{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:50:46Z","timestamp":1765547446710,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Sepsis causes millions of deaths each year. Rapid, targeted therapy can reduce mortality rates. Both bacterial and viral pathogens can trigger sepsis, but the utility of commonly used inflammatory markers for differentiation remains controversial. Moreover, little is known about the time courses of alternative inflammatory parameters. The aim of this prospective, two-center observational study was to investigate the differences in the course of soluble Neuropilin-1 (sNRP-1) levels between bacterial and viral sepsis over a 7-day period. To be included, adult patients had to meet the SEPSIS-3 criteria and be diagnosed with either a bacterial or viral pathogen. Immunosuppressed patients were excluded. While IL-6, PCT, and CRP levels decreased consistently over time, sNRP-1 levels remained elevated in the bacterial group throughout the entire ICU stay. PCT (p &lt; 0.001) and CRP (p = 0.016) levels were significantly associated with the course of sNRP-1. The AUC of sNRP-1 was 0.777 for discriminating between bacterial and viral infections on day 1. sNRP-1 remained stable and significantly higher in bacterial than in viral infections. Furthermore, the AUC values for discrimination ranged from acceptable to good, depending on the day of the ICU stay. sNRP-1 may serve as a potential tool to differentiate between bacterial and viral pathogens in sepsis.<\/jats:p>","DOI":"10.3390\/v17070997","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T14:13:43Z","timestamp":1752761623000},"page":"997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Soluble Neuropilin-1 as a Marker for Distinguishing Bacterial and Viral Sepsis in Critically Ill Patients\u2014A Prospective, Multicenter, Observational Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0677-8756","authenticated-orcid":false,"given":"Fabian","family":"Perschinka","sequence":"first","affiliation":[{"name":"Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg Franz","family":"Lehner","sequence":"additional","affiliation":[{"name":"Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7645-1252","authenticated-orcid":false,"given":"Timo","family":"Mayerh\u00f6fer","sequence":"additional","affiliation":[{"name":"Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2835-5263","authenticated-orcid":false,"given":"Frank","family":"Hartig","sequence":"additional","affiliation":[{"name":"Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3010-1055","authenticated-orcid":false,"given":"Birgit","family":"Zassler","sequence":"additional","affiliation":[{"name":"Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0152-0975","authenticated-orcid":false,"given":"Johannes","family":"B\u00f6sch","sequence":"additional","affiliation":[{"name":"Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-4214","authenticated-orcid":false,"given":"Dietmar","family":"Fries","sequence":"additional","affiliation":[{"name":"Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-3258","authenticated-orcid":false,"given":"Romuald","family":"Bellmann","sequence":"additional","affiliation":[{"name":"Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-0881","authenticated-orcid":false,"given":"Michael","family":"Joannidis","sequence":"additional","affiliation":[{"name":"Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lin, G.L., McGinley, J.P., Drysdale, S.B., and Pollard, A.J. (2018). Epidemiology and Immune Pathogenesis of Viral Sepsis. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02147"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R202","DOI":"10.1186\/cc12896","article-title":"Characteristics and outcomes of culture-negative versus culture-positive severe sepsis","volume":"17","author":"Phua","year":"2013","journal-title":"Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1164\/rccm.201310-1875OC","article-title":"Association between source of infection and hospital mortality in patients who have septic shock","volume":"189","author":"Leligdowicz","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4161\/viru.27372","article-title":"Epidemiology of severe sepsis","volume":"5","author":"Mayr","year":"2014","journal-title":"Virulence"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1097\/SHK.0000000000000731","article-title":"Patterns in Bacterial- and Viral-Induced Immunosuppression and Secondary Infections in the ICU","volume":"47","author":"Koch","year":"2017","journal-title":"Shock"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","volume":"20","author":"Dong","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s004410100365","article-title":"Semaphorin-neuropilin-1 interactions in plasticity and regeneration of adult neurons","volume":"305","author":"Gavazzi","year":"2001","journal-title":"Cell Tissue Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.drudis.2012.11.013","article-title":"Targeting VEGF signalling via the neuropilin co-receptor","volume":"18","author":"Djordjevic","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1038\/nsmb.2416","article-title":"Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex","volume":"19","author":"Janssen","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1189\/jlb.0208090","article-title":"Neuropilin-1 is a receptor for transforming