Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of the Czech Republic and compared it with the course of the disease in patients treated with amiodarone in two major Prague's hospitals. In the whole population of the Czech Republic SARS-CoV-2 infected 1665070 persons (15.6 %) out of 10694000 (100 %) between 1 April 2020 and 30 June 2021. In the same time period only 35 patients (3.4 %) treated with amiodarone were infected with SARS-CoV-2 virus out of 1032 patients (100 %) who received amiodarone. It appears that amiodarone can prevent SARS-CoV-2 virus infection by multiple mechanisms. In in-vitro experiments it exhibits SARS-CoV-2 virus replication inhibitions. Due to its anti-inflammatory and antioxidant properties, it may have beneficial effect on the complications caused by SARS-CoV-2 as well. Additionally, inorganic iodine released from amiodarone can be converted to hypoiodite (IO-), which has antiviral and antibacterial activity, and thus can affect the life cycle of the virus.

• MeSH
• amiodaron * farmakologie   terapeutické užití   MeSH
• antibakteriální látky MeSH
• antivirové látky farmakologie   terapeutické užití   MeSH
• COVID-19 * MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amiodaron * MeSH
• antibakteriální látky MeSH
• antivirové látky MeSH

In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.

• Klíčová slova
• COVID-19, Caffeine, Docking, Molecular dynamic simulations, Vitamin B,
• MeSH
• antivirové látky farmakologie   chemie   MeSH
• farmakoterapie COVID-19 * MeSH
• kofein farmakologie   MeSH
• lidé MeSH
• niacinamid MeSH
• pandemie MeSH
• pyridoxamin MeSH
• racionální návrh léčiv MeSH
• SARS-CoV-2 MeSH
• simulace molekulového dockingu MeSH
• thiamin metabolismus   MeSH
• vitaminy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• kofein MeSH
• niacinamid MeSH
• pyridoxamin MeSH
• thiamin MeSH
• vitaminy MeSH

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accountable for causing the coronavirus diseases 2019 (COVID-19), is already declared as a pandemic disease globally. Like previously reported SARS-CoV strain, the novel SARS-CoV-2 also initiates the viral pathogenesis via docking viral spike-protein with the membranal angiotensin-converting enzyme 2 (ACE2) - a receptor on variety of cells in the human body. Therefore, COVID-19 is broadly characterized as a disease that targets multiple organs, particularly causing acute complications via organ-specific pathogenesis accompanied by destruction of ACE2+ cells, including alveolus, cardiac microvasculature, endothelium, and glomerulus. Under such circumstances, the high expression of ACE2 in predisposing individuals associated with anomalous production of the renin-angiotensin system (RAS) may promote enhanced viral load in COVID-19, which comparatively triggers excessive apoptosis. Furthermore, multi-organ injuries were found linked to altered ACE2 expression and inequality between the ACE2/angiotensin-(1-7)/mitochondrial Ang system (MAS) and renin-angiotensin-system (RAS) in COVID-19 patients. However, the exact pathogenesis of multi-organ damage in COVID-19 is still obscure, but several perspectives have been postulated, involving altered ACE2 expression linked with direct/indirect damages by the virus-induced immune responses, such as cytokinin storm. Thus, insights into the invasion of a virus with respect to ACE2 expression site can be helpful to simulate or understand the possible complications in the targeted organ during viral infection. Hence, this review summarizes the multiple organs invasion by SARS CoV-2 linked with ACE2 expression and their consequences, which can be helpful in the management of the COVID-19 pathogenesis under life-threatening conditions.

• Klíčová slova
• Angiotensin-(1-7), COVID-19, Extrapulmonary manifestation, Multiorgan damage, Pneumonia, SARS-CoV-2,
• MeSH
• angiotensin konvertující enzym metabolismus   MeSH
• angiotensin-konvertující enzym 2 MeSH
• COVID-19 * MeSH
• lidé MeSH
• pandemie MeSH
• SARS-CoV-2 * patogenita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• ACE2 protein, human MeSH Prohlížeč
• angiotensin konvertující enzym MeSH
• angiotensin-konvertující enzym 2 MeSH

The first known case of Coronavirus disease 2019 (COVID-19) was identified in December 2019. It has spread worldwide, leading to an ongoing pandemic, imposed restrictions and costs to many countries. Predicting the number of new cases and deaths during this period can be a useful step in predicting the costs and facilities required in the future. The purpose of this study is to predict new cases and deaths rate one, three and seven-day ahead during the next 100 days. The motivation for predicting every n days (instead of just every day) is the investigation of the possibility of computational cost reduction and still achieving reasonable performance. Such a scenario may be encountered in real-time forecasting of time series. Six different deep learning methods are examined on the data adopted from the WHO website. Three methods are LSTM, Convolutional LSTM, and GRU. The bidirectional extension is then considered for each method to forecast the rate of new cases and new deaths in Australia and Iran countries. This study is novel as it carries out a comprehensive evaluation of the aforementioned three deep learning methods and their bidirectional extensions to perform prediction on COVID-19 new cases and new death rate time series. To the best of our knowledge, this is the first time that Bi-GRU and Bi-Conv-LSTM models are used for prediction on COVID-19 new cases and new deaths time series. The evaluation of the methods is presented in the form of graphs and Friedman statistical test. The results show that the bidirectional models have lower errors than other models. A several error evaluation metrics are presented to compare all models, and finally, the superiority of bidirectional methods is determined. This research could be useful for organisations working against COVID-19 and determining their long-term plans.

