Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death

10.1101/2020.11.05.20223289

medRxiv

22nd February 2021

Contributing to research themes:

End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n=256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. 203 proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3) and epithelial injury (e.g. KRT19). Machine learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.

Author list:

* equal contributions
Author Affiliations
1) Centre for Inflammatory Disease, Dept of Immunology and Inflammation, Imperial College London.
2) Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
3) CRUK Cambridge Institute and Cambridge Institute for Medical Research, University of Cambridge.
4) MRC Biostatistics Unit, Forvie Way, University of Cambridge.
5) Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge.
6) Health Data Research UK, London, UK.

 

Jack Gisby*1, Candice L. Clarke*1,2, Nicholas Medjeral-Thomas*1,2, Talat H. Malik1, Artemis Papadaki1, Paige M. Mortimer1, Norzawani B. Buang1, Shanice Lewis1, Marie Pereira1, Frederic Toulza1, Ester Fagnano1, Marie-Anne Mawhin1, Emma E. Dutton1, Lunnathaya Tapeng1, Arianne C. Richard3, Paul D. W. Kirk4,5, Jacques Behmoaras1, Eleanor Sandhu1,2, Stephen P. McAdoo1,2, Maria F. Prendecki1,2, Matthew C. Pickering1, Marina Botto1, Michelle Willicombe*1,2, David C. Thomas*1,2, James E. Peters*1,6