{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:00:19Z","timestamp":1780452019921,"version":"3.54.1"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003827","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["2020-1.1.6-J\u00d6V\u0150-2021-00012"],"award-info":[{"award-number":["2020-1.1.6-J\u00d6V\u0150-2021-00012"]}],"id":[{"id":"10.13039\/501100003827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003827","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["2021\u20132027"],"award-info":[{"award-number":["2021\u20132027"]}],"id":[{"id":"10.13039\/501100003827","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003827","name":"National Research, Development and Innovation Office","doi-asserted-by":"publisher","award":["101136957"],"award-info":[{"award-number":["101136957"]}],"id":[{"id":"10.13039\/501100003827","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Horizon Europe\u2014Research Framework Programme","award":["2020-1.1.6-J\u00d6V\u0150-2021-00012"],"award-info":[{"award-number":["2020-1.1.6-J\u00d6V\u0150-2021-00012"]}]},{"name":"Horizon Europe\u2014Research Framework Programme","award":["2021\u20132027"],"award-info":[{"award-number":["2021\u20132027"]}]},{"name":"Horizon Europe\u2014Research Framework Programme","award":["101136957"],"award-info":[{"award-number":["101136957"]}]},{"DOI":"10.13039\/501100000780","name":"Comorbidity Mechanisms Utilized In Healthcare (COMMUTE)","doi-asserted-by":"publisher","award":["2020-1.1.6-J\u00d6V\u0150-2021-00012"],"award-info":[{"award-number":["2020-1.1.6-J\u00d6V\u0150-2021-00012"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"Comorbidity Mechanisms Utilized In Healthcare (COMMUTE)","doi-asserted-by":"publisher","award":["2021\u20132027"],"award-info":[{"award-number":["2021\u20132027"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"Comorbidity Mechanisms Utilized In Healthcare (COMMUTE)","doi-asserted-by":"publisher","award":["101136957"],"award-info":[{"award-number":["101136957"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vaccines played a crucial role in the COVID-19 pandemic, but their long-term biological effects and efficacy in vulnerable populations remain under intensive investigation. This study assessed clinical outcomes, comorbidities, and systemic biomarker and proteomic profiles in 366 multimorbid patients, stratified into four groups based on SARS-CoV-2 infection and vaccination status (COV+ vac+, COV+ vac\u2212, COV\u2212 vac+, COV\u2212 vac\u2212). Clinical and laboratory data, including comorbidities and relevant biomarkers, were collected. Proteomic analysis using mass spectrometry was performed to identify molecular changes associated with infection and vaccination. Statistical analyses examined associations between clinical status, biomarkers, and patient outcomes. As most participants received mRNA-based vaccines, the results primarily reflect responses to spike protein-expressing platforms. Biomarkers of cardiac and renal stress\u2014namely proBNP and carbamide\u2014were elevated in vaccinated individuals. Five deaths occurred in the COV+ vac+ group and two in the COV+ vac\u2212 group, most of which were attributed to exacerbations of pre-existing chronic diseases rather than to COVID-19 pneumonia. Protection against breakthrough infections waned over time, particularly beyond 200 days post-vaccination. Mass spectrometry identified proteins such as actin, fibrinogen chains, and SAA2 as potential diagnostic targets. Although the cross-sectional observational design limits the ability to draw causal inferences, the observed waning immunity and potential systemic alterations in vaccinated multimorbid patients highlight the importance of longitudinal follow-up to guide tailored immunization strategies and post-vaccination monitoring in high-risk groups.<\/jats:p>","DOI":"10.3390\/ijms26168007","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T13:08:51Z","timestamp":1755608931000},"page":"8007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical and Proteomic Associations of SARS-CoV-2 Infection and COVID-19 Vaccination in Multimorbid Patients: A Cross-Sectional Observational Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6294-5345","authenticated-orcid":false,"given":"Anett","family":"Hud\u00e1k","sequence":"first","affiliation":[{"name":"Pharmacoidea Ltd., H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alad\u00e1r","family":"Pettko-Szandtner","sequence":"additional","affiliation":[{"name":"Biological Research Centre of the Hungarian Academy of Sciences, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annam\u00e1ria","family":"Letoha","sequence":"additional","affiliation":[{"name":"Albert Szent-Gy\u00f6rgyi Clinical Center, Department of Medicine, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6035-4009","authenticated-orcid":false,"given":"Tam\u00e1s","family":"Letoha","sequence":"additional","affiliation":[{"name":"Pharmacoidea Ltd., H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","article-title":"SARS-CoV-2 pathogenesis","volume":"20","author":"Lamers","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105924","DOI":"10.1016\/j.ijantimicag.2020.105924","article-title":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges","volume":"55","author":"Lai","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_3","unstructured":"Cascella, M., Rajnik, M., Aleem, A., Dulebohn, S.C., and Di Napoli, R. (2024). Features, Evaluation, and Treatment of Coronavirus (COVID-19). StatPearls, StatPearls Publishing."