Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality
- Children's Cancer Hospital Egypt 57357, Egypt
- Cairo University, Egypt
- Vanderbilt University Medical Center, United States
Abstract
Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1-35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance (EPR) spectra of spin labelled fatty acids (SLFA) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivor' HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA we show that transport function of HSA maybe impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 mM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (< 0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), logrank c2 = 12.1, p=4.9x10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Raw data collected and used to produce all figures and tables are available on Dyrad (https://doi.org/10.5061/dryad.cnp5hqc4q).
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Data from: Biophysical Data Pertaining to COVID-19 caused human serum albumin damageDryad Digital Repository, doi:10.5061/dryad.cnp5hqc4q.
Article and author information
Author details
Funding
The Association of Friends of the National Cancer Institute (COVID-SA)
- Sameh Saad Ali
The Children's Cancer Hospital Egypt (SA-Start up)
- Sameh Saad Ali
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Written informed consents were obtained from participants in accordance with the principles of the Declaration of Helsinki. For COVID-19 and control blood/plasma collection, Children's Cancer Hospital's Institutional Review Board (IRB) has evaluated the study design and protocol, IRB number 31-2020 issued on July 6, 2020.
Copyright
© 2021, Badawy et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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