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.

Coronavirus Disease 2019 (COVID-19) had struck the world with health and economic catastrophes and recently with unusual autoimmune presentations, including new-onset Type 1 Diabetes. Herein we present a 17-year-old male patient who presented to the Emergency room with fever, palpitation, and cough of four-week duration; he was referred to the Emergency room and was found to have DKA. CT of the chest showed ground-glass opacities suggestive of COVID-19 pneumonia, and abdominal cuts showed dilated intrahepatic biliary radicles with pancreatic loculations suggestive of pancreatitis. The patient was admitted to the ICU, started on Intravenous fluids and Insulin infusion then COVID-19 PCR returned positive. We hypothesize that SARS-CoV-2 has a vital role in eliciting an autoimmune response triggering Type 1 Diabetes, and further studies are needed to confirm this hypothesis. SARS-COV-2 may cause pancreatitis, and the first presentation could be high blood sugar or DKA.

Roles of platelets during infections surpass the classical thrombus function and are now known to modulate innate immune cells. Leukocyte-platelet aggregations and activation-induced secretome are among factors recently gaining interest but little is known about their interplay with severity and mortality during the course of SARS-Cov-2 infection. The aim of the present work is to follow platelets’ bioenergetics, redox balance, and calcium homeostasis as regulators of leukocyte-platelet interactions in a cohort of COVID-19 patients with variable clinical severity and mortality outcomes. We investigated COVID-19 infection-related changes in platelet counts, activation, morphology (by flow cytometry and electron microscopy), bioenergetics (by Seahorse analyzer), mitochondria function (by high resolution respirometry), intracellular calcium (by flow cytometry), reactive oxygen species (ROS, by flow cytometry), and leukocyte-platelet aggregates (by flow cytometry) in non-intensive care unit (ICU) hospitalized COVID-19 patients (Non-ICU, n=15), ICU-survivors of severe COVID-19 (ICU-S, n=35), non-survivors of severe COVID-19 (ICU-NS, n=60) relative to control subjects (n=31). Additionally, molecular studies were carried out to follow gene and protein expressions of mitochondrial electron transport chain complexes (ETC) in representative samples of isolated platelets from the studied groups. Our results revealed that COVID-19 infection leads to global metabolic depression especially in severe patients despite the lack of significant impacts on levels of mitochondrial ETC genes and proteins. We also report that severe patients’ platelets exhibit hyperpolarized mitochondria and significantly lowered intracellular calcium, concomitantly with increased aggregations with neutrophil. These changes were associated with increased populations of giant platelets and morphological transformations usually correlated with platelets activation and inflammatory signatures, but with impaired exocytosis. Our data suggest that hyperactive platelets with impaired exocytosis may be integral parts in the pathophysiology dictating severity and mortality in COVID-19 patients.

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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.

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Introduction Insulin resistance and obesity have been associated with irisin, a protein in fat cells. The levels of irisin in patients with type 2 diabetes mellitus (T2DM) were significantly lower than those in non‐diabetics. This study aimed to examine the relationship between serum irisin levels and endothelial dysfunction in patients with T2DM. Methods There were 90 participants in this study. We matched 65 patients with T2DM with 25 healthy control participants. A series of tests were performed on the participants, including fasting blood glucose, 2 hours postprandial blood glucose, glycated haemoglobin, triglycerides (TG), total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), TG/HDL‐C ratio and albumin/creatinine ratio. In addition to measuring high‐sensitivity C‐reactive protein (hs‐CRP). Enzyme‐linked immunosorbent assay (ELISA) technique was used for estimating irisin concentrations. Results Flow‐mediated dilation (FMD) was significantly lower in patients with T2DM; however, there was a non‐statistically significant difference between healthy controls and patients with T2DM regarding serum Irisin level. CRP and LDL levels were inversely correlated with circulating irisin levels. In a stepwise regression analysis, only the hs‐CRP and LDL were statistically significant in predicting irisin level. Conclusions In patients with T2DM, serum levels of irisin were inversely correlated with hyperglycaemia, body mass index and per cent body fat; this suggests that detecting irisin levels early can prevent cardiovascular diseases from progressing. According to the study results, serum irisin serves as a predictive marker for early cardiovascular disease, thus preventing the disease from progressing. There is a need for further research in order to understand how irisin contributes to the development of atherosclerosis and the development of diabetic complications.