High-Sensitivity High-Throughput Detection of Nucleic Acid Targets on Metasurface Fluorescence Biosensors.

Worldwide infection disease due to SARS-CoV-2 is tremendously affecting our daily lives. High-throughput detection methods for nucleic acids are emergently desired. Here, we show high-sensitivity and high-throughput metasurface fluorescence biosensors that are applicable for nucleic acid targets. The all-dielectric metasurface biosensors comprise silicon-on-insulator nanorod array and have prominent electromagnetic resonances enhancing fluorescence emission. For proof-of-concept experiment on the metasurface biosensors, we have conducted fluorescence detection of single-strand oligoDNAs, which model the partial sequences of SARS-CoV-2 RNA indicated by national infection institutes, and succeeded in the high-throughput detection at low concentrations on the order of 100 amol/mL without any amplification technique. As a direct detection method, the metasurface fluorescence biosensors exhibit high performance.

COVID-19: What you need to know.

The new SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) belongs to the family of coronaviruses, and it is a new strain of coronavirus that has not been previously identified in humans. It causes a contagious disease, which affects the respiratory system and can lead to severe complications in some cases. This virus was detected in China, then rapidly spread to almost all countries. Because of their complexity and the malignancy of the symptoms, they remain a center of interest for researchers. Herein, we provide a review in terms of transmission, clinical presentation, diagnosis, and treatment options in clinical trials of COVID-19 (coronavirus disease 2019), because readers need to update themselves regularly, and there is still much more to know about it.

COVID-19 Pandemic: A Serious Threat for Public Mental Health Globally.

Deep emotion traumas in societies around the globe are overcome by extreme human catastrophes such as natural disasters, social crises, war conflicts and infectious virus induced pandemic diseases, etc., can lead to enormous stress-related disorders. The current ongoing pandemic known as COVID-19 caused by novel Corona virus first appeared in Wuhan, city of China and then rapidly spread in the whole world. It has affected various frontiers of lives and caused numerous psychiatric problems like nervousness, post-traumatic stress disorder (PTSD), fear and uncertainty, panic attacks, depression, obsessive compulsory disorder, xenophobia and racism, etc. Globally COVID-19 has persuaded public mental health crisis. Furthermore, inadequate resources of public mental health services in several countries are discussed in this review, which will be further straighten by the upcoming increase in demand for mental health services due to the COVID-19 pandemic. All mental health sciences including Psychiatry can play a very important role in the comfort of COVID-19 infected individuals and their relatives, healthcare providers and society. We need to learn more about psychological and psychiatric features of COVID-19 from the perceptions of public and global mental health in order to cope up the present deteriorating situation caused by the SARS-CoV-2 pandemic.

SARS-CoV-2-associated Guillain-Barré syndrome is a para-infectious disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been linked to the Guillain-Barré syndrome (GBS). The objective of the present study is to identify specific clinical features of cases of GBS reported in the literature associated with SARS-CoV-2 infection. We searched Pubmed, and included single case reports and case series with full text in English, reporting original data of patients with GBS and a confirmed recent SARS-CoV-2 infection. Clinical data were extracted. We identified 28 articles (22 single case reports and 6 case series), reporting on a total of 44 GBS patients with confirmed SARS-CoV-2 infection. SARS-CoV-2 infection was confirmed through serum reverse transcriptase-polymerase chain reaction in 72.7% of cases. A total of 40 patients (91%) had symptoms compatible with SARS-CoV-2 infection before the onset of the GBS. The median period between the onset of symptoms of SARS-CoV-2 infection and symptoms of the GBS was 11.2 days (range, 2-23). The most common clinical features were: leg weakness (61.4%), leg paresthesia (50%), arm weakness (50.4%), arm paresthesia (50.4%), hyporeflexia/areflexia (48%) and ataxia (22.7%). In total, 38.6% (n = 17) were found to have facial paralysis. Among 37 patients in whom nerve-conduction studies and electromyography were performed, of which 26 patients (59.1%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the GBS. The present retrospective analysis support the role of the SARS-CoV-2 infection in the development of the GBS, may trigger GBS as para-infectious disease, and lead to SARS-CoV-2-associated GBS.

