Analysis of the COVID-19 Lockdown Impact on Biological Parameters and Physical Performance in Football Players

The COVID-19 pandemic has caused significant changes in global sustainability, but specifically, this study analyses the impact of lockdown on health and behavior in the game of football. The 2020/2021 Italian football competitive season (indicated as "post-COVID”), taking place following an obliged lockdown and longer than the normal summery season break, was characterized by very short recovery times and was compared to the 2018–2019 "pre-COVID” season, which had a regular course. The comparisons were about anthropometric and hormonal responses, muscle damage, and the physical performance of players in the major league (Serie A), and were made considering two extreme points of the competitive seasons: before the preparatory period (T0) and at the end of the season (T1). Turning to the results, it is significant to note the following: (1) body fat percentage was lower at the start (T0) of the post-COVID season than at the start of the pre-COVID season. During both seasons, serum CK and LDH increased in T1 and were significantly higher in both T0 and T1 of the post-COVID season. (2) Cortisol and testosterone concentrations increased in both seasons from T0 to T1;however, in the post-COVID season, concentrations of both were higher than in the previous season. The testosterone to cortisol ratio increased at the end of the pre-COVID season, whilst strongly decreasing at T1 of the post-COVID season. (3) Blood lactate concentrations significantly decreased during the pre-COVID season but remained unchanged during the post-COVID season. We may conclude that the enforced suspension period and the consequent rapid resumption of all activities influenced the physical and physiological state of professional footballers.

An Effective Threat Detection Framework for Advanced Persistent Cyberattacks

Recently, with the normalization of non-face-to-face online environments in response to the COVID-19 pandemic, the possibility of cyberattacks through endpoints has increased. Numerous endpoint devices are managed meticulously to prevent cyberattacks and ensure timely responses to potential security threats. In particular, because telecommuting, telemedicine, and tele-education are implemented in uncontrolled environments, attackers typically target vulnerable endpoints to acquire administrator rights or steal authentication information, and reports of endpoint attacks have been increasing considerably. Advanced persistent threats (APTs) using various novel variant malicious codes are a form of a sophisticated attack. However, conventional commercial antivirus and anti-malware systems that use signature-based attack detection methods cannot satisfactorily respond to such attacks. In this paper, we propose a method that expands the detection coverage in APT attack environments. In this model, an open-source threat detector and log collector are used synergistically to improve threat detection performance. Extending the scope of attack log collection through interworking between highly accessible open-source tools can efficiently increase the detection coverage of tactics and techniques used to deal with APT attacks, as defined by MITRE Adversarial Tactics, Techniques, and Common Knowledge (ATT&CK). We implemented an attack environment using an APT attack scenario emulator called Carbanak and analyzed the detection coverage of Google Rapid Response (GRR), an open-source threat detection tool, and Graylog, an open-source log collector. The proposed method expanded the detection coverage against MITRE ATT&CK by approximately 11% compared with that conventional methods. © 2023 Tech Science Press. All rights reserved.

Effect of geographical factors on reference values of creatine kinase isoenzyme.

The aim of this study was to investigate the geographical spatial distribution of creatine kinase isoenzyme (CK-MB) in order to provide a scientific basis for clinical examination. The reference values of CK-MB of 8697 healthy adults in 137 cities in China were collected by reading a large number of literates. Moran index was used to determine the spatial relationship, and 24 factors were selected, which belonged to terrain, climate, and soil indexes. Correlation analysis was conducted between CK-MB and geographical factors to determine significance, and 9 significance factors were extracted. Based on R language to evaluate the degree of multicollinearity of the model, CK-MB Ridge model, Lasso model, and PCA model were established, through calculating the relative error to choose the best model PCA, testing the normality of the predicted values, and choosing the disjunctive kriging interpolation to make the geographical distribution. The results show that CK-MB reference values of healthy adults were generally correlated with latitude, annual sunshine duration, annual mean relative humidity, annual precipitation amount, and annual range of air temperature and significantly correlated with annual mean air temperature, topsoil gravel content, topsoil cation exchange capacity in clay, and topsoil cation exchange capacity in silt. The geospatial distribution map shows that on the whole, it is higher in the north and lower in the south, and gradually increases from the southeast coastal area to the northwest inland area. If the geographical factors are obtained in a location, the CK-MB model can be used to predict the CK-MB of healthy adults in the region, which provides a reference for us to consider regional differences in clinical diagnosis.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Performance evaluation of a fast and efficient intrusion detection framework for advanced persistent threat-based cyberattacks

