Background/Objectives: This retrospective study analyzed soluble urokinase plasminogen activator receptor (suPAR) plasma levels alongside routine inflammatory markers, including the neutrophil-to-lymphocyte count ratio, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and D-dimers in COVID-19 patients hospitalized during the Omicron wave of the pandemic. Methods: We measured plasma suPAR levels using a suPARnostic® Quick Triage kit. We divided COVID-19 patients into two groups based on the severity of SARS-CoV-2 infection according to the National Institutes of Health (NIH) criteria. The logistic regression analysis tested the predictive value of the biomarkers. Results: We evaluated 160 consecutive COVID-19 patients hospitalized between January and August 2022. The cohort exhibited a high incidence of comorbidities, with an in-hospital mortality rate of 5.6%. Upon admission, the median suPAR plasma levels were not significantly different between patients with mild COVID-19 (n = 110) and those with moderate/severe disease (n = 50), with 7.25 ng/mL and 7.55 ng/mL, respectively. We observed significant differences (p < 0.01) between the groups for CRP and IL-6 levels that were higher in moderate/severe disease than in mild infection. Additionally, suPAR plasma levels were above the normal range (0-2.00 ng/mL) in all patients, with a significant positive correlation identified between suPAR levels and serum IL-6, PCT, and creatinine levels. Conclusions: These findings indicate that COVID-19 during the Omicron wave is strongly associated with elevated suPAR levels; however, these levels do not directly correlate with the severity of SARS-CoV-2 infection.

Department of Infectious Diseases Military University Hospital Prague and 1st Faculty of Medicine of Charles University 16902 Prague Czech Republic

Military Health Institute Military Medical Agency 16200 Prague Czech Republic

Ústřední Vojenská Nemocnice Vojenská Fakultní Nemonice Praha U Vojenské Nemocnice 1200 Praha 6 Břevnov 16902 Prague Czech Republic

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Elshazli R.M., Toraih E.A., Elgaml A., El-Mowafy M., El-Mesery M., Amin M.N., Hussein M.H., Killackey M.T., Fawzy M.S., Kandil E. Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients. PLoS ONE. 2020;15:e0238160. doi: 10.1371/journal.pone.0238160. PubMed DOI PMC

Metlay J.P., Waterer G.W. Treatment of community-acquired pneumonia during the coronavirus disease 2019 (COVID-19) Pandemic. Ann. Intern. Med. 2020;173:304–305. doi: 10.7326/M20-2189. PubMed DOI PMC

Shah S., Shah K., Patel S.B., Patel F.S., Osman M., Velagapudi P., Turagam M.K., Lakkireddy D., Garg J. Elevated D-dimer levels are associated with increased risk of mortality in coronavirus disease 2019: A systematic review and meta-analysis. Cardiol. Rev. 2020;28:295–302. doi: 10.1097/CRD.0000000000000330. PubMed DOI PMC

Backes Y., van der Sluijs K.F., Mackie D.P., Tacke F., Koch A., Tenhunen J.J., Schultz M.J. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: A systematic review. Intensive Care Med. 2012;38:1418–1428. doi: 10.1007/s00134-012-2613-1. PubMed DOI PMC

Lipinski M., Rydzewska-Rosolowska A., Rydzewski A., Cicha M., Rydzewska G. Soluble urokinase-type plasminogen activator receptor (suPAR) in patients with acute pancreatitis (AP)—Progress in prediction of AP severity. Pancreatology. 2017;17:24–29. doi: 10.1016/j.pan.2016.11.005. PubMed DOI

Rovina N., Akinosoglou K., Eugen-Olsen J., Hayek S., Reiser J., Giamarellos-Bourboulis E.J. Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Crit. Care. 2020;24:187. doi: 10.1186/s13054-020-02897-4. PubMed DOI PMC

Altintas I., Eugen-Olsen J., Seppälä S., Tingleff J., Stauning M.A., El Caidi N.O., Elmajdoubi S., Gamst-Jensen H., Lindstrøm M.B., Rasmussen L.J.H., et al. suPAR cut-offs for risk stratification in patients with symptoms of COVID-19. Biomark. Insights. 2021;15:11772719211034685. doi: 10.1177/11772719211034685. PubMed DOI PMC

Napolitano F., Di Spigna G., Vargas M., Iacovazzo C., Pinchera B., Spalletti Cernia D., Ricciardone M., Covelli B., Servillo G., Gentile I., et al. Soluble urokinase receptor as a promising marker for early prediction of outcome in COVID-19 hospitalized patients. J. Clin. Med. 2021;10:4914. doi: 10.3390/jcm10214914. PubMed DOI PMC

Kyriazopoulou E., Panagopoulos P., Metallidis S., Dalekos G.N., Poulakou G., Gatselis N., Karakike E., Saridaki M., Loli G., Stefos A., et al. An open label trial of anakinra to prevent respiratory failure in COVID-19. eLife. 2021;10:66125. doi: 10.7554/eLife.66125. PubMed DOI PMC

D’Alonzo D., De Fenza M., Pavone V. COVID-19 and pneumonia: A role for the uPA/uPAR system. Drug Discov. Today. 2020;25:1528–1534. doi: 10.1016/j.drudis.2020.06.013. PubMed DOI PMC

