Protease inhibitor plasma concentrations associate with COVID-19 infection

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  • Nicholas R Medjeral-Thomas, Imperial Coll London, Imperial College London, UKDRI
  • ,
  • Anne Troldborg
  • Annette G Hansen
  • Rasmus Pihl
  • Candice L Clarke, Imperial Coll London, Imperial College London, UKDRI
  • ,
  • James E Peters, Imperial Coll London, Imperial College London, UKDRI
  • ,
  • David C Thomas, Fremantle Hospital, Centre for Inflammatory Bowel Disease, Fremantle, Imperial Coll London, Imperial College London, UKDRI, Renal and Transplant Centre, Imperial College Healthcare NHS Trust, London, UK., Imperial College Healthcare NHS Trust, Queen Marys Univ London, Queen Mary University London, University of London, Barts & London Sch Med & Dent
  • ,
  • Michelle Willicombe, Imperial Coll London, Imperial College London, UKDRI
  • ,
  • Yaseelan Palarasah, Syddansk University
  • ,
  • Marina Botto, Imperial Coll London, Imperial College London, UKDRI
  • ,
  • Matthew C Pickering, Imperial Coll London, Imperial College London, UKDRI
  • ,
  • Steffen Thiel

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 coronavirus disease 2019 (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, alpha2-macroglobulin, 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 C-reactive protein. Results were adjusted for repeated measures and multiple comparisons. Analysis of all available samples demonstrated lower plasma C1 esterase inhibitor and α2M and higher total ITIH4 in COVID-19 compared with dialysis controls. These differences were also seen in the first sample collected after COVID-19 diagnosis, a median of 4 days from diagnostic swab. Plasma ITIH4 levels were higher in severe than the non-severe COVID-19. Serum C-reactive protein correlated positively with plasma levels of antithrombin, intact ITIH4 and total ITIH4. In conclusion, plasma protease inhibitor concentrations are altered in COVID-19.

Original languageEnglish
JournalOxford open immunology
Pages (from-to)iqab014
Publication statusPublished - 7 Jul 2021

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© The Author(s) 2021. Published by Oxford University Press.

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