Interleukin 6, soluble interleukin 2 receptor alpha (CD25), monocyte colony-stimulating factor, and hepatocyte growth factor linked with systemic hyperinflammation, innate immunity hyperactivation, and organ damage in COVID-19 pneumonia

Background: Patients infected by SARS-CoV-2 can develop interstitial pneumonia, requiring hospitalisation or mechanical ventilation. Increased levels of inflammatory biomarkers are associated with development of acute respiratory distress syndrome (ARDS). The aim of the present study was to determine which cytokines are associated with respiratory insufficiency in patients hospitalised for COVID-19. Patients and methods: Data on 67 consecutive patients were collected between March 8 and March 30, 2020. PaO2/FiO(2) ratio (P/F) was calculated at hospital admission. The following cytokines were analysed: interleukin (IL)-6, IL-1 alpha, IL-18, tumour necrosis factor (TNF)-beta, macrophage colony-stimulating factor (M-CSF), macrophage migration inhibitory factor (MIF), soluble IL-2 receptor alpha (sIL-2R alpha; CD25), IL-12 beta, IL-3, interferon (IFN) alpha 2a, monokine induced by gamma interferon (MIG), monocyte-chemotactic protein 3 (MCP3) and hepatocyte growth factor (HGF). Results: P/F lower than 300 was recorded in 22 out of 67 patients (32.8%). P/F strongly correlated with IL-6 (r = -0.62, P < 0.0001), M-CSF (r = -0.63, P < 0.0001), sIL-2R alpha (r = -0.54, P < 0.0001), and HGF (r = -0.53, P < 0.0001). ROC curve analyses for IL-6 (AUC 0.83, 95% CI 0.73-0.93, P < 0.0001), M-CSF (AUC 0.87, 95% CI 0.79-0.96, P < 0.0001), HGF (AUC 0.81, 95% CI 0.70-0.93, P < 0.0001), and sIL-2R alpha (AUC 0.80, 95% CI, 0.69-0.90, P < 0.0001) showed that these four soluble factors were highly significant. All four soluble factors correlated with LDH, white blood cell count, neutrophil count, lymphocyte count, and CRP. Conclusion: IL-6, M-CSF, sIL-2R alpha and HGF are possibly involved in the main biological processes of severe COVID-19, mirroring the level of systemic hyperinflammatory state, the level of lung inflammation, and the severity of organ damage.

Automated summary

In this study involving 67 hospitalized COVID-19 patients, IL-6, M-CSF, sIL-2R alpha, and HGF were found to be closely associated with respiratory insufficiency, indicating their potential involvement in the main biological processes of severe COVID-19.