Nusshag C., Rupp C., Schmitt F., Krautkraemer E., Speer C., Kaelble F., Tamulyte S., Bruckner T., Zeier M., Reiser J., et al. Cell cycle biomarkers and soluble urokinase-type plasminogen activator receptor for the prediction of sepsis-induced acute kidney injury requiring renal replacement therapy: A prospective, exploratory study. Crit. Care Med. 2019;47:999–1007. doi: 10.1097/CCM.0000000000004042. PubMed DOI PMC

Sudhini Y.R., Wei C., Reiser J. suPAR: An inflammatory mediator for kidneys. Kidney Dis. 2022;8:265–274. doi: 10.1159/000524965. PubMed DOI PMC

Loonen A.J.M., Kesarsing C., Kusters R., Hilbink M., Wever P.C., van den Brule A.J.C. High pneumococcal DNA load, procalcitonin and suPAR levels correlate to severe disease development in patients with pneumococcal pneumonia. Eur. J. Clin. Microbiol. Infect. Dis. 2017;36:1541–1547. doi: 10.1007/s10096-017-2963-2. PubMed DOI

Geboers D.G., de Beer F.M., Boer A.M.T.D., van der Poll T., Horn J., Cremer O.L., Bonten M.J., Ong D.S., Schultz M.J., Bos L.D. Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients. Intensive Care Med. 2015;41:1281–1290. doi: 10.1007/s00134-015-3924-9. PubMed DOI

Vassiliou A.G., Zacharis A., Vrettou C.S., Keskinidou C., Jahaj E., Mastora Z., Orfanos S.E., Dimopoulou I., Kotanidou A. Comparison of the mortality prediction value of soluble urokinase plasminogen activator receptor (suPAR) in COVID-19 and sepsis. Diagnostics. 2022;12:1261. doi: 10.3390/diagnostics12051261. PubMed DOI PMC

Huang M., Li L., Shen J., Wang Y., Wang R., Yuan C., Huang M., Jiang L. Plasma levels of the active form of suPAR are associated with COVID-19 severity. Crit. Care. 2020;24:704. doi: 10.1186/s13054-020-03336-0. PubMed DOI PMC

Wlazel R.N., Szwabe K., Guligowska A., Kostka T. Soluble urokinase plasminogen activator receptor level in individuals of advanced age. Sci. Rep. 2020;10:15462. doi: 10.1038/s41598-020-72377-w. PubMed DOI PMC

Langkilde A., Jakobsen T.L., Bandholm T.Q., Eugen-Olsen J., Blauenfeldt T., Petersen J., Andersen O. Inflammation and post-operative recovery in patients undergoing total knee arthroplasty-secondary analysis of a randomized controlled trial. Osteoarthr. Cartil. 2017;25:1265–1273. doi: 10.1016/j.joca.2017.03.008. PubMed DOI

Qin C., Zhou L., Hu Z., Zhang S., Yang S., Tao Y., Xie C., Ma K., Shang K., Wang W., et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin. Infect. Dis. 2020;71:762–768. doi: 10.1093/cid/ciaa248. PubMed DOI PMC

Villard O., Morquin D., Molinari N., Raingeard I., Nagot N., Cristol J.P., Jung B., Roubille C., Foulongne V., Fesler P., et al. The plasmatic aldosterone and C-reactive protein levels, and the severity of COVID-19: The Dyhor-19 study. J. Clin. Med. 2020;9:2315. doi: 10.3390/jcm9072315. PubMed DOI PMC

Luan Y.Y., Yin C.H., Yao Y.M. Update advances on C-reactive protein in COVID-19 and other viral infections. Front. Immunol. 2021;12:720363. doi: 10.3389/fimmu.2021.720363. PubMed DOI PMC

Bivona G., Agnello L., Ciaccio M. Biomarkers for prognosis and treatment response in COVID-19 patients. Ann. Lab. Med. 2021;41:540–548. doi: 10.3343/alm.2021.41.6.540. PubMed DOI PMC

Chalupa P., Beran O., Herwald H., Kaspříková N., Holub M. Evaluation of potential biomarkers for the discrimination of bacterial and viral infections. Infection. 2011;39:411–417. doi: 10.1007/s15010-011-0126-4. PubMed DOI

Gonzalez L., Holman T., Wait D., Abenojar P. Experience with procalcitonin use during the COVID-19 pandemic. Eur. J. Intern. Med. 2022;102:116–117. doi: 10.1016/j.ejim.2022.04.002. PubMed DOI PMC

Battaglini D., Lopes-Pacheco M., Castro-Faria-Neto H.C., Pelosi P., Rocco P.R. Laboratory biomarkers for diagnosis and prognosis in COVID-19. Front. Immunol. 2022;13:857573. doi: 10.3389/fimmu.2022.857573. PubMed DOI PMC

Tabassum T., Rahman A., Araf Y., Ullah M.A., Hosen M.J. Prospective selected biomarkers in COVID-19 diagnosis and treatment. Biomark. Med. 2020;15:1435–1449. doi: 10.2217/bmm-2021-0038. PubMed DOI PMC

Callaway E. What Omicron’s BA.4 and BA.5 variants mean for the pandemic. Nature. 2022;606:848–849. doi: 10.1038/d41586-022-01730-y. PubMed DOI