After the COVID-19 pandemic, cyberattacks are increasing as non-face-to-face environments such as telecommuting and telemedicine proliferate. Cyberattackers exploit vulnerabilities in remote systems and endpoint devices in major enterprises and infrastructures. To counter these attacks, fast detection and response are essential because advanced persistent threat (APT) attacks intelligently infiltrate endpoint devices for long periods and spread to large-scale environments. However, because conventional security systems are signature-based, fast detection of APT attacks is challenging, and it is difficult to respond flexibly to the environment. In this study, we propose an APT fast detection and response technique using open-source tools that improves the efficiency of existing endpoint information protection systems and swiftly detects the APT attack process. Performance test results based on realistic scenarios using the open-source APT attack library and MITER ATT&CK indicated that fast detection was possible with higher accuracy for the early stages of APT attacks in scenarios where endpoint attack detectors are interworking environments. © 2022 The Authors

Synthesis and Crystal Structure of Adamantylated 4,5,6,7-Tetrahalogeno-1H-benzimidazoles Novel Multi-Target Ligands (Potential CK2, M2 and SARS-CoV-2 Inhibitors); X-ray/DFT/QTAIM/Hirshfeld Surfaces/Molecular Docking Study.

A series of new congeners, 1-[2-(1-adamantyl)ethyl]-1H-benzimidazole (AB) and 1-[2-(1-adamantyl)ethyl]-4,5,6,7-tetrahalogeno-1H-benzimidazole (Hal=Cl, Br, I; tClAB, tBrAB, tIAB), have been synthesized and studied. These novel multi-target ligands combine a benzimidazole ring known to show antitumor activity and an adamantyl moiety showing anti-influenza activity. Their crystal structures were determined by X-ray, while intermolecular interactions were studied using topological Bader's Quantum Theory of Atoms in Molecules, Hirshfeld Surfaces, CLP and PIXEL approaches. The newly synthesized compounds crystallize within two different space groups, P-1 (AB and tIAB) and P21/c (tClAB and tBrAB). A number of intramolecular hydrogen bonds, C-H⋯Hal (Hal=Cl, Br, I), were found in all halogen-containing congeners studied, but the intermolecular C-H⋯N hydrogen bond was detected only in AB and tIAB, while C-Hal⋯π only in tClAB and tBrAB. The interplay between C-H⋯N and C-H⋯Hal hydrogen bonds and a shift from the strong (C-H⋯Cl) to the very weak (C-H⋯I) attractive interactions upon Hal exchange, supplemented with Hal⋯Hal overlapping, determines the differences in the symmetry of crystalline packing and is crucial from the biological point of view. The hypothesis about the potential dual inhibitor role of the newly synthesized congeners was verified using molecular docking and the congeners were found to be pharmaceutically attractive as Human Casein Kinase 2, CK2, inhibitors, Membrane Matrix 2 Protein, M2, blockers and Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, inhibitors. The addition of adamantyl moiety seems to broaden and modify the therapeutic indices of the 4,5,6,7-tetrahalogeno-1H-benzimidazoles.

Lead optimization, pharmacophore development and scaffold design of protein kinase CK2 inhibitors as potential COVID-19 therapeutics.

Therapeutic agents being designed against COVID-19 have targeted either the virus directly or the host cellular machinery. A particularly attractive host target is the ubiquitous and constitutively active serine-threonine kinase, Protein kinase CK2 (CK2). CK2 enhances viral protein synthesis by inhibiting the sequestration of host translational machinery as stress granules and assists in viral egression via association with the N-protein at filopodial protrusions of the infected cell. CK2 inhibitors such as Silmitasertib have been proposed as possible therapeutic candidates in COVID-19 infections. The present study aims to optimize Silmitasertib, develop pharmacophore models and design unique scaffolds to modulate CK2. The lead optimization phase involved the generation of compounds structurally similar to Silmitasertib via bioisostere replacement followed by a multi-stage docking approach to identify drug-like candidates. Molecular dynamics (MD) simulations were performed for two promising candidates (ZINC-43206125 and PC-57664175) to estimate their binding stability and interaction. Top scoring candidates from the lead optimization phase were utilized to build ligand-based pharmacophore models. These models were then merged with structure-based pharmacophores (e-pharmacophores) to build a hybrid hypothesis. This hybrid hypothesis was validated against a decoy set and used to screen a diverse kinase inhibitors library to identify favored chemical features in the retrieved actives. These chemical features include; an anion, an aromatic ring and an H-bond acceptor. Based on the knowledge of these features; de-novo scaffold design was carried out which identified phenindiones, carboxylated steroids, macrocycles and peptides as novel scaffolds with the potential to modulate CK2.Communicated by Ramaswamy H. Sarma.

