The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients

• Published in: Nature communications Vol. 12; no. 1; p. 4888
• Main Authors: Perreau, Matthieu, Suffiotti, Madeleine, Marques-Vidal, Pedro, Wiedemann, Aurelie, Levy, Yves, Laouénan, Cédric, Ghosn, Jade, Fenwick, Craig, Comte, Denis, Roger, Thierry, Regina, Jean, Vollenweider, Peter, Waeber, Gerard, Oddo, Mauro, Calandra, Thierry, Pantaleo, Giuseppe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.08.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/127; 631/250/255/2514; 631/326/596/4130; 692/699/255/2514; 82/1; Anti-inflammatory agents; Chemokines; Coronaviruses; COVID-19; CXCL13 protein; Cytokines; Fibrosis; Growth factors; Hepatocyte growth factor; Humanities and Social Sciences; Immune response; Immune system; Immunology; Inflammation; Life Sciences; Lung diseases; Lungs; Markers; Mortality; multidisciplinary; Patients; Regulatory mechanisms (biology); Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25191-5

The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a ‘discovery’ cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts ( P  < 0.05 to P  < 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two ‘validation’ cohorts, i.e . the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients. Infection with SARS CoV2 results in the induction of multiple cytokine and inflammatory pathways. Here the authors demonstrate the association of HGF and CXCL13 production with increased severity and mortality in COVID-19 patients.