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Borczuk, A.C., and Yantiss, R.K. (2022). The pathogenesis of coronavirus-19 disease. J. Biomed. Sci., 29.","DOI":"10.1186\/s12929-022-00872-5"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.pmr.2023.03.003","article-title":"Cardiovascular Complications of Coronavirus Disease-2019","volume":"34","author":"Terzic","year":"2023","journal-title":"Phys. Med. Rehabil. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/jmv.26232","article-title":"The cytokine storm and COVID-19","volume":"93","author":"Hu","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_7","first-page":"162","article-title":"SARS-CoV-2 variant biology: Immune escape, transmission and fitness","volume":"21","author":"Carabelli","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hussein, H.A., Hassan, R.Y.A., Chino, M., and Febbraio, F. (2020). Point-of-Care Diagnostics of COVID-19: From Current Work to Future Perspectives. Sensors, 20.","DOI":"10.3390\/s20154289"},{"key":"ref_9","first-page":"1","article-title":"Biomarkers of COVID-19 and technologies to combat SARS-CoV-2","volume":"2","author":"Zhang","year":"2020","journal-title":"Adv. Biomark. Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.molimm.2023.03.009","article-title":"Mechanistic insight into the protective and pathogenic immune-responses against SARS-CoV-2","volume":"156","author":"Purbey","year":"2023","journal-title":"Mol. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e35570","DOI":"10.1016\/j.heliyon.2024.e35570","article-title":"Unravelling the complex interplay of age, comorbidities, and multimorbidities in COVID-19 disease progression: Clinical implications and future perspectives","volume":"10","author":"Shoukat","year":"2024","journal-title":"Heliyon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"339385","DOI":"10.1016\/j.aca.2021.339385","article-title":"Mass spectrometry applied to diagnosis, prognosis, and therapeutic targets identification for the novel coronavirus SARS-CoV-2: A review","volume":"1195","author":"Lima","year":"2022","journal-title":"Anal. Chim. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2174\/1874357920130927003","article-title":"Application of maldi-tof mass spectrometry in clinical virology: A review","volume":"7","author":"Cobo","year":"2013","journal-title":"Open Virol. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cristina G\u00f3mez Camarasa, F.C. (2018). Application of MALDI-TOF Mass Spectrometry in Clinical Virology. The Use of Mass Spectrometry Technology (MALDI-TOF) in Clinical Microbiology, Academic Press.","DOI":"10.1016\/B978-0-12-814451-0.00012-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107912","DOI":"10.1016\/j.ijid.2025.107912","article-title":"Impact of pre-existing comorbidities and multimorbidities, demography and viral variants on post-acute sequelae of COVID-19 (\u2018Long COVID\u2019) in Dutch primary care: A retrospective cohort study","volume":"156","author":"Berends","year":"2025","journal-title":"Int. J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Justiz-Vaillant, A., Roopnarine, K., Solomon, S., Phillips, A., Sandy, S., Subero, A., Seepersad, S., Span, N., Ramnath, P., and Ramnarine, A. (2025). COVID-19 Vaccines Effectiveness and Safety in Trinidad and Tobago: A Systematic Review and Meta-Analysis. Microorganisms, 13.","DOI":"10.3390\/microorganisms13010135"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bhattacharjee, B., Lu, P., Monteiro, V.S., Tabachnikova, A., Wang, K., Hooper, W.B., Bastos, V., Greene, K., Sawano, M., and Guirgis, C. (2025). Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination. medRxiv.","DOI":"10.1101\/2025.02.18.25322379"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mundorf, A.K., Semmler, A., Heidecke, H., Schott, M., Steffen, F., Bittner, S., Lackner, K.J., Schulze-Bosse, K., Pawlitzki, M., and Meuth, S.G. (2024). Clinical and Diagnostic Features of Post-Acute COVID-19 Vaccination Syndrome (PACVS). Vaccines, 12.","DOI":"10.20944\/preprints202406.0848.v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/ane.13550","article-title":"Neurological side effects of SARS-CoV-2 vaccinations","volume":"145","author":"Finsterer","year":"2022","journal-title":"Acta Neurol. Scand."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/CRD.0000000000000330","article-title":"Elevated D-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019: A Systematic Review and Meta-Analysis","volume":"28","author":"Shah","year":"2020","journal-title":"Cardiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1056\/NEJMoa054444","article-title":"D-dimer testing to determine the duration of anticoagulation therapy","volume":"355","author":"Palareti","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.autrev.2007.01.016","article-title":"Ferritin in autoimmune diseases","volume":"6","author":"Shoenfeld","year":"2007","journal-title":"Autoimmun. