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07.03.2022

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

Abstract

Background: 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

Objective: This study investigated the association between inflammatory biomarker-based endotypes and severe COVID-19 phenotypes.

Methods: 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.

Results: Significantly higher blood levels of the eight inflammatory markers were noted in patients who devel- oped 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 pa- tients developed pulmonary fibrosis.

Conclusions: 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.


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