{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:07:51Z","timestamp":1760144871310,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Background: Pneumonia is one of the most common infectious diseases, mostly caused by viruses or bacteria. In response to bacteria or viruses which are different but which also are partly overlapping, innate and adaptive immune responses are induced, which can be quantified using the determination of specific biomarkers. Among these, C-reactive protein (CRP) has been established as a marker of innate immune function, whereas Neopterin, which is mainly produced upon stimulation with interferon-gamma, reflects cellular immune activation. Aim: We investigated inflammation markers in patients with microbiologically confirmed viral or bacterial pneumonia, and studied the potential of CRP, Neopterin, and the CRP\/Neopterin ratio to distinguish between viral and bacterial pathogenesis. Furthermore, we examined, how often neuropsychiatric symptoms occur in patients suffering from different kinds of pneumonia. Patients and method: A total of 194 patients diagnosed with either coronavirus disease 2019 (COVID-19) (n = 63), bacterial pneumonia (n = 58), Influenza infection (n = 10), Influenza and a bacterial superinfection (n = 9), and COVID-19 patients with a bacterial superinfection (n = 54) were included in our pilot study. Clinical as well as laboratory parameters were determined shortly after admission. Results: We found significantly higher CRP\/Neopterin ratios in patients with bacterial pneumonia (median: 0.34) and lower CRP\/Neopterin ratios in patients hospitalized with COVID-19 infection (median: 0.03; p &lt; 0.001). Both in men and in women, the CRP\/Neopterin ratio was able to distinguish between viral and bacterial pathogens, but also was able to detect bacterial super-infection (BSI) in subjects with initial viral pneumonia (p &lt; 0.001). Patients with BSI presented with significantly lower CRP\/Neopterin ratios (median 0.08) than patients with bacterial infection only (median 0.34; p &lt; 0.001). Interestingly, COVID-19 patients had a decreased physical functioning (as reflected in the ECOG score) and a higher frequency of fatigue (84.1%) and neurological symptoms (54.8%) than patients with pneumonia, due to other underlying pathogens. Patients that reported fatigue during viral and bacterial pneumonia presented with lower CRP concentrations than patients without it. Conclusions: The CRP\/Neopterin ratio is useful to differentiate between viral and bacterial pathogenesis. The occurrence of neuropsychiatric symptoms in pneumonia appears to depend on the kind of pathogen causing the infection. Lower CRP concentrations at admission appear to be related to fatigue during acute viral and bacterial infection.<\/jats:p>","DOI":"10.3390\/microorganisms12061099","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T03:38:30Z","timestamp":1716953910000},"page":"1099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CRP\/Neopterin Ratio and Neuropsychiatric Symptoms in Patients with Different Forms of Pneumonia: Results of a Pilot Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Katharina Konstanze Lilly","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Corda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Steinmayr","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Burkert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1627-9563","authenticated-orcid":false,"given":"Dietmar","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Institute of Biological Chemistry, Biocenter, CCB, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1532-5177","authenticated-orcid":false,"given":"Johanna","family":"Gostner","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry, Biocenter, CCB, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Hofer","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry, Biocenter, CCB, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Parrakova","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry, Biocenter, CCB, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Gasslitter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-2158","authenticated-orcid":false,"given":"G\u00fcnter","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4901-8861","authenticated-orcid":false,"given":"Christian","family":"Irsara","sequence":"additional","affiliation":[{"name":"Central Institute for Medical and Chemical Laboratory Diagnostics, University Hospital of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Maier","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics and Informatics, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Griesmacher","sequence":"additional","affiliation":[{"name":"Central Institute for Medical and Chemical Laboratory Diagnostics, University Hospital