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Kinetics of Biomarkers Associated with Organ Dysfunction and Inflammatory Status and Their Association with Disease Outcomes in Severe COVID-19: A Longitudinal Cohort Study

46 Pages Posted: 7 Aug 2020

See all articles by Abderrahim Oussalah

Abderrahim Oussalah

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics; University of Lorraine - INSERM UMR_S 1256

Stanislas Gleye

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Isabelle Clerc Urmes

University of Lorraine - University Hospital of Nancy - Department of Methodology

Elodie Laugel

University of Lorraine - Nancy-Université

Françoise Barbé

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Sophie Orlowski

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Catherine Malaplate

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Isabelle Aimone-Gastin

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Beatrice Maatem Caillierez

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Marc Merten

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Elise Jeannesson

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Raphaël Kormann

University of Lorraine - University Hospital of Nancy - Department of Nephrology

Jean-Luc Olivier

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Rosa-Maria Rodriguez-Guéant

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Farès Namour

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Sybille Bevilacqua

University of Lorraine - University Hospital of Nancy - Department of Infectious Diseases

Nathalie Thilly

University of Lorraine - University Hospital of Nancy - Department of Methodology, Promotion and Investigation

Marie-Reine Losser

University of Lorraine - University Hospital of Nancy - Department of Anesthesiology and Intensive Care Medicine

Antoine Kimmoun

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

Luc Frimat

University of Lorraine - University Hospital of Nancy - Department of Nephrology

Bruno Levy

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

Sébastien Gibot

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

Evelyne Schvoerer

University of Lorraine - Department of Virology

Jean-Louis Gueant

University of Lorraine - Nutrition, Genetics, and Environmental Risk Exposure (NGERE); University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics; University of Lorraine - Reference Centre for Inborn Errors of Metabolism (ORPHA67872)

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Abstract

BACKGROUND: COVID-19 can induce pulmonary and systemic inflammation and subsequent multi-organ dysfunction. In patients with severe COVID-19, no data are available on the longitudinal evolution of biochemical abnormalities and their ability to predict disease outcomes.

METHODS: Using a retrospective, longitudinal cohort study design on consecutive patients with severe COVID-19, we monitored biomarker kinetics to estimate the occurrence of organ dysfunction and the severity of the inflammatory reaction and their association with acute respiratory failure (ARF) and death through multilevel modeling adapted for repeated measures.

FINDINGS: A total of 162 patients were assessed and did not receive antiviral therapy against SARS-CoV-2. During the study period, 1151 biochemical explorations were carried out for up to 59 biochemical markers in blood and urine, totaling 15,260 biochemical values. The spectrum of biochemical abnormalities and their kinetics were consistent with a multi-organ involvement, including lung, kidney, heart, liver (major cytolysis, cholestasis, conjugated hyperbilirubinemia), muscle (major cytolysis), and pancreas (hyperlipasemia) along with a severe inflammatory syndrome. On the 20 more representative biochemical markers (>250 iterations), only CRP >90 mg/L (odds ratio [OR] 6·87, 95% CI, 2·36–20·01) and urea nitrogen >0·36 g/L (OR 3·91, 95% CI, 1·15–13·29) were independently associated with the risk of ARF. Urea nitrogen >0·42 g/L was the only marker associated with the risk of COVID-19 related death. The proportion of patients who developed an acute kidney injury (AKI) stage 3, increased significantly during follow-up (0·9%, day 0; 21·4%, day 14; P <0·001).

INTERPRETATION: Our results point out the lack of the association between the inflammatory markers and the risk of death but rather highlight a significant association between renal dysfunction and the risk of COVID-19 related acute respiratory failure and death. Further studies should address the significance of acute kidney injury in the prediction of COVID-19 related death.

FUNDING: No funding.

DECLARATION OF INTERESTS: The authors who have taken part in this study declare that they do not have anything to disclose regarding conflicts of interest concerning this manuscript.

ETHICS APPROVAL STATEMENT: The “Nancy Biochemical Database” is registered at the French National Commission on Informatics and Liberty, CNIL, under the record N°1763197v0. The Ethics committee of the University Hospital of Nancy approved the study (ID: 2020/264).

Keywords: COVID-19; SARS-CoV-2; Biomarker Kinetics; Multi-organ involvement; Disease outcomes

Suggested Citation

Oussalah, Abderrahim and Gleye, Stanislas and Urmes, Isabelle Clerc and Laugel, Elodie and Barbé, Françoise and Orlowski, Sophie and Malaplate, Catherine and Aimone-Gastin, Isabelle and Caillierez, Beatrice Maatem and Merten, Marc and Jeannesson, Elise and Kormann, Raphaël and Olivier, Jean-Luc and Rodriguez-Guéant, Rosa-Maria and Namour, Farès and Bevilacqua, Sybille and Thilly, Nathalie and Losser, Marie-Reine and Kimmoun, Antoine and Frimat, Luc and Levy, Bruno and Gibot, Sébastien and Schvoerer, Evelyne and Gueant, Jean-Louis, Kinetics of Biomarkers Associated with Organ Dysfunction and Inflammatory Status and Their Association with Disease Outcomes in Severe COVID-19: A Longitudinal Cohort Study (6/9/2020). Available at SSRN: https://ssrn.com/abstract=3627243 or http://dx.doi.org/10.2139/ssrn.3627243

Abderrahim Oussalah (Contact Author)

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics ( email )

Nancy, F-54000
France
+33 3 83 68 32 92 (Phone)
+33 3 83 15 35 91 (Fax)

University of Lorraine - INSERM UMR_S 1256

Nancy, F-54000
France

Stanislas Gleye

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Isabelle Clerc Urmes

University of Lorraine - University Hospital of Nancy - Department of Methodology

Nancy, F-54000
France

Elodie Laugel

University of Lorraine - Nancy-Université

France

Françoise Barbé

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Sophie Orlowski

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Catherine Malaplate

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Isabelle Aimone-Gastin

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Beatrice Maatem Caillierez

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Marc Merten

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Elise Jeannesson

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Raphaël Kormann

University of Lorraine - University Hospital of Nancy - Department of Nephrology

Nancy, F-54000
France

Jean-Luc Olivier

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Rosa-Maria Rodriguez-Guéant

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Farès Namour

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics

Nancy, F-54000
France

Sybille Bevilacqua

University of Lorraine - University Hospital of Nancy - Department of Infectious Diseases

Nancy, F-54000
France

Nathalie Thilly

University of Lorraine - University Hospital of Nancy - Department of Methodology, Promotion and Investigation

Nancy, F-54000
France

Marie-Reine Losser

University of Lorraine - University Hospital of Nancy - Department of Anesthesiology and Intensive Care Medicine

Nancy, F-54000
France

Antoine Kimmoun

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

Nancy, F-54000
France

Luc Frimat

University of Lorraine - University Hospital of Nancy - Department of Nephrology

Nancy, F-54000
France

Bruno Levy

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

Nancy, F-54000
France

Sébastien Gibot

University of Lorraine - University Hospital of Nancy - Medical Intensive Care Unit

Nancy, F-54000
France

Evelyne Schvoerer

University of Lorraine - Department of Virology ( email )

Jean-Louis Gueant

University of Lorraine - Nutrition, Genetics, and Environmental Risk Exposure (NGERE) ( email )

Nancy
France

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics ( email )

Nancy, F-54000
France

University of Lorraine - Reference Centre for Inborn Errors of Metabolism (ORPHA67872) ( email )

Nancy, F-54000
France