Performance evaluation of a fast and efficient intrusion detection framework for advanced persistent threat-based cyberattacks

After the COVID-19 pandemic, cyberattacks are increasing as non-face-to-face environments such as telecommuting and telemedicine proliferate. Cyberattackers exploit vulnerabilities in remote systems and endpoint devices in major enterprises and infrastructures. To counter these attacks, fast detection and response are essential because advanced persistent threat (APT) attacks intelligently infiltrate endpoint devices for long periods and spread to large-scale environments. However, because conventional security systems are signature-based, fast detection of APT attacks is challenging, and it is difficult to respond flexibly to the environment. In this study, we propose an APT fast detection and response technique using open-source tools that improves the efficiency of existing endpoint information protection systems and swiftly detects the APT attack process. Performance test results based on realistic scenarios using the open-source APT attack library and MITER ATT&CK indicated that fast detection was possible with higher accuracy for the early stages of APT attacks in scenarios where endpoint attack detectors are interworking environments.

Association between the levels of muscle-specific creatinine kinase (CK-MM) and the incidence of persistent myalgia in COVID-19 survivors

Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) infection, may result in musculoskeletal tissue injury and is assumingly regulated through central and peripheral pathways. Muscle-specific creatinine kinase (CK-MM) is a specific biomarker used to indicate the presence of musculoskeletal tissue damage. This study aimed to investigate the correlation between the levels of CK-MM and the incidence of persistent myalgia in patients with post-COVID-19 syndromes.Methods: A cross-sectional study was conducted among COVID-19 survivors at the Faculty of Medicine and Clinical Pathology Laboratory, Universitas Airlangga, Surabaya from June - August 2022. The degree of pain of the myalgia was assessed using a visual analog scale (VAS), while CK-MM level was measured using a sandwich enzyme-linked immunosorbent assay (ELISA). Pearson correlation test at alpha=0.05 was used to identify the correlation between the levels of CK-MM and the incidence of persistent myalgia in patients with post-COVID-19 syndromes.Results: A total of 84 participants were enrolled in the study and half (50%) of them reported persistent myalgia postCOVID-19 recovery. Fatigue was the patients' most common persistent symptom (63%). Of the total 42 patients with persistent myalgia, more than half (56%) had mild pain intensity (VAS score: 1-3), and almost all of them (41 patients) experienced myalgia during the COVID-19 diagnosis. All the patients with post-COVID-19 myalgia had normal levels of CK-MM (mean: 32.7 ng/mL;range: 12-93 ng/mL), suggesting no musculoskeletal tissue damage. Anova test suggested no significant different of CK-MM levels between those with and without myalgia in patients with post-COVID-19 syndromes p=0.054).Conclusion: There was no significant association between CK-MM levels and the incidence of persistent myalgia in patients with post-COVID-19 syndromes.

Abnormal myocardial enzymes in the prediction of mortality and hypertension in COVID-19 patients: a retrospective study.

This study aims to determine the differences in myocardial enzymes in COVID-19 patients with and without hypertension. A total of 130 patients with COVID-19 in Yunmeng County People's Hospital were analyzed. The clinical manifestations and laboratory indicators were collected and analyzed. We found that COVID-19 patients with hypertension had higher mortality rate, greater age, and higher rates of basic disease such as diabetes than patients without hypertension. The γ-glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), albumin/globulin (A/G), Ca, Mg, lactate dehydrogenase (LDH), and α-hydroxybutyric-dehydrogenase (α-HBD) levels in COVID-19 patients with hypertension were higher than in COVID-19 patients without hypertension. We found that the predictive effect of the creatine kinase isoenzyme (CK-MB), LDH-L, and α-HBD levels in the COVID-19 patients without hypertension were higher than in COVID-19 patients with hypertension. We used the ROC curve model to predict whether patients would have hypertension, and we found that CK-MB, LDH-L and HBD parameters could distinguish the COVID-19 patients with hypertension and non-hypertension, and could predict the mortality of COVID-19 patients.

