ABSTRACT
The objective of the present study was to identify biological signatures of severe 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). While cellular immunological markers lacked power in discriminating between ICU and non-ICU patients, 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P<0.05 to P<0.001). 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). 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. The two cytokines in combination were the best predictors 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). 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.