• Klíčová slova
• ANFIS, Adaptive Network-based Fuzzy Inference System, ANN, Artificial Neural Network, AU, Australia, Bi-Conv-LSTM, Bidirectional Convolutional Long Short Term Memory, Bi-GRU, Bidirectional Gated Recurrent Unit, Bi-LSTM, Bidirectional Long Short-Term Memory, Bidirectional, COVID-19 Prediction, COVID-19, Coronavirus Disease 2019, Conv-LSTM, Convolutional Long Short Term Memory, Convolutional Long Short Term Memory (Conv-LSTM), DL, Deep Learning, DLSTM, Delayed Long Short-Term Memory, Deep learning, EMRO, Eastern Mediterranean Regional Office, ES, Exponential Smoothing, EV, Explained Variance, GRU, Gated Recurrent Unit, Gated Recurrent Unit (GRU), IR, Iran, LR, Linear Regression, LSTM, Long Short-Term Memory, Lasso, Least Absolute Shrinkage and Selection Operator, Long Short Term Memory (LSTM), MAE, Mean Absolute Error, MAPE, Mean Absolute Percentage Error, MERS, Middle East Respiratory Syndrome, ML, Machine Learning, MLP-ICA, Multi-layered Perceptron-Imperialist Competitive Calculation, MSE, Mean Square Error, MSLE, Mean Squared Log Error, Machine learning, New Cases of COVID-19, New Deaths of COVID-19, PRISMA, Preferred Reporting Items for Precise Surveys and Meta-Analyses, RMSE, Root Mean Square Error, RMSLE, Root Mean Squared Log Error, RNN, Repetitive Neural Network, ReLU, Rectified Linear Unit, SARS, Serious Intense Respiratory Disorder, SARS-COV, SARS coronavirus, SARS-COV-2, Serious Intense Respiratory Disorder Coronavirus 2, SVM, Support Vector Machine, VAE, Variational Auto Encoder, WHO, World Health Organization, WPRO, Western Pacific Regional Office,
• Publikační typ
• časopisecké články MeSH

Accumulating evidence suggests that obesity is a major risk factor for the initiation, progression, and outcomes of coronavirus disease 2019 (COVID-19). The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about the concomitant obesity and COVID-19 pandemics and their impact on health and society at large. In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity. Clearly, this has important implications for preventive measures, vaccination, and future therapeutic strategies to combat COVID-19. Furthermore, we will highlight important knowledge gaps and provide suggestions for future research and recommendations for policy actions. Since many new reports on COVID-19 rapidly appear, the present perspective should be seen as a focus for discussion to drive forward further understanding, research initiatives, and clinical management of COVID-19.

• Klíčová slova
• ACE2, COVID-19, Coronavirus disease 2019, Immune response, Obesity, Renin-angiotensin-aldosterone system, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2,
• MeSH
• angiotensin konvertující enzym MeSH
• Betacoronavirus imunologie   MeSH
• Coronavirus MeSH
• COVID-19 MeSH
• imunokompetence imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• koronavirové infekce imunologie   terapie   MeSH
• lidé MeSH
• náchylnost k nemoci MeSH
• obezita komplikace   imunologie   MeSH
• pandemie MeSH
• prognóza MeSH
• renin-angiotensin systém fyziologie   MeSH
• rizikové faktory MeSH
• SARS-CoV-2 MeSH
• virová pneumonie imunologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• angiotensin konvertující enzym MeSH

BACKGROUND: Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection. METHODS: Design: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT). PARTICIPANTS: Adult (> 18 years) within 24 h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥ 1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy. INTERVENTIONS: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg daily in two doses and azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. SECONDARY OUTCOMES: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90. DISCUSSION: Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival. TRIAL REGISTRATION: Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).

• Klíčová slova
• Azithromycin, COVID-19, Hydroxychloroquine, Novel coronavirus, Respiratory failure, SARS-CoV-2,
• MeSH
• azithromycin aplikace a dávkování   MeSH
• Betacoronavirus * MeSH
• COVID-19 MeSH
• dvojitá slepá metoda MeSH
• hydroxychlorochin aplikace a dávkování   MeSH
• jednotky intenzivní péče MeSH
• kombinovaná farmakoterapie MeSH
• koronavirové infekce farmakoterapie   mortalita   MeSH
• lidé MeSH
• pandemie MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma * MeSH
• SARS-CoV-2 MeSH
• virová pneumonie farmakoterapie   mortalita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• protokol klinické studie MeSH
• Názvy látek
• azithromycin MeSH
• hydroxychlorochin MeSH