The Relevance of a Physical Active Lifestyle and Physical Fitness on Immune Defense: Mitigating Disease Burden, With Focus on COVID-19 Consequences.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a fast spreading virus leading to the development of Coronavirus Disease-2019 (COVID-19). Severe and critical cases are characterized by damage to the respiratory system, endothelial inflammation, and multiple organ failure triggered by an excessive production of proinflammatory cytokines, culminating in the high number of deaths all over the world. Sedentarism induces worse, continuous, and progressive consequences to health. On the other hand, physical activity provides benefits to health and improves low-grade systemic inflammation. The aim of this review is to elucidate the effects of physical activity in physical fitness, immune defense, and its contribution to mitigate the severe inflammatory response mediated by SARS-CoV-2. Physical exercise is an effective therapeutic strategy to mitigate the consequences of SARS-CoV-2 infection. In this sense, studies have shown that acute physical exercise induces the production of myokines that are secreted in tissues and into the bloodstream, supporting its systemic modulatory effect. Therefore, maintaining physical activity influence balance the immune system and increases immune vigilance, and also might promote potent effects against the consequences of infectious diseases and chronic diseases associated with the development of severe forms of COVID-19. Protocols to maintain exercise practice are suggested and have been strongly established, such as home-based exercise (HBE) and outdoor-based exercise (OBE). In this regard, HBE might help to reduce levels of physical inactivity, bed rest, and sitting time, impacting on adherence to physical activity, promoting all the benefits related to exercise, and attracting patients in different stages of treatment for COVID-19. In parallel, OBE must improve health, but also prevent and mitigate COVID-19 severe outcomes in all populations. In conclusion, HBE or OBE models can be a potent strategy to mitigate the progress of infection, and a coadjutant therapy for COVID-19 at all ages and different chronic conditions.

A geroscience perspective on immune resilience and infectious diseases: a potential case for metformin.

We are in the midst of the global pandemic. Though acute respiratory coronavirus (SARS-COV2) that leads to COVID-19 infects people of all ages, severe symptoms and mortality occur disproportionately in older adults. Geroscience interventions that target biological aging could decrease risk across multiple age-related diseases and improve outcomes in response to infectious disease. This offers hope for a new host-directed therapeutic approach that could (i) improve outcomes following exposure or shorten treatment regimens; (ii) reduce the chronic pathology associated with the infectious disease and subsequent comorbidity, frailty, and disability; and (iii) promote development of immunological memory that protects against relapse or improves response to vaccination. We review the possibility of this approach by examining available evidence in metformin: a generic drug with a proven safety record that will be used in a large-scale multicenter clinical trial. Though rigorous translational research and clinical trials are needed to test this empirically, metformin may improve host immune defenses and confer protection against long-term health consequences of infectious disease, age-related chronic diseases, and geriatric syndromes.

Non-communicable disease, sociodemographic factors, and risk of death from infection: a UK Biobank observational cohort study.

