ABSTRACT
IGF (Insulin-like Growth Factor) system proteins, including their ligands IGF1 and IGF2, their receptor IGF1R and binding proteins (IGFBPs) that control their bioavailability, are involved in pulmonary homeostasis and in respiratory diseases, including COVID-19. However, their circulating levels have not yet been studied comparatively between groups of patients with different degrees of severity of the disease in order to determine their possible value as biomarkers in this context. Serum levels of IGF1, IGF2 and IGF1R were determined by ELISA, and those of IGFBP2, IGFBP3, IGFBP4 and IGFBP5 by immunoblotting. Results were compared between three groups of patients with different degrees of severity of COVID-19, and with those of an uninfected control group (total n = 120): uninfected (n = 24), asymptomatic (n = 32), hospitalized (n = 32) and ICU (n = 32) controls. IGFBP3/IGFBP2 ratios were also quantified. While IGF1 and IGF2 levels decreased in hospitalized and ICU patients, IGF1R levels were increased in ICU patients. IGFBP2 levels were also elevated in ICU patients, and conversely, IGFBP3 and IGFBP5 levels and IGFBP3/IGFBP2 ratios tend to decrease progressively with the severity of the disease. IGFBP4 levels were only significantly increased in the hospitalized patients compared to the control group. Changes in concentration levels of IGF1, IGF2, IGFBP3, and IGFBP5 follow similar patterns with a downward trend with COVID-19 severity, and are opposite to those of IGF1R and IGFBP2. IGFBP4 shows a different profile, being higher in hospitalized patients. Serum levels of IGFs change with the degree of COVID-19 and decreasing IGFBP3 and IGFBP5 levels and IGFBP3/IGFBP2 ratios show up as candidate biomarkers of disease severity.