of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-111X","authenticated-orcid":false,"given":"Rosa","family":"Bellmann-Weiler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Kurz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Innsbruck Medical University, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1080\/14760584.2023.2261785","article-title":"Clinical, economic, and humanistic burden of community acquired pneumonia in Europe: A systematic literature review","volume":"22","author":"Tsoumani","year":"2023","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1161\/01.CIR.0000096055.62724.C5","article-title":"Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells","volume":"108","author":"Willerson","year":"2003","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3389\/fpsyt.2015.00097","article-title":"Disturbed Amino Acid Metabolism in HIV: Association with Neuropsychiatric Symptoms","volume":"6","author":"Gostner","year":"2015","journal-title":"Front. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"287","DOI":"10.4103\/ijmr.IJMR_1678_19","article-title":"Community-acquired bacterial pneumonia in adults: An update","volume":"151","author":"Eshwara","year":"2020","journal-title":"Indian J. Med. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.trim.2011.06.005","article-title":"Influence of immunosuppressive agents on tryptophan degradation and neopterin production in human peripheral blood mononuclear cells","volume":"25","author":"Schroecksnadel","year":"2011","journal-title":"Transpl. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Piater, T., Gietl, M., Hofer, S., Gostner, J.M., Sahanic, S., Tancevski, I., Sonnweber, T., Pizzini, A., Egger, A., and Schennach, H. (2023). Persistent Symptoms and IFN-\u03b3-Mediated Pathways after COVID-19. J. Pers. Med., 13.","DOI":"10.3390\/jpm13071055"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1080\/15412555.2016.1266317","article-title":"Diagnostic and Prognostic Value of Inflammatory Parameters Including Neopterin in the Setting of Pneumonia, COPD, and Acute Exacerbations, COPD","volume":"14","author":"Pizzini","year":"2017","journal-title":"J. Chronic Obstr. Pulm. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lafond, K.E., Porter, R.M., Whaley, M.J., Suizan, Z., Ran, Z., Aleem, M.A., Thapa, B., Sar, B., Proschle, V.S., and Peng, Z. (2021). Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis. PLoS Med., 18.","DOI":"10.1371\/journal.pmed.1003550"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1041.e1","DOI":"10.1016\/j.cmi.2021.03.012","article-title":"Persistent COVID-19 symptoms are highly prevalent 6 months after hospitalization: Results from a large prospective cohort","volume":"27","author":"Ghosn","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S2666-5247(21)00090-2","article-title":"Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: A multicentre, prospective cohort study","volume":"2","author":"Russell","year":"2021","journal-title":"Lancet Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.amjmed.2007.10.040","article-title":"Complications of viral influenza","volume":"121","author":"Rothberg","year":"2008","journal-title":"Am. J. Med."},{"key":"ref_12","first-page":"67","article-title":"Influenza-related pneumonia","volume":"12","author":"Almond","year":"2012","journal-title":"Clin. Med. Lond. Engl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1937013","DOI":"10.1080\/21688370.2021.1937013","article-title":"The blood-gas barrier in COVID-19: An overview of the effects of SARS-CoV-2 infection on the alveolar epithelial and endothelial cells of the lung","volume":"9","author":"Shirvaliloo","year":"2021","journal-title":"Tissue Barriers"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Brown, B., Ojha, V., Fricke, I., Al-Sheboul, S.A., Imarogbe, C., Gravier, T., Green, M., Peterson, L., Koutsaroff, I.P., and Demir, A. (2023). Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms. Vaccines, 11.","DOI":"10.3390\/vaccines11020408"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.intimp.2013.06.034","article-title":"Neutrophil cell surface receptors and their intracellular signal transduction pathways","volume":"17","author":"Futosi","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ahmed, N., Khan, M., Saleem, W., Karobari, M.I., Mohamed, R.N., Heboyan, A., Rabaan, A.A., Mutair, A.A., Alhumaid, S., and Alsadiq, S.A. (2022). Evaluation of Bi-Lateral Co-Infections and Antibiotic Resistance Rates among COVID-19 Patients. