Erythrocytes identify complement activation in patients with COVID-19.
L K Metthew LamJohn P ReillyAnn H RuxSophia J MurphyLeticia Kuri-CervantesAriel R WeismanCaroline A G IttnerMaria Betina PampenaMichael R BettsE John WherryWen-Chao SongJohn D LambrisNuala J MeyerDouglas B CinesNilam S MangalmurtiPublished in: American journal of physiology. Lung cellular and molecular physiology (2021)
COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.
Keyphrases
- sars cov
- coronavirus disease
- septic shock
- acute kidney injury
- intensive care unit
- end stage renal disease
- respiratory syndrome coronavirus
- ejection fraction
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- stem cells
- respiratory failure
- prognostic factors
- risk factors
- endothelial cells
- atrial fibrillation
- type diabetes
- cardiovascular events
- bone marrow
- congenital heart disease
- binding protein