Pediatric Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital, Cairo, Egypt
Nahla Elsharkawy
Clinical pathology department, National Cancer Institute, Cairo University and Children's Cancer Hospital, Cairo, Egypt
Mohamed El Ansary
Department of Intensive Care, Faculty of Medicine, Cairo University, Cairo, Egypt
Ahmed Al-Halfawy
Department of Pulmonary Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
Alaa Elhadad
Pediatric Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital, Cairo, Egypt
Ashraf Hatem
Department of Chest Diseases, Faculty of Medicine, Cairo University, Cairo, Egypt
Sherif Abouelnaga
Pediatric Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital, Cairo, Egypt
Laura L Dugan
Division of Geriatric Medicine, Department of Medicine, Vanderbilt University Medical Center; and VATennessee Valley Geriatric Research, Education and Clinical Center (GRECC), Nashville, United States
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.
