A predominance of type 1 inflammation was associated with severe COVID-19.
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COVID-19 patients had a high acute kidney injury or pulmonary fibrosis prevalence.
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Type 1 inflammation may contribute to multi-organ failure associated with 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 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.
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.
Graphical abstract
Keywords
COVID-19
Cytokine storm
ARDS
AKI
Fibrosis
Endotype
Abbreviations
ARDS
patients who already suffered from acute respiratory distress syndrome (ARDS) at the time of blood collection
pre-ARDS
patients who developed ARDS after blood collection
non-ARDS
patients who did not develop ARDS during the observation period
AKI
patients developed acute kidney injury (AKI)
pre-AKI
patients who developed AKI after blood collection
non-AKI
patients who did not develop AKI during the observation period