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020276"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.3389\/fimmu.2018.01366","article-title":"Streptococcus pneumoniae\u2019s Virulence and Host Immunity: Aging, Diagnostics, and Prevention","volume":"9","author":"Brooks","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"41","DOI":"10.4137\/IJTR.S26862","article-title":"Tryptophan Catabolism in Chronic Viral Infections: Handling Uninvited Guests","volume":"8","author":"Mehraj","year":"2015","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/irv.12677","article-title":"Assessment of neopterin and indoleamine 2,3-dioxygenase activity in patients with seasonal influenza: A pilot study","volume":"13","author":"Pizzini","year":"2019","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jad.2007.09.005","article-title":"IFN-gamma mediated pathways in patients with fatigue and chronic active Epstein Barr virus-infection","volume":"108","author":"Kurz","year":"2008","journal-title":"J. Affect. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1515\/cclm-2016-0912","article-title":"Activation of the tryptophan\/serotonin pathway is associated with severity and predicts outcomes in pneumonia: Results of a long-term cohort study","volume":"55","author":"Meier","year":"2017","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11786469231154244","DOI":"10.1177\/11786469231154244","article-title":"Interferon-gamma Mediated Metabolic Pathways in Hospitalized Patients During Acute and Reconvalescent COVID-19","volume":"16","author":"Gietl","year":"2023","journal-title":"Int. J. Tryptophan Res. IJTR"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11786469231220781","DOI":"10.1177\/11786469231220781","article-title":"Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study","volume":"16","author":"Taenzer","year":"2023","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fimmu.2020.00249","article-title":"Inflammation-Induced Tryptophan Breakdown is Related with Anemia, Fatigue, and Depression in Cancer","volume":"11","author":"Lanser","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jinf.2008.11.007","article-title":"Diagnostic utility of CRP to neopterin ratio in patients with acute respiratory tract infections","volume":"58","author":"Rainer","year":"2009","journal-title":"J. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"579220","DOI":"10.3389\/fimmu.2020.579220","article-title":"Immunosenescence and Inflammaging: Risk Factors of Severe COVID-19 in Older People","volume":"11","author":"Pietrobon","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_27","first-page":"496","article-title":"Does gender influence clinical expression and disease outcomes in COVID-19? A systematic review and meta-analysis","volume":"99","author":"Ortolan","year":"2020","journal-title":"Int. J. Tryptophan Res. IJTR"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103268","DOI":"10.1016\/j.msard.2021.103268","article-title":"Long COVID or post COVID-19 syndrome","volume":"55","author":"Levy","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104779","DOI":"10.1016\/j.idnow.2023.104779","article-title":"Long-term complications after infection with SARS-CoV-1, influenza and MERS-CoV\u2014Lessons to learn in long COVID?","volume":"53","author":"Hansen","year":"2023","journal-title":"Infect. Dis. Now"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1016\/j.cell.2022.06.008","article-title":"Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation","volume":"185","author":"Lu","year":"2022","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bbi.2021.07.018","article-title":"Psychiatric and neuropsychiatric sequelae of COVID-19\u2014A systematic review","volume":"97","author":"Schou","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S2215-0366(20)30203-0","article-title":"Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: A systematic review and meta-analysis with comparison to the COVID-19 pandemic","volume":"7","author":"Rogers","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.amjmed.2012.12.006","article-title":"Functional disability, cognitive impairment, and depression after hospitalization for pneumonia","volume":"126","author":"Davydow","year":"2013","journal-title":"Am. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.bbi.2015.12.005","article-title":"The risk of new onset depression in association with influenza\u2014A population-based observational study","volume":"53","author":"Bornand","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00705-023-05801-x","article-title":"SARS-CoV-2 and the nervous system: Current perspectives","volume":"168","author":"Pattanaik","year":"2023","journal-title":"Arch. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.1007\/s00415-023-11912-x","article-title":"Central nervous system complications in SARS-CoV-2-infected patients","volume":"270","author":"Li","year":"2023","journal-title":"J. Neurol."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/6\/1099\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:49:58Z","timestamp":1760107798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/6\/1099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,29]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["microorganisms12061099"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12061099","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2024,5,29]]}}}