Severity and Mortality Predictors of COVID-19 Patients with Thrombotic Events-Evidence from the "COVID-One" Hospital in Albania.

COVID-19 vaccination leads to lower infection, morbidity, and mortality rates. However, COVID-19 infection leads to the development of coagulopathy-related manifestations in the form of both venous and arterial thromboembolism. This study aimed to assess the severity and mortality predictors of COVID-19 patients with thrombotic events in hospitalized patients in Albania. This is a retrospective study conducted in the "Mother Tereza" University Hospital of Tirana. Data were retrieved from the electronic databases of the hospital and only COVID-19 cases admitted to the infectious department during August-December 2020 were selected. Patients who, at admission, had a C-reactive protein (CRP) (mg/L) more than double and a D-dimer (ng/mL) more than triple according to international standards were included in the study. We performed univariate and multivariable logistic regression analysis, calculating unadjusted and adjusted odds ratios (ORs). A p-value < 0.05 was considered statistically significant. The study population included 60 hospitalized persons with a mean age of 64.4 years. Increased lactate dehydrogenase (LDH) (OR = 2.93; 95% CI = 0.82-10.42, p-value = 0.1) and increased creatine kinase (CK) (OR = 2.17; 95% CI = 0.63-7.46, p-value = 0.22) were related with increased probability of death. Moreover, a decreased number of lymphocytes was associated with increased mortality but with no statistical significance (OR = 0.40; 95% CI = 0.11-1.40, p-value = 0.15). The survival rate was higher for patients without comorbidities (p = 0.045). These results could serve as a baseline and as a reference for healthcare personnel who provides services to hospitalized patients with COVID-19. Further studies should take into consideration the vaccination of the population as well as including more hospitals and patients.

Crystal structure of the Rho-associated coiled-coil kinase 2 inhibitor belumosudil bound to CK2α.

The small molecule belumosudil was initially identified as a selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2) and has recently been approved for the treatment of graft-versus-host disease. However, recent studies have shown that many of the phenotypes displayed upon treatment with belumosudil were due to CK2α inhibition. CK2α is in itself a very promising therapeutic target for a range of conditions and has recently been put forward as a potential treatment for COVID-19. Belumosudil presents a promising starting point for the development of future CK2α inhibitors as it provides a safe, potent and orally bioavailable scaffold. Therefore, several of the major hurdles in drug development have already been overcome. Here, the crystal structure of belumosudil bound to the ATP site of CK2α is presented. This crystal structure combined with modelling studies further elucidates how belumosudil could be developed into a selective and potent CK2α or ROCK2 inhibitor.

Anti-adipogenic and Pro-lipolytic Effects on 3T3-L1 Preadipocytes by CX-4945, an Inhibitor of Casein Kinase 2.

Casein kinase 2 (CK2) is a ubiquitously expressed serine/threonine kinase and is upregulated in human obesity. CX-4945 (Silmitasertib) is a CK2 inhibitor with anti-cancerous and anti-adipogenic activities. However, the anti-adipogenic and pro-lipolytic effects and the mode of action of CX-4945 in (pre)adipocytes remain elusive. Here, we explored the effects of CX-4945 on adipogenesis and lipolysis in differentiating and differentiated 3T3-L1 cells, a murine preadipocyte cell line. CX-4945 at 15 µM strongly reduced lipid droplet (LD) accumulation and triglyceride (TG) content in differentiating 3T3-L1 cells, indicating the drug's anti-adipogenic effect. Mechanistically, CX-4945 reduced the expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and perilipin A in differentiating 3T3-L1 cells. Strikingly, CX-4945 further increased the phosphorylation levels of cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) while decreasing the intracellular ATP content in differentiating 3T3-L1 cells. In differentiated 3T3-L1 cells, CX-4945 had abilities to stimulate glycerol release and elevate the phosphorylation levels of hormone-sensitive lipase (HSL), pointing to the drug's pro-lipolytic effect. In addition, CX-4945 induced the activation of extracellular signal-regulated kinase-1/2 (ERK-1/2), and PD98059, an inhibitor of ERK-1/2, attenuated the CX4945-induced glycerol release and HSL phosphorylation in differentiated 3T3-L1 cells, indicating the drug's ERK-1/2-dependent lipolysis. In summary, this investigation shows that CX-4945 has strong anti-adipogenic and pro-lipolytic effects on differentiating and differentiated 3T3-L1 cells, mediated by control of the expression and phosphorylation levels of CK2, C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, AMPK, LKB-1, ERK-1/2, and HSL.