BACKGROUND: Non-communicable diseases (NCDs) have been highlighted as important risk factors for COVID-19 mortality. However, insufficient data exist on the wider context of infectious diseases in people with NCDs. We aimed to investigate the association between NCDs and the risk of death from any infection before the COVID-19 pandemic (up to Dec 31, 2019). METHODS: For this observational study, we used data from the UK Biobank observational cohort study to explore factors associated with infection death. We excluded participants if data were missing for comorbidities, body-mass index, smoking status, ethnicity, and socioeconomic deprivation, and if they were lost to follow-up or withdrew consent. Deaths were censored up to Dec 31, 2019. We used Poisson regression models including NCDs present at recruitment to the UK Biobank (obesity [defined by use of body-mass index] and self-reported hypertension, chronic heart disease, chronic respiratory disease, diabetes, cancer, chronic liver disease, chronic kidney disease, previous stroke or transient ischaemic attack, other neurological disease, psychiatric disorder, and chronic inflammatory and autoimmune rheumatological disease), age, sex, ethnicity, smoking status, and socioeconomic deprivation. Separate models were constructed with individual NCDs replaced by the total number of prevalent NCDs to define associations with multimorbidity. All analyses were repeated with non-infection-related death as an alternate outcome measure to establish differential associations of infection death and non-infection death. Associations are reported as incidence rate ratios (IRR) accompanied by 95% CIs. FINDINGS: After exclusion of 9210 (1·8%) of the 502 505 participants in the UK Biobank cohort, our study sample comprised 493 295 individuals. During 5 273 731 person-years of follow-up (median 10·9 years [IQR 10·1-11·6] per participant), 27 729 deaths occurred, of which 1385 (5%) were related to infection. Advancing age, male sex, smoking, socioeconomic deprivation, and all studied NCDs were independently associated with the rate of both infection death and non-infection death. Compared with White ethnicity, a pooled Black, Asian, and minority ethnicity group was associated with a reduced risk of infection death (IRR 0·64, 95% CI 0·46-0·87) and non-infection death (0·80, 0·75-0·86). Stronger associations with infection death than with non-infection death were observed for advancing age (age 65 years vs 45 years: 7·59, 95% CI 5·92-9·73, for infection death vs 5·21, 4·97-5·48, for non-infection death), current smoking (vs never smoking: 3·69, 3·19-4·26, vs 2·52, 2·44-2·61), socioeconomic deprivation (most vs least deprived quintile: 2·13, 1·78-2·56, vs 1·38, 1·33-1·43), class 3 obesity (vs non-obese: 2·21, 1·74-2·82, vs 1·55, 1·44-1·66), hypertension (1·36, 1·22-1·53, vs 1·15, 1·12-1·18), respiratory disease (2·21, 1·96-2·50, vs 1·28, 1·24-1·32), chronic kidney disease (5·04, 4·28-7·31, vs 2·50, 2·20-2·84), psychiatric disease (1·56, 1·30-1·86, vs 1·23, 1·18-1·29), and chronic inflammatory and autoimmune rheumatological disease (2·45, 1·99-3·02, vs 1·41, 1·32-1·51). Accrual of multimorbidity was also more strongly associated with risk of infection death (five or more comorbidities vs none: 9·53, 6·97-13·03) than of non-infection death (5·26, 4·84-5·72). INTERPRETATION: Several NCDs are associated with an increased risk of infection death, suggesting that some of the reported associations with COVID-19 mortality might be non-specific. Only a subset of NCDs, together with the accrual of multimorbidity, advancing age, smoking, and socioeconomic deprivation, were associated with a greater IRR for infection death than for other causes of death. Further research is needed to define why these risk factors are more strongly associated with infection death, so that more effective preventive strategies can be targeted to high-risk groups. FUNDING: British Heart Foundation.

The neurological sequelae of pandemics and epidemics.

Neurological manifestations in pandemics frequently cause short and long-term consequences which are frequently overlooked. Despite advances in the treatment of infectious diseases, nervous system involvement remains a challenge, with limited treatments often available. The under-recognition of neurological manifestations may lead to an increase in the burden of acute disease as well as secondary complications with long-term consequences. Nervous system infection or dysfunction during pandemics is common and its enduring consequences, especially among vulnerable populations, are frequently forgotten. An improved understanding the possible mechanisms of neurological damage during epidemics, and increased recognition of the possible manifestations is fundamental to bring insights when dealing with future outbreaks. To reverse this gap in knowledge, we reviewed all the pandemics, large and important epidemics of human history in which neurological manifestations are evident, and described the possible physiological processes that leads to the adverse sequelae caused or triggered by those pathogens.

Novel Chest Radiographic Biomarkers for COVID-19 Using Radiomic Features Associated with Diagnostics and Outcomes.

