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Serum Sphingosine-1-Phosphate as Novel Prognostic and Predictive Biomarker for COVID-19 Severity and Morbidity and Its Implications in Clinical Management

29 Pages Posted: 30 Aug 2020

See all articles by Giovanni Marfia

Giovanni Marfia

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Laboratory of Experimental Neurosurgery and Cell Therapy

Stefania Navone

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

Laura Guarnaccia

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

Rolando Campanella

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

Michele Mondoni

Università degli Studi di Milano - Respiratory Unit

Marco Locatelli

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

Alessandra Barassi

Laboratory of Clinical Biochemistry, ASST Santi Paolo e Carlo,Department of Health Sciences, Università degli Studi di Milano

Laura Fontana

Department of Medical-Surgical Physiopathology and Transplantation, Università degli Studi di Milano

Fabrizio Palumbo

Istituto di Medicina Aerospaziale "A. Mosso", Aeronautica Militare, viale dell’Aviazione

Emanuele Garzia

Department of Medical-Surgical Physiopathology and Transplantation, Università degli Studi di Milano

Giuseppe Ciniglio Appiani

Istituto di Medicina Aerospaziale "A. Mosso", Aeronautica Militare

Davide Chiumello

SC Anestesia e Rianimazione, ASST Santi Paolo e Carlo

Monica Miozzo

Reproductive Medicine Unit, ASST Santi Paolo e Carlo, Università degli Studi di Milano

Stefano Centanni

Respiratory Unit, ASST Santi Paolo e Carlo, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano

Laura Riboni

Università degli Studi di Milano

More...

Abstract

Background:  Since December 2019, COVID-19 has widely spread throughout the world, causing thousands of deaths. Clinical characteristics of COVID-19 patients have been widely reported, but significative disease-associated biomarkers are needed. We aimed to evaluate the prognostic power of circulating sphingosine-1-phosphate (S1P) in COVID-19, to propose S1P as a novel prognostic and predictive biomarker.

Methods: Clinical and blood parameters were investigated in 111 COVID-19 patients (COV) and 47 healthy subject (HLT), with a particular focus on patients who required intensive care unit (ICU) admission. We measured serum levels of S1P and its main transporter apolipoprotein M (apoM) by ELISA assay. Correlation with clinical and blood parameters were performed by Pearson correlations. Univariable and multivariable regression analysis were performed to assess the interaction between clinically significant factors and ICU admission. Further, Cox regression was used to evaluate the prognostic power of S1P for ICU admission and mortality.

Findings:  We reported statistically significant alterations of several blood parameters in COV, as an increase of white blood cells, neutrophil-to-lymphocyte ratio, ferritin, D-dimer and fibrinogen, and a decrease in hemoglobin, lymphocyte count and total proteins. Our major finding is the drop of serum S1P level in COV, strongly associated with the decrease of red blood cells, the major source of plasmatic S1P, and both apoM and albumin, the most important transporters of circulating S1P. The multivariable regression analysis revealed that S1P is the most important predictor for ICU admission (OR:39·45, [95%CI:1·51-1031·60]; p=0·027), and Cox proportional-hazards model  demonstrated a high power of S1P in predicting patient’s outcome.

Interpretation: COVID-19 patients showed a drastic decrease of serum S1P, suggesting that circulating S1P levels may be clinically used as negative biomarkers to predict severity/mortality of COVID-19. Taken together, our results suggest that restoring S1P at physiological level may represent a novel therapeutic strategy.

Funding:  Italian Ministry of Health.

Declaration of Interests: All authors declare no competing interests.

Ethics Approval Statement:This prospective, case-control study was approved by the Ethic Committee of Ospedale San Paolo in Milan, Lombardy, Italy (COST Action n.2020/ST/057).

Keywords: COVID-19, Coronavirus, SARS-CoV-2, sphingosine-1-phosphate, biomarkers, Intensive Care Unit, apolipoprotein M, clinical management

Suggested Citation

Marfia, Giovanni and Navone, Stefania and Guarnaccia, Laura and Campanella, Rolando and Mondoni, Michele and Locatelli, Marco and Barassi, Alessandra and Fontana, Laura and Palumbo, Fabrizio and Garzia, Emanuele and Ciniglio Appiani, Giuseppe and Chiumello, Davide and Miozzo, Monica and Centanni, Stefano and Riboni, Laura, Serum Sphingosine-1-Phosphate as Novel Prognostic and Predictive Biomarker for COVID-19 Severity and Morbidity and Its Implications in Clinical Management. Available at SSRN: https://ssrn.com/abstract=3668364 or http://dx.doi.org/10.2139/ssrn.3668364

Giovanni Marfia (Contact Author)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Laboratory of Experimental Neurosurgery and Cell Therapy ( email )

Milan
Italy

Stefania Navone

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ( email )

Laura Guarnaccia

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ( email )

Rolando Campanella

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ( email )

Michele Mondoni

Università degli Studi di Milano - Respiratory Unit ( email )

Milan
Italy

Marco Locatelli

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico ( email )

Alessandra Barassi

Laboratory of Clinical Biochemistry, ASST Santi Paolo e Carlo,Department of Health Sciences, Università degli Studi di Milano ( email )

Laura Fontana

Department of Medical-Surgical Physiopathology and Transplantation, Università degli Studi di Milano ( email )

Fabrizio Palumbo

Istituto di Medicina Aerospaziale "A. Mosso", Aeronautica Militare, viale dell’Aviazione ( email )

Emanuele Garzia

Department of Medical-Surgical Physiopathology and Transplantation, Università degli Studi di Milano ( email )

Giuseppe Ciniglio Appiani

Istituto di Medicina Aerospaziale "A. Mosso", Aeronautica Militare ( email )

Davide Chiumello

SC Anestesia e Rianimazione, ASST Santi Paolo e Carlo ( email )

Monica Miozzo

Reproductive Medicine Unit, ASST Santi Paolo e Carlo, Università degli Studi di Milano ( email )

Stefano Centanni

Respiratory Unit, ASST Santi Paolo e Carlo, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano

Laura Riboni

Università degli Studi di Milano

via Festa del Perdono, 7
Milano
Italy

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