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102778","DOI":"10.1016\/j.jaut.2021.102778","article-title":"Ferritin\u2014From iron, through inflammation and autoimmunity, to COVID-19","volume":"126","author":"Mahroum","year":"2022","journal-title":"J. Autoimmun."},{"key":"ref_24","first-page":"e14642","article-title":"Application of CALL score for prediction of progression risk in patients with COVID-19 at university hospital in Turkey","volume":"75","author":"Ilgin","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_25","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_26","first-page":"1035","article-title":"How we manage a high D-dimer","volume":"109","author":"Franchini","year":"2024","journal-title":"Haematologica"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cao, Z., Jia, Y., and Zhu, B. (2019). BNP and NT-proBNP as Diagnostic Biomarkers for Cardiac Dysfunction in Both Clinical and Forensic Medicine. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081820"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/clc.22883","article-title":"NT-proBNP is associated with mortality and adverse cardiac events in patients with atrial fibrillation presenting to the emergency department","volume":"41","author":"Holl","year":"2018","journal-title":"Clin. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/ejhf.1494","article-title":"Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations","volume":"21","author":"Mueller","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1016\/j.bbadis.2012.12.014","article-title":"Biomarkers and diagnostics in heart failure","volume":"1832","author":"Gaggin","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/ejhf.2095","article-title":"Characterization of NT-proBNP in a large cohort of COVID-19 patients","volume":"23","author":"Rey","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.34172\/jcvtr.2021.26","article-title":"Prognostic significance of N-Terminal Pro-BNP in patients with COVID-19 pneumonia without previous history of heart failure","volume":"13","author":"Selcuk","year":"2021","journal-title":"J. Cardiovasc. Thorac. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12931-020-01352-w","article-title":"Prognostic value of NT-proBNP in patients with severe COVID-19","volume":"21","author":"Gao","year":"2020","journal-title":"Respir. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41591-021-01630-0","article-title":"Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection","volume":"28","author":"Patone","year":"2022","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41541-024-00893-1","article-title":"Myocarditis associated with COVID-19 vaccination","volume":"9","author":"Buoninfante","year":"2024","journal-title":"NPJ Vaccines"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Robles, J.P., Zamora, M., Adan-Castro, E., Siqueiros-Marquez, L., Martinez de la Escalera, G., and Clapp, C. (2022). The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin alpha5beta1 and NF-kappaB signaling. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.101695"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1007\/s10753-024-02208-x","article-title":"Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells","volume":"48","author":"Gultom","year":"2025","journal-title":"Inflammation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.tim.2023.06.004","article-title":"SARS-CoV-2 and the spike protein in endotheliopathy","volume":"32","author":"Perico","year":"2024","journal-title":"Trends Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Panigrahi, S., Goswami, T., Ferrari, B., Antonelli, C.J., Bazdar, D.A., Gilmore, H., Freeman, M.L., Lederman, M.M., and Sieg, S.F. (2021). SARS-CoV-2 Spike Protein Destabilizes Microvascular Homeostasis. Microbiol. Spectr., 9.","DOI":"10.1128\/Spectrum.00735-21"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, D., He, W., Yu, B., Wang, D.W., and Ni, L. (2024). NT-proBNP ratio is a potential predictor for COVID-19 outcomes in adult Chinese patients: A retrospective study. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-56329-2"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000329537","article-title":"Elevated Levels of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Chronic Dyspnea and Moderate Renal Dysfunction: Decreased Clearance or Increased Cardiac Stress","volume":"1","author":"Wieshammer","year":"2011","journal-title":"Cardiorenal Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1309\/AJCP60HTPGIGFCNK","article-title":"The effect of renal dysfunction on BNP, NT-proBNP, and their ratio","volume":"133","author":"Srisawasdi","year":"2010","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41590-024-01754-8","article-title":"Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19","volume":"25","author":"Hanson","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_44","first-page":"83","article-title":"Hyperferritinemia in autoimmunity","volume":"10","author":"Shoenfeld","year":"2008","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1089\/vim.2023.0094","article-title":"Bioinformation Analysis of Differential Expression Proteins in Different Processes of