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

• DOI: 10.7554/elife.69417
• Publication Date: 2021-11-25T12:15:11Z
• Authors: Mohamed A Badawy; Basma A Yasseen; Riem M El-Messiery; Engy A Abdel-Rahman; Aya A Elkhodiry; Azza G Kamel; Hajar El-sayed; Asmaa M Shedra; Rehab Hamdy; Mona Zidan; Diaa Al-Raawi; Mahmoud Hammad; Nahla Elsharkawy; Mohamed El Ansary; Ahmed Al-Halfawy; Alaa Elhadad; Ashraf Hatem; Sherif Abouelnaga; Laura L Dugan; Sameh Saad Ali
• Keywords: Human serum albumin

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 linked mortality outcome 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 samples from healthy individuals (n=11), provide evidence neutrophils are major sources hydrogen peroxide highly accumulated plasmas non-survivors. then analyzed electron paramagnetic resonance spectra spin-labeled fatty acids (SLFAs) bound whole control, survivor, non-survivor subjects (n=10–11). Non-survivors’ showed dramatically reduced packing order parameter, faster SLFA correlational rotational time, smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid microenvironments. Following loading/unloading 16-DSA, show transport function may be impaired severe Stratified at means, Kaplan–Meier survival analysis indicated lower values H 2 O plasma significantly predicted in-hospital (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; [H ]>8.6 μM, 65.2% (15/23) 34.8% (8/23), p=0.043). When combined these two parameters as ((S/W)/[H ]) derive risk score, resultant score than mean (<0.019) high fidelity (95.5% (21/22) 4.5% (1/22), log-rank χ =12.1, p=4.9×10 −4 ). The derived surrogate marker assess new candidates COVID-19 treatments targeting replacements and/or stress.