Type 1 inflammatory endotype relates to low compliance, lung fibrosis, and severe complications in COVID-19.

Abstract

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease; approximately 5% of patients developing severe COVID-19. It is known that cytokine release is associated with disease severity, but the relationship between the different clinical phenotypes and inflammatory endotypes is not well understood. This study investigated the association between inflammatory biomarker-based endotypes and severe COVID-19 phenotypes. Interleukin (IL) -6, C-reactive protein (CRP), C-X-C motif chemokine (CXCL) 9, IL-18, C-C motif chemokine (CCL) 3, CCL17, IL-10, and vascular endothelial growth factor (VEGF) were measured in 57 COVID-19 patients, and their association with clinical characteristics was examined using a cluster analysis. Significantly higher blood levels of the eight inflammatory markers were noted in patients who developed acute respiratory distress syndrome (ARDS) than in those who did not develop ARDS (non-ARDS). Using a cluster analysis, the patient groups were classified into four clusters, of which two had patients with high IL-6 and CRP levels. In the cluster with high levels of Type 1 (T1) inflammatory markers such as CXCL9 and IL-18, 85% of the patients had ARDS, 65% of the patients developed acute kidney injury (AKI), and 78% of the patients developed pulmonary fibrosis. In the cluster with high levels of T1 inflammatory markers, the patients frequently suffered from tissue damage, manifested as ARDS and AKI. Our findings identified distinct T1 inflammatory endotypes of COVID-19 and suggest the importance of controlling inflammation by monitoring T1 biomarkers and treating accordingly to limit the severity of the disease.