Mechanism of CK2 Inhibition by a Ruthenium-Based Polyoxometalate.

CK2 is a Ser/Thr protein kinase involved in many cellular processes such as gene expression, cell cycle progression, cell growth and differentiation, embryogenesis, and apoptosis. Aberrantly high CK2 activity is widely documented in cancer, but the enzyme is also involved in several other pathologies, such as diabetes, inflammation, neurodegeneration, and viral infections, including COVID-19. Over the last years, a large number of small-molecules able to inhibit the CK2 activity have been reported, mostly acting with an ATP-competitive mechanism. Polyoxometalates (POMs), are metal-oxide polyanionic clusters of various structures and dimensions, with unique chemical and physical properties. POMs were identified as nanomolar CK2 inhibitors, but their mechanism of inhibition and CK2 binding site remained elusive. Here, we present the biochemical and biophysical characterizing of the interaction of CK2α with a ruthenium-based polyoxometalate, [Ru4(µ-OH)2(µ-O)4(H2O)4 (γ-SiW10O36)2]10- (Ru4POM), a potent inhibitor of CK2. Using analytical Size-Exclusion Chromatography (SEC), Isothermal Titration Calorimetry (ITC), and SAXS we were able to unravel the mechanism of inhibition of Ru4POM. Ru4POM binds to the positively-charged substrate binding region of the enzyme through electrostatic interactions, triggering the dimerization of the enzyme which consequently is inactivated. Ru4POM is the first non-peptide molecule showing a substrate-competitive mechanism of inhibition for CK2. On the basis of SAXS data, a structural model of the inactivated (CK2α)2(Ru4POM)2 complex is presented.

Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells).

Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines by the innate immune system at a given time. One of these products is the drug PRS CK STORM, a medium conditioned by allogenic M2-polarized macrophages, from coculture, with those macrophages M2 with MSC from fat, whose composition, in vitro safety, and efficacy we studied. In the present work, we publish the results obtained in terms of safety (pharmacodynamics and pharmacokinetics) and efficacy of the intravenous application of this biological drug in a murine model of cytokine storm associated with severe infectious processes, including those associated with COVID-19. The results demonstrate the safety and high efficacy of PRS CK STORM as an intravenous drug to prevent and treat the cytokine storm associated with infectious processes, including COVID-19.

Skeletal Muscle Manifestations and Creatine Kinase in COVID-19.

Background and Purpose: Skeletal muscle symptoms and elevated creatine kinase (CK) levels have been consistently reported as part of the COVID-19 disease process. Previous studies have yet to show a consistent relationship between CK levels and skeletal muscle symptoms, disease severity, and death from COVID-19. The purpose of this study is to determine whether elevated CK is associated with a COVID-19 course requiring intubation, intensive care, and/or causing death. Secondary objectives: To determine if there is a relationship between elevated CK and (1) skeletal muscle symptoms/signs (2) complications of COVID-19 and (3) other diagnostic laboratory values. Methods: This is a retrospective, single center cohort study. Data were collected from March 13, 2020, to May 13, 2020. This study included 289 hospitalized patients with laboratory-confirmed SARS-CoV-2 and measured CK levels during admission. Results: Of 289 patients (mean age 68.5 [SD 13.8] years, 145 [50.2%] were men, 262 [90.7%] were African American) with COVID-19, 52 (18.0%) reported myalgia, 92 (31.8%) reported subjective weakness, and 132 (45.7%) had elevated CK levels (defined as greater than 220 U/L). Elevated CK was found to be associated with severity of disease, even when adjusting for inflammatory marker C-reactive protein (initial CK: OR 1.006 [95% CI: 1.002-1.011]; peak CK: OR 1.006 [95% CI: 1.002-1.01]; last CK: 1.009 [95% CI: 1.002-1.016]; q = .04). Creatine kinase was not found to be associated with skeletal muscle symptoms/signs or with other laboratory markers. Conclusions: Creatine kinase is of possible clinical significance and may be used as an additional data point in predicting the trajectory of the COVID-19 disease process.

Acute Neurological Manifestations of COVID-19 Patients From Three Tertiary Care Hospitals in Qatar.

