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. 2022 Sep:242:109091.
doi: 10.1016/j.clim.2022.109091. Epub 2022 Aug 6.

Soluble urokinase Plasminogen Activator Receptor (suPAR) levels are predictive of COVID-19 severity: an Italian experience

Maria Infantino  1 , Lorenza Morena  2 , Massimo Antonio Di Pietro  3 , Benedetta Romanin  3 , Barbara Cimolato  3 , Beatrice Anna Luisa Rocca  3 , Silvia Tunnera  3 , Giulia Modi  3 , Marta Tilli  3 , Valentina Grossi  4 , Barbara Lari  4 , Helena Cerutti  5 , Giulia Tesi  5 , Valentina Anrò  5 , Alessandra Cartocci  6 , Maurizio Benucci  7 , Francesca Veneziani  2 , Patrizia Casprini  2 , Mariangela Manfredi  4
Affiliations

Soluble urokinase Plasminogen Activator Receptor (suPAR) levels are predictive of COVID-19 severity: an Italian experience

Maria Infantino et al. Clin Immunol. 2022 Sep.

Abstract

Background: The soluble urokinase Plasminogen Activator Receptor (suPAR) has been identified as a reliable marker of COVID-19 severity, helping in personalizing COVID-19 therapy. This study aims to evaluate the correlation between suPAR levels and COVID-19 severity, in relation to the traditional inflammatory markers.

Methods: Sera from 71 COVID-19 patients were tested for suPAR levels using Chorus suPAR assay (Diesse Diagnostica Senese SpA, Italy). suPAR levels were compared with other inflammatory markers: IL-1β, IL-6, TNF-α, circulating calprotectin, neutrophil and lymphocyte counts, and Neutrophil/Lymphocytes Ratio (NLR). Respiratory failure, expressed as P/F ratio, and mortality rate were used as indicators of disease severity.

Results: A positive correlation of suPAR levels with IL-6 (r = 0.479, p = 0.000), TNF-α (r = 0.348, p = 0.003), circulating calprotectin (r = 0.369, p = 0.002), neutrophil counts (r = 0.447, p = 0.001), NLR (r = 0.492, p = 0.001) has been shown. Stratifying COVID-19 population by suPAR concentration above and below 6 ng/mL, we observed higher levels of circulating calprotectin (10.1 μg/mL, SD 7.9 versus 6.4 μg/mL, SD 7.5, p < 0.001), higher levels of P/F ratio (207.5 IQR 188.3 vs 312.0 IQR 127.8, p = 0.013) and higher mortality rate. Median levels of suPAR were increased in all COVID-19 patients requiring additional respiratory support (Nasal Cannula, Venturi Mask, BPAP and CPAP) (6.5 IQR = 4.9) compared to the group at room air (4.6 IQR = 4.2).

Conclusion: suPAR levels correlate with disease severity and survival rate of COVID-19 patients, representing a promising prognostic biomarker for the risk assessment of the disease.

Keywords: COVID-19; Inflammatory markers; Respiratory support; Risk assessment; suPAR.

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Conflict of interest statement

Declaration of Competing Interest Helena Cerutti, Giulia Tesi, Valentina Anrò are employees of Diesse Diagnostica Senese SpA (Siena, Italy). The other authors have no conflict of interests.

Figures

Fig. 1
Fig. 1
suPAR levels compared to clinical laboratory parameters. Spearman's correlation coefficients were statistically significant with p < 0.05. IL-1β, interleukin 1β; IL-6, interleukin 6; TNF-α, tumor necrosis factor alpha; CRP, C-Reactive Protein; s-calprotectin, serum-calprotectin; NLR, Neutrophils/Lymphocytes ratio.
Fig. 2
Fig. 2
Comparison of s-calprotectin between groups with suPAR levels above and below the cutoff value of 6 ng/mL (Mann Whitney U test; p < 0.05).
Fig. 3
Fig. 3
Respiratory failure expressed as P/F ratio and suPAR levels of COVID-19 patients at admission.
Fig. 4
Fig. 4
Kaplan-Meier survival analysis: comparison between groups with suPAR levels above and below the cutoff value of 6 ng/mL in predicting mortality.
See this image and copyright information in PMC

References

    1. Gubernatorova E.O., Gorshkova E.A., Polinova A.I., Drutskaya M.S. IL-6: relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020;53:13–24. - PMC - PubMed
    1. Dujardin R.W.G., Hilderink B.N., Haksteen W.E., Middeldorp S., Vlaar A.P.J., Thachil J., et al. Biomarkers for the prediction of venous thromboembolism in critically ill COVID-19 patients. Thromb. Res. 2020;196:308–312. - PMC - PubMed
    1. Fei F., Smith J.A., Cao L. Clinical laboratory characteristics in patients with suspected COVID-19: one single-institution experience. J. Med. Virol. 2021;93:1665–1671. - PMC - PubMed
    1. Mahler M., Meroni P.L., Infantino M., Buhler K.A., Fritzler M.J. Circulating calprotectin as a biomarker of COVID-19 severity. Expert. Rev. Clin. Immunol. 2021;17:431–443. - PMC - PubMed
    1. Plesner T., Behrendt N., Ploug M. Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, Upar. Stem Cells. 1997;15:398–408. - PubMed