Protease inhibitor plasma concentrations associate with COVID-19 infection
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Author(s)
Type
Journal Article
Abstract
Protease inhibitors influence a range of innate immunity and inflammatory pathways. We quantified plasma concentrations of key anti-inflammatory protease inhibitors in chronic haemodialysis patients with COVID-19. The samples were collected early in the disease course to determine whether plasma protease inhibitor levels associated with the presence and severity of COVID-19. We used antibody-based immunoassays to measure plasma concentrations of C1 esterase inhibitor (C1-INH), alpha2-macroglobulin (α2M), antithrombin, and inter-alpha-inhibitor heavy chain 4 (ITIH4) in 100 serial samples from 27 haemodialysis patients with COVID-19. ITIH4 was tested in two assays, one measuring intact ITIH4 and another also detecting any fragmented ITIH4 (total ITIH4). Control cohorts were 32 haemodialysis patients without COVID-19 and 32 healthy controls. We compared protease inhibitor concentration based on current and future COVID-19 severity and with CRP. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1-INH and α2M and higher total ITIH4 in COVID-19 compared to dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of four days from diagnostic swab. Plasma ITIH4 levels were higher in severe than non-severe COVID-19. Serum CRP correlated positively with plasma levels of antithrombin, intact ITIH4, and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.
Date Issued
2021-07-07
Date Acceptance
2021-07-02
ISSN
2633-6960
Publisher
Oxford University Press
Journal / Book Title
Oxford Open Immunology
Volume
2
Issue
1
Copyright Statement
CThe Author(s) 2021. Published by Oxford University Press.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/),which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URI
Sponsor
Medical Research Council (MRC)
Wellcome Trust
Grant Number
MR/V027638/1
212252/Z/18/Z
Publication Status
Published online
Article Number
ARTN iqab014