicelli, L., Di Bari, S., Iaiani, G., Cirillo, B., Pugliese, F., Pellegrino, D., Galardo, G., and Taliani, G. (2022). Risk of Seven-Day Worsening and Death: A New Clinically Derived COVID-19 Score. Viruses, 14.","DOI":"10.3390\/v14030642"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1055\/s-0037-1613124","article-title":"A performance evaluation of commercial fibrinogen reference preparations and assays for Clauss and PT-derived fibrinogen","volume":"87","author":"Mackie","year":"2002","journal-title":"Thromb. Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S0895-4356(96)00236-3","article-title":"A simulation study of the number of events per variable in logistic regression analysis","volume":"49","author":"Peduzzi","year":"1996","journal-title":"J. Clin. Epidemiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/aje\/kwk052","article-title":"Relaxing the rule of ten events per variable in logistic and Cox regression","volume":"165","author":"Vittinghoff","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1093\/clinchem\/41.8.1248","article-title":"Multivariate Receiver-Operating Characteristic Curve Analysis: Prostate cancer screening as example","volume":"41","author":"Shultz","year":"1995","journal-title":"Clin. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4097\/kja.21209","article-title":"Receiver operating characteristic curve: Overview and practical use for clinicians","volume":"75","author":"Nahm","year":"2022","journal-title":"Korean J. Anesthesiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13605","DOI":"10.1038\/s41598-024-64384-y","article-title":"Serum cytokine dysregulation signatures associated with COVID-19 outcomes in high mortality intensive care unit cohorts across pandemic waves and variants","volume":"14","author":"Bloos","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Canon-Estrada, J.A., Munoz-Ordonez, M.A., Escalante-Forero, M., Rodas, Y., Arteaga-Tobar, A.A., Azcarate-Rodriguez, V., Perna, E., Mendoza, I., Wyss, F., and Barisani, J.L. (2025). Biochemical differences based on sex and clusters of biomarkers in patients with COVID-19: Analysis from the CARDIO COVID 19\u201320 registry. BMC Cardiovasc. Disord., 25.","DOI":"10.1186\/s12872-025-04565-3"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.jinf.2020.09.006","article-title":"Serum Ferritin is an independent risk factor for Acute Respiratory Distress Syndrome in COVID-19","volume":"81","author":"Gandini","year":"2020","journal-title":"J. Infect."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.jinf.2020.10.012","article-title":"Sex-disaggregated data confirm serum ferritin as an independent predictor of disease severity both in male and female COVID-19 patients","volume":"82","author":"Gandini","year":"2021","journal-title":"J. Infect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e12421","DOI":"10.15252\/emmm.202012421","article-title":"The role of interleukin-6 in monitoring severe case of coronavirus disease 2019","volume":"12","author":"Liu","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_38","first-page":"14","article-title":"Ferritin\u2014Severity predictor in patients with multisystem inflammatory syndrome","volume":"7","author":"Rurua","year":"2025","journal-title":"Georgian Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13293-021-00410-2","article-title":"Sex differences in the immune response to acute COVID-19 respiratory tract infection","volume":"12","author":"Qi","year":"2021","journal-title":"Biol. Sex. Differ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/intimm\/dxx031","article-title":"Hyperferritinemia and inflammation","volume":"29","author":"Kernan","year":"2017","journal-title":"Int. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jahan, H., Yeasmin, T., and Roy, M. (2022). Elevated D-dimers associated with severity of COVID-19: A systematic review and meta-analysis. Med. Res. Arch., 10.","DOI":"10.18103\/mra.v10i7.2870"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1055\/s-0043-1770365","article-title":"D-dimer in Coronavirus 2019: An Acute Phase Reactant?","volume":"50","year":"2024","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_43","first-page":"e70682","article-title":"D-dimer as a Predictor of ICU Admission and Mortality in COVID-19 Patients: Insights From a Two-Year Retrospective Study From a Tertiary Care Center in South India","volume":"16","author":"Stephen","year":"2024","journal-title":"Cureus"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1055\/s-2005-922485","article-title":"Fibrin D-dimer and cardiovascular risk","volume":"5","author":"Lowe","year":"2005","journal-title":"Semin. Vasc. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1111\/bjh.16907","article-title":"Re: The source of elevated plasma D-dimer levels in COVID-19 infection","volume":"190","author":"Hunt","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1182\/blood.2020006000","article-title":"COVID-19 and its implications for thrombosis and anticoagulation","volume":"135","author":"Connors","year":"2020","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.thromres.2013.09.033","article-title":"Age and sex-dependent reference intervals for D-dimer: Evidence for a marked increase by age","volume":"132","author":"Haase","year":"2013","journal-title":"Thromb. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s11739-011-0608-5","article-title":"Age and gender specific cut-off values to improve the performance of D-dimer assays to predict the risk of venous thromboembolism recurrence","volume":"8","author":"Legnani","year":"2013","journal-title":"Intern. Emerg. Med."},{"key":"ref_49","first-page":"1","article-title":"Comparison of D-dimer level measured on the third day of hospitalization with admission D-dimer level in predicting in-hospital mortality in COVID-19 patients","volume":"36","author":"Selcuk","year":"2021","journal-title":"Medeni. Med. