ABSTRACT
Acute and chronic kidney failure is common in hospitalized patients with COVID-19, yet the mechanism of injury and predisposing factors remain poorly understood. We investigated the role of complement activation by determining the levels of deposited complement components (C1q, C3, FH, C5b-9) and immunoglobulin along with the expression levels of the injury-associated molecules spleen tyrosine kinase (Syk), mucin-1 (MUC1) and calcium/calmodulin-dependent protein kinase IV (CaMK4) in the kidney tissues of people who succumbed to COVID-19. We report increased deposition of C1q, C3, C5b-9, total immunoglobulin, and high expression levels of Syk, MUC1 and CaMK4 in the kidneys of COVID-19 patients. Our study provides strong rationale for the expansion of trials involving the use of inhibitors of these molecules, in particular C1q, C3, Syk, MUC1 and CaMK4 to treat patients with COVID-19.
Subject(s)
COVID-19/metabolism , Complement System Proteins/metabolism , Kidney/metabolism , Mucin-1/metabolism , SARS-CoV-2 , Syk Kinase/metabolism , Aged , Aged, 80 and over , COVID-19/pathology , Calcium-Calmodulin-Dependent Protein Kinase Type 4/genetics , Calcium-Calmodulin-Dependent Protein Kinase Type 4/metabolism , Complement System Proteins/genetics , Fatal Outcome , Female , Gene Expression Regulation , Humans , Male , Middle Aged , Mucin-1/genetics , Syk Kinase/geneticsABSTRACT
Lung inflammation and damage is prominent in people infected with SARS-Cov-2 and a major determinant of morbidity and mortality. We report the deposition of complement components in the lungs of people who succumbed to COVID-19 consistent with the activation of the classical and the alternative pathways. Our study provides strong rationale for the expansion of trials involving the use of complement inhibitors to treat patients with COVID-19.