growth factor beta-1, activates its latent form, and promotes regulatory T cell activity","volume":"84","author":"Glinka","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-1-4615-0119-0_4","article-title":"Neuropilin-1 in the immune system","volume":"515","author":"Romeo","year":"2002","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/ni789","article-title":"A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response","volume":"3","author":"Tordjman","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.immuni.2008.01.012","article-title":"Neuropilin-1 expression on regulatory T cells enhances their interactions with dendritic cells during antigen recognition","volume":"28","author":"Sarris","year":"2008","journal-title":"Immunity"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00262-013-1500-0","article-title":"Neuropilin 1: Function and therapeutic potential in cancer","volume":"63","author":"Chaudhary","year":"2014","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.4161\/mabs.1.4.8885","article-title":"Identification of circulating neuropilin-1 and dose-dependent elevation following anti-neuropilin-1 antibody administration","volume":"1","author":"Lu","year":"2009","journal-title":"MAbs"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.advms.2025.02.007","article-title":"High levels of soluble neuropilin-1 in critically ill multiple trauma\/surgical patients","volume":"70","author":"Vrettou","year":"2025","journal-title":"Adv. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.clinimag.2020.09.004","article-title":"Computed tomography for detection of septic foci: Retrospective analysis of patients presenting to the emergency department","volume":"69","author":"Pohlan","year":"2021","journal-title":"Clin. Imaging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6466","DOI":"10.1007\/s00330-024-10701-y","article-title":"Computed tomography in patients with sepsis presenting to the emergency department: Exploring its role in light of patient outcomes","volume":"34","author":"Pohlan","year":"2024","journal-title":"Eur. Radiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"c179","DOI":"10.1159\/000339789","article-title":"KDIGO clinical practice guidelines for acute kidney injury","volume":"120","author":"Khwaja","year":"2012","journal-title":"Nephron Clin. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014a metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J. Biomed. Inform."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Harris, P.A., Taylor, R., Minor, B.L., Elliott, V., Fernandez, M., O\u2019Neal, L., McLeod, L., Delacqua, G., Delacqua, F., and Kirby, J. (2019). The REDCap consortium: Building an international community of software platform partners. J. Biomed. Inform., 95.","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sultan, R.H., Elesawy, B.H., Ali, T.M., Abdallah, M., Assal, H.H., Ahmed, A.E., and Ahmetd, O.M. (2022). Correlations between Kidney and Heart Function Bioindicators and the Expressions of Toll-Like, ACE2, and NRP-1 Receptors in COVID-19. Vaccines, 10.","DOI":"10.1101\/2022.04.08.22273322"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41392-021-00687-0","article-title":"Pattern recognition receptors in health and diseases","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.smim.2003.10.003","article-title":"TLR signaling pathways","volume":"16","author":"Takeda","year":"2004","journal-title":"Semin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gao, Y.L., Wang, C.X., Wang, Z.Y., Li, W.J., Liu, Y.C., Shou, S.T., and Chai, Y.F. (2021). Targeting Neuropilin-1 Suppresses the Stability of CD4+ CD25+ Regulatory T Cells via the NF-\u03baB Signaling Pathway in Sepsis. Infect. Immun., 89.","DOI":"10.1128\/IAI.00399-20"},{"key":"ref_28","first-page":"56","article-title":"Sepsis-induced immunosuppression: Mechanisms, diagnosis and current treatment options","volume":"9","author":"Liu","year":"2022","journal-title":"Mil. Med. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s15010-022-01803-0","article-title":"Immunologic response in bacterial sepsis is different from that in COVID-19 sepsis","volume":"50","author":"Perschinka","year":"2022","journal-title":"Infection"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Song, J., Park, D.W., Moon, S., Cho, H.-J., Park, J.H., Seok, H., and Choi, W.S. (2019). Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: A prospective controlled study according to the Sepsis-3 definitions. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4618-7"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1073\/pnas.040337597","article-title":"Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity","volume":"97","author":"Gagnon","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4590","DOI":"10.1172\/JCI75371","article-title":"Protein kinase LKB1 promotes RAB7-mediated neuropilin-1 degradation to inhibit angiogenesis","volume":"124","author":"Okon","year":"2014","journal-title":"J. Clin. Investig."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/997\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:10:48Z","timestamp":1760033448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,16]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["v17070997"],"URL":"https:\/\/doi.org\/10.3390\/v17070997","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2025,7,16]]}}}