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6124","DOI":"10.1002\/cam4.1820","article-title":"Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy","volume":"7","author":"Feng","year":"2018","journal-title":"Cancer Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.hrtlng.2022.10.012","article-title":"Sex differences in the prognostic value of troponin and D-dimer in COVID-19 illness","volume":"58","author":"Mukhopadhyay","year":"2023","journal-title":"Heart Lung"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e11711","DOI":"10.1590\/1414-431x2021e11711","article-title":"Why do men have worse COVID-19-related outcomes?","volume":"55","author":"Sassi","year":"2022","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10","DOI":"10.46439\/allergy.3.031","article-title":"Why are men more severely affected by COVID-19?","volume":"3","author":"Alam","year":"2022","journal-title":"J. Allergy Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s12288-016-0683-x","article-title":"Role of Plasma Fibrinogen in Diagnosis and Prediction of Short Term Outcome in Neonatal Sepsis","volume":"33","author":"Mitra","year":"2017","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10760296221101386","DOI":"10.1177\/10760296221101386","article-title":"Decreasing Plasma Fibrinogen Levels in the Intensive Care Unit Are Associated with High Mortality Rates In Patients With Sepsis-Induced Coagulopathy","volume":"28","author":"Mori","year":"2022","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1002\/jmv.26137","article-title":"Gendered effects on inflammation reaction and outcome of COVID-19 patients in Wuhan","volume":"92","author":"Qin","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sheriff, A., Kayser, S., Brunner, P., and Vogt, B. (2021). C-Reactive Protein Triggers Cell Death in Ischemic Cells. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.630430"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"El Azhary, K., Ghazi, B., Kouhen, F., El Bakkouri, J., Chamlal, H., El Ghanmi, A., and Badou, A. (2025). Clinical Impact of Neutrophil Variation on COVID-19 Complications. Diagnostics, 15.","DOI":"10.3390\/diagnostics15040457"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ijid.2020.04.086","article-title":"Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis","volume":"96","author":"Zhao","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.5114\/aoms.2020.99006","article-title":"Reduction of lymphocyte count at early stage elevates severity and death risk of COVID-19 patients: A hospital-based case-cohort study","volume":"19","author":"Fei","year":"2023","journal-title":"Arch. Med. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"448","DOI":"10.14740\/jocmr4240","article-title":"Use of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in COVID-19","volume":"12","author":"Chan","year":"2020","journal-title":"J. Clin. Med. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s12931-020-01428-7","article-title":"Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19","volume":"21","author":"Ye","year":"2020","journal-title":"Respir. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Nikkhoo, B., Mohammadi, M., Hasani, S., Sigari, N., Borhani, A., Ramezani, C., Charajoo, A., Badri, S., Rostami, F., and Etemadi, M. (2023). Elevated Interleukin (IL)-6 as a Predictor of Disease Severity among COVID-19 Patients: A prospective cohort study. BMC Infect. Dis., 23.","DOI":"10.1186\/s12879-023-08294-w"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2003006","DOI":"10.1183\/13993003.03006-2020","article-title":"Confronting the controversy: Interleukin-6 and the COVID-19 cytokine storm syndrome","volume":"56","author":"Chen","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.pcd.2021.05.002","article-title":"The sex-related discrepancy in laboratory parameters of severe COVID-19 patients with diabetes: A retrospective cohort study","volume":"15","author":"Hammad","year":"2021","journal-title":"Prim. Care Diabetes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1177\/00033197211070884","article-title":"Sex Difference in the Association Between Neutrophil to Lymphocyte Ratio and Severity of Coronary Artery Disease","volume":"73","author":"Pan","year":"2022","journal-title":"Angiology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2459\/JCM.0000000000001261","article-title":"Sex-related differences in patients with coronavirus disease 2019: Results of the Cardio-COVID-Italy multicentre study","volume":"23","author":"Lombardi","year":"2022","journal-title":"J. Cardiovasc. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1080\/23744235.2022.2055786","article-title":"Inflammation parameters predict fatal outcome in male COVID-19 patients in a low case-fatality area\u2014A population-based registry study","volume":"54","author":"Forsblom","year":"2022","journal-title":"Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/s41586-020-2700-3","article-title":"Sex differences in immune responses that underlie COVID-19 disease outcomes","volume":"588","author":"Takahashi","year":"2020","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Montano, L., Donato, F., Bianco, P.M., Lettieri, G., Guglielmino, A., Motta, O., Bonapace, I.M., and Piscopo, M. (2021). Air pollution and COVID-19: A possible dangerous synergy for male fertility. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18136846"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"37031","DOI":"10.1007\/s11356-021-14579-x","article-title":"Semen quality as a potential susceptibility indicator to SARS-CoV-2 insults in polluted areas","volume":"28","author":"Montano","year":"2021","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1126\/science.abe7199","article-title":"Sex differences in immune responses","volume":"371","author":"Takahashi","year":"2021","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"McKenna, E., Wubben, R., Isaza-Correa, J.M., Melo, A.M., Mhaonaigh, A.U., Conlon, N., O\u2019Donnell, J.S., N\u00ed Cheallaigh, C., Hurley, T., and Stevenson, N.J. (2022). Neutrophils in COVID-19: Not innocent bystanders. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.864387"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00428-020-02886-6","article-title":"Pulmonary Pathology and COVID-19: Lessons From Autopsy. The Experience of European Pulmonary Pathologists","volume":"477","author":"Calabrese","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s11239-020-02324-z","article-title":"Neutrophil Extracellular Traps and Thrombosis in COVID-19","volume":"51","author":"Zuo","year":"2021","journal-title":"J. Thromb. Thrombolysis"}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/282\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:25:34Z","timestamp":1780575934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/2\/282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,31]]},"references-count":75,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["medsci14020282"],"URL":"https:\/\/doi.org\/10.3390\/medsci14020282","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,31]]}}}