Identification of a protein expression signature distinguishing early from organising diffuse alveolar damage in COVID-19 patients.

Abstract

Diffuse alveolar damage (DAD) is a histopathological finding associated with severe viral infections, including SARS-CoV-2. However, the mechanisms mediating progression of DAD are poorly understood. Applying protein digital spatial profiling to lung tissue obtained from a cohort of 27 COVID-19 autopsy cases from the UK, we identified a protein signature (ARG1, CD127, GZMB, IDO1, Ki67, phospho-PRAS40 (T246), and VISTA that distinguishes early / exudative DAD from late / organising DAD with good predictive accuracy. These proteins warrant further investigation as potential immunotherapeutic targets to modulate DAD progression and improve patient outcome.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was funded by UK Research and Innovations / NIHR UK Coronavirus Immunology Consortium (UK-CIC). PMK is also supported by a Wellcome Trust Senior Investigator Award (WT104726). OAB and JTHL were supported by Wellcome Trust Core Funding. The funders had no role in the design or conduct of the study of the decision to publish.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Human samples used in this research project were partly obtained from the Newcastle Hospitals CEPA Biobank and their use in research is covered by Newcastle Hospitals CEPA Biobank ethics REC 17/NE/0070. Additional human samples used in this research project were obtained from the Imperial College Healthcare Tissue Bank (ICHTB). ICHTB is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. ICHTB is approved by Wales REC3 to release human material for research (22/WA/0214). Additional human samples used in this research project were obtained from the ICECAP tissue bank of the University of Edinburgh. ICECAP is approved by the East of Scotland Research Ethics Service to release human material for research (16/ED/0084). Analysis of these samples at the University of York was approved by the Hull York Medical School Ethics Committee (20/52).

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Data Availability

Raw DSP count data are deposited at the Open Science Framework and are available at https://osf.io/69znm/

https://osf.io/69znm/

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