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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
More...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
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