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

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.

Neutrophil-mediated Oxidative Stress and Albumin Structural Damage Predict COVID-19-associated Mortality

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 25 patients who were followed up for a median of 12.5 days (1-35 days), among them 14 had died. Analyzing blood samples from patients and healthy individuals (n=10), 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-survivors HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and greater S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. 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<0.16, 80% (9/12) vs. S/W>0.16, 20% (2/10), p=0.008; plasma [H2O2]>7.1 μM, 83.3% (5/6) vs. 16.7% (1/6), p=0.049). 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 (< 0.0253) predicted mortality with 100% accuracy (100% (6/6) vs. 0% (0/6), logrank χ2 = 12.01, p = 5x10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements.

Kinetic and thermodynamic study of the interactions between human carbonic anhydrase variants and polystyrene nanoparticles of different size

The protein packing at the surface may increase as the size of particles decreases given the right particle–protein characteristics.

Study of influence of millimeter range electromagnetic waves on water–saline solutions of albumin

In this work, the effect of electromagnetic waves of millimeter diapason (EMW MM) on both melting parameters of serum albumin from human blood and its solution density has been studied. It was shown that the irradiation of albumin solution results in protein denaturation at higher temperatures than in the case of nonirradiated samples, which indicates the increase of albumin packing degree. It was also shown that the enhancement of albumin solution density takes place which indicates the protein packing degree change as well. The obtained data show that the effect of EMW MM does not depend on frequency of these waves, because alterations are revealed at all studied frequencies — 41.8, 48 and 51.8[Formula: see text]GHz.