COVID-19","volume":"37","author":"Guo","year":"2024","journal-title":"Viral Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6318","DOI":"10.1080\/21655979.2021.1971037","article-title":"Potential biomarkers: Differentially expressed proteins of the extrinsic coagulation pathway in plasma samples from patients with depression","volume":"12","author":"Yu","year":"2021","journal-title":"Bioengineered"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cabrera, L.E., Jokiranta, S.T., Maki, S., Miettinen, S., Kant, R., Kareinen, L., Sironen, T., Pietila, J.P., Kantele, A., and Kekalainen, E. (2024). The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012368"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s10020-018-0047-0","article-title":"Serum amyloid A\u2014A review","volume":"24","author":"Sack","year":"2018","journal-title":"Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.semnephrol.2013.08.001","article-title":"Overview of complement activation and regulation","volume":"33","author":"Noris","year":"2013","journal-title":"Semin. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kim, A.H.J., Wu, X., and Atkinson, J.P. (2020). The beneficial and pathogenic roles of complement in COVID-19. Cleve Clin. J. Med.","DOI":"10.3949\/ccjm.87a.ccc065"},{"key":"ref_51","first-page":"1454","article-title":"Activated neutrophils in the initiation and progression of COVID-19: Hyperinflammation and immunothrombosis in COVID-19","volume":"14","author":"Zhao","year":"2022","journal-title":"Am. J. Transl. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"ofac427","DOI":"10.1093\/ofid\/ofac427","article-title":"Impact of Innate Immunity, Endothelial Damage, and Metabolic Biomarkers on COVID-19 Severity and Mortality","volume":"9","author":"Rocco","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sulimai, N.H., Brown, J., and Lominadze, D. (2022). Fibrinogen, Fibrinogen-like 1 and Fibrinogen-like 2 Proteins, and Their Effects. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071712"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.thromres.2017.11.016","article-title":"Variants in chondroitin sulfate metabolism genes in thrombotic storm","volume":"161","author":"Nuytemans","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/j.1538-7836.2007.02516.x","article-title":"Serpins in thrombosis, hemostasis and fibrinolysis","volume":"5","author":"Rau","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"118","DOI":"10.4103\/0975-7406.76489","article-title":"Acute-phase proteins: As diagnostic tool","volume":"3","author":"Jain","year":"2011","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1631\/jzus.2005.B1045","article-title":"Acute phase reaction and acute phase proteins","volume":"6","author":"Gruys","year":"2005","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/bs.acc.2019.01.002","article-title":"Chapter Two\u2014Acute phase reactant serum amyloid A in inflammation and other diseases","volume":"Volume 90","author":"Makowski","year":"2019","journal-title":"Advances in Clinical Chemistry"},{"key":"ref_59","unstructured":"Bardhan, M., and Kaushik, R. (2025). Physiology, Complement Cascade. StatPearls, StatPearls Publishing."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"103896","DOI":"10.1016\/j.jprot.2020.103896","article-title":"Novel biomarkers in cats with congestive heart failure due to primary cardiomyopathy","volume":"226","author":"Liu","year":"2020","journal-title":"J. Proteomics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1001\/jama.1979.03300070017016","article-title":"Blood resource management","volume":"242","author":"Henry","year":"1979","journal-title":"JAMA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0022-1759(92)90313-I","article-title":"Measuring cytokine levels in blood. Importance of anticoagulants, processing, and storage conditions","volume":"153","author":"Thavasu","year":"1992","journal-title":"J. Immunol. Methods"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1093\/cid\/ciaa414","article-title":"Prediction for Progression Risk in Patients With COVID-19 Pneumonia: The CALL Score","volume":"71","author":"Ji","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lang, L., Pettko-Szandtner, A., Tuncay Elbasi, H., Takatsuka, H., Nomoto, Y., Zaki, A., Dorokhov, S., De Jaeger, G., Eeckhout, D., and Ito, M. (2021). The DREAM complex represses growth in response to DNA damage in Arabidopsis. Life Sci. Alliance, 4.","DOI":"10.26508\/lsa.202101141"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-1-60761-444-9_5","article-title":"Target-decoy search strategy for mass spectrometry-based proteomics","volume":"604","author":"Elias","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jprot.2016.05.032","article-title":"A multi-model statistical approach for proteomic spectral count quantitation","volume":"144","author":"Branson","year":"2016","journal-title":"J. Proteom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8007\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:30:58Z","timestamp":1760034658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":66,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26168007"],"URL":"https:\/\/doi.org\/10.3390\/ijms26168007","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,19]]}}}