Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19
Marthe Jøntvedt Jørgensen, Jan Cato Holter, Erik Egeland Christensen, Camilla Schjalm, Kristian Tonby, Søren Erik Pischke, Synne Jenum, Linda Gail Skeie, Sarah Nur, Andreas Lind, Hanne Opsand, Tone Burvald Enersen, Ragnhild Grøndahl, Anne Pernille Hermann, Susanne Dudman, Fredrik Müller, Thor Ueland, Tom Eirik Mollnes, Pål Aukrust, Lars Heggelund, Aleksander Rygh Holten, Anne Ma Dyrhol‐Riise
Abstract
In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79-0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.