Introduction Worldwide, there are more than 424 million confirmed cases of COVID-19. Most of the hospitalized critical COVID-19 patients manifested neurological signs and symptoms and higher mortality. The majority of COVID-19 fatalities occurred mostly in patients with advanced age and underlying medical comorbidities. This is the first local retrospective study in Qatar, which reported neurologic manifestations (48.5%) of hospitalized COVID-19 patients. The primary objective of this study is to evaluate acute neurological manifestations in COVID-19 hospitalized patients in the country. Methods This is a retrospective, observational study of 413 hospitalized COVID-19 patients. They were admitted to three different COVID-19 designated hospitals (Hazm Mebaireek, Ras Laffan, and Cuban tertiary care Hospitals) under the Hamad Medical Corporation, Qatar from 1st January 2020, to 31 January 2021. We evaluated electronic medical records of these patients and data were collected while their neurological manifestations were confirmed by two trained neurologists. These neurologic manifestations were categorized into three major groups: central nervous system (CNS), peripheral nervous system (PNS), and neuromuscular system. Results Of 413 patients, 94% (389) were male and 6% (24) were female; the mean age was 52 years. Among all different nationalities of COVID-19 patients, 20.3% (84) were Indian, 12.5% (52) were Bangladeshi, 10.1% (42) were Qatari and 9.2% (38) were Nepali. The most common symptoms at the onset of COVID-19 illness were as follows: 77.5% (321) had a fever, 67.4% (279) experienced cough, 58.7% (243) experienced shortness of breath and 26.1% (108) developed a sore throat. Overall 48.5% (201) patients developed different neurologic manifestations. The most common neurologic symptoms were myalgia (28%; 116), headache (10.4%; 43), dizziness (5.8%; 24) and hemiparesis due to strokes (5.3%; 22). In this study, the most common risk factors were hypertension (47.6%), diabetes (46.9%), obesity (21%), chronic kidney disease (10%), ischemic heart disease (9.7%), and smoking (6.8%). About 45.2% (187) patients were admitted to MICU and 8.5% (35) died due to COVID-19 complications. Significant other extrapulmonary multiorgan system involvement were skeletal muscle injury (39.4%), kidney injury (36.7%), liver injury (27.5%), myocardial injury (23.9%), rhabdomyolysis (15.7%) heart failure (11.4%) and acute pancreatitis (11.1%). Discussion The most common neurologic signs and symptoms were myalgia, headache, dizziness, and strokes, mainly due to large vessel thrombosis, lacunar, and posterior circulation strokes. Conclusions Patients with COVID-19 are at high risk of developing neurological manifestations. The most common COVID-19-related acute neurological manifestations were myalgia, headache, dizziness, and acute ischemic stroke. Prompt recognition, early diagnosis, and appropriate management of these manifestations could potentially lead to better patient outcomes in COVID-19 patients.

Evaluation of Liver Histopathological Findings of Coronavirus Disease 2019 by Minimally Invasive Autopsies.

AIM: The severe acute respiratory syndrome coronavirus 2 outbreak resulted in severe health impact with the loss of many lives across the world. Pulmonary parenchyma suffers the most from the brunt of the infection. However, evidence suggested a systemic involvement during the course of illness. Information on morphological changes of the liver is sparse in the literature. We aimed to evaluate the pathological findings in the liver by minimally invasive autopsies. METHODS: Postmortem core biopsies of the liver obtained from patients who succumbed to coronavirus disease 2019 disease were studied. Demographic findings, comorbidities, and relevant laboratory tests were collected. Detailed histopathological changes were assessed. RESULTS: Liver function tests were available in 40 cases, and it was deranged in 80% cases. A spectrum of histological changes was observed. Macrovesicular steatosis and nonspecific portal inflammation of mild degree were the common morphological changes. Features suggestive of vascular alteration were noted in more than half of the cases. These included increased portal vein branches, irregular luminal dilation, and herniation of portal veins into the periportal hepatocytes. In addition, we observed morphological changes attributed to terminal shock-related changes. CONCLUSION: The present study results highlight that liver parenchyma changes may be related to multiple pathogenic mechanisms. The presence of vascular alteration in portal tracts suggests derangement of hepatic vasculature related to systemic hypercoagulable state induced by the viral infection. It remains to be established if the histological changes are related to direct viral insult or to the systemic response caused by the viral attack.