Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality

eLife

Nahla Elsharkawy¹  Ashraf Hatem²  Mohamed El Ansary³  Ahmed Al-Halfawy⁴  Laura L Dugan⁵  Riem M El-Messiery⁶  Alaa Elhadad⁷  Sherif Abouelnaga⁷  Mahmoud Hammad⁷  Basma A Yasseen⁸  Sameh Saad Ali⁸  Diaa Al-Raawi⁸  Mona Zidan⁸  Mohamed A Badawy⁸  Hajar El-sayed⁸  Azza G Kamel⁸  Rehab Hamdy⁸  Aya A Elkhodiry⁸  Asmaa M Shedra⁸  Engy A Abdel-Rahman⁹ 

[1] Clinical pathology department, National Cancer Institute, Cairo University and Children's Cancer Hospital, Cairo, Egypt;Department of Chest Diseases, Faculty of Medicine, Cairo University, Cairo, Egypt;Department of Intensive Care, Faculty of Medicine, Cairo University, Cairo, Egypt;Department of Pulmonary Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt;Division of Geriatric Medicine, Department of Medicine, Vanderbilt University Medical Center; and VATennessee Valley Geriatric Research, Education and Clinical Center (GRECC), Nashville, United States;Infectious Disease Unit, Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt;Pediatric Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital, Cairo, Egypt;Research Department, Children’s Cancer Hospital, Cairo, Egypt;Research Department, Children’s Cancer Hospital, Cairo, Egypt;Pharmacology Department, Faculty of Medicine, Assuit University, Assuit, Egypt;

关键词: critically ill COVID-19 patients;    COVID-19 mortality;    neutrophils;    oxidative stress;    human serum albumin damage;    Human;   

DOI  :  10.7554/eLife.69417

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10–11). Non-survivors’ 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 the transport function of HSA may be 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 μM, 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), log-rank χ2=12.1, p=4.9×10−4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.

【 授权许可】

CC BY