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.

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Background Alterations of heart rate variability (HRV) in epileptic patients were the field of interest of several studies for many reasons, particularly the contribution toward sudden unexpected death in epilepsy (SUDEP). Aim We aimed at evaluation of autonomic dysfunction in epileptic patients during awake and sleep in addition to studying the association between SUDEP risk with different Holter parameters. Patients and Methods The study included eighty epileptic patients (40 controlled epileptic patients and 40 refractory epileptic patients) compared to 30 volunteers as control group. They underwent detailed epileptic history, Chalfont seizure severity scale, sudden unexpected death in epilepsy (SUDEP)-7 risk score and 24 hour Holter monitoring to assess HRV parameters. Results Patients with refractory epilepsy had longer duration of epilepsy with increased number of used AEDs compared to controlled epileptic group. Both controlled and refractory epileptic patients had significantly higher average heart rate (AV.HR), sympatho-vagal ratio (low-frequency/high-frequency (LF/HF) ratio in 24 hours, daytime, and nighttime), and LF and HF values compared to controls. The rMSSD (the root mean square of difference between successive normal intervals), Tri.Index (triangular index), and pNN50 (percentage of the number of pairs of consecutive beat-to-beat intervals that varied by 50 ms) were significantly reduced in both epileptic groups compared to controls. Among refractory epileptic patients, patients with generalized epilepsy had significantly higher severity epileptic scale, average heart rate, minimum heart rate, and LF/HF night, in addition to lower rMSSD and pNN50 compared to patients with focal epilepsy. We found positive correlation between the following Holter indices (LF/HF 24, LF/HF day, and LF/HF night) and the duration of the epilepsy, while negative correlations between Tri.Index, LF, and HF and the epileptic duration were detected. SUDEP-7 risk was negatively correlated with pNN50 and rMSSD; meanwhile, it was positively correlated with LF/HF 24. The severity of epilepsy among refractory epileptic patients was positively correlated with average heart rate but negatively correlated with pNN50 and rMSSD. Using linear regression analysis, we found that pNN50 and rMSSD could predict SUDEP-7 risk and severity of epilepsy in refractory epileptic patients. Conclusion Epileptic patients (particularly refractory patients with generalized EEG findings and long duration) had reduced heart rate variability and hence impairment of parasympathetic activity with increased susceptibility for adverse outcomes. Moreover, pNN50 and rMSSD could be used as predictors for SUDEP-7 risk as well as severity of epilepsy in refractory epileptic patients.

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.