COVID-19 is a highly contagious disease that can cause severe pneumonia. Patients with pneumonia undergo chest X-rays (XR) to assess infiltrates that identify the infection. However, the radiographic characteristics of COVID-19 are similar to the other acute respiratory syndromes, hindering the imaging diagnosis. In this work, we proposed identifying quantitative/radiomic biomarkers for COVID-19 to support XR assessment of acute respiratory diseases. This retrospective study used different cohorts of 227 patients diagnosed with pneumonia; 49 of them had COVID-19. Automatically segmented images were characterized by 558 quantitative features, including gray-level histogram and matrices of co-occurrence, run-length, size zone, dependence, and neighboring gray-tone difference. Higher-order features were also calculated after applying square and wavelet transforms. Mann-Whitney U test assessed the diagnostic performance of the features, and the log-rank test assessed the prognostic value to predict Kaplan-Meier curves of overall and deterioration-free survival. Statistical analysis identified 51 independently validated radiomic features associated with COVID-19. Most of them were wavelet-transformed features; the highest performance was the small dependence matrix feature of "low gray-level emphasis" (area under the curve of 0.87, sensitivity of 0.85, [Formula: see text]). Six features presented short-term prognostic value to predict overall and deterioration-free survival. The features of histogram "mean absolute deviation" and size zone matrix "non-uniformity" yielded the highest differences on Kaplan-Meier curves with a hazard ratio of 3.20 ([Formula: see text]). The radiomic markers showed potential as quantitative measures correlated with the etiologic agent of acute infectious diseases and to stratify short-term risk of COVID-19 patients.

Bacterial Membrane Vesicles in Pneumonia: From Mediators of Virulence to Innovative Vaccine Candidates.

Pneumonia due to respiratory infection with most prominently bacteria, but also viruses, fungi, or parasites is the leading cause of death worldwide among all infectious disease in both adults and infants. The introduction of modern antibiotic treatment regimens and vaccine strategies has helped to lower the burden of bacterial pneumonia, yet due to the unavailability or refusal of vaccines and antimicrobials in parts of the global population, the rise of multidrug resistant pathogens, and high fatality rates even in patients treated with appropriate antibiotics pneumonia remains a global threat. As such, a better understanding of pathogen virulence on the one, and the development of innovative vaccine strategies on the other hand are once again in dire need in the perennial fight of men against microbes. Recent data show that the secretome of bacteria consists not only of soluble mediators of virulence but also to a significant proportion of extracellular vesicles-lipid bilayer-delimited particles that form integral mediators of intercellular communication. Extracellular vesicles are released from cells of all kinds of organisms, including both Gram-negative and Gram-positive bacteria in which case they are commonly termed outer membrane vesicles (OMVs) and membrane vesicles (MVs), respectively. (O)MVs can trigger inflammatory responses to specific pathogens including S. pneumonia, P. aeruginosa, and L. pneumophila and as such, mediate bacterial virulence in pneumonia by challenging the host respiratory epithelium and cellular and humoral immunity. In parallel, however, (O)MVs have recently emerged as auspicious vaccine candidates due to their natural antigenicity and favorable biochemical properties. First studies highlight the efficacy of such vaccines in animal models exposed to (O)MVs from B. pertussis, S. pneumoniae, A. baumannii, and K. pneumoniae. An advanced and balanced recognition of both the detrimental effects of (O)MVs and their immunogenic potential could pave the way to novel treatment strategies in pneumonia and effective preventive approaches.

Advances in developing small molecule SARS 3CLpro inhibitors as potential remedy for corona virus infection.

Originated in China, coronavirus disease 2019 (COVID-19)- the highly contagious and fatal respiratory disease caused by SARS-CoV-2 has already infected more than 29 million people worldwide with a mortality rate of 3.15% (according to World Health Organization's (WHO's) report, September 2020) and the number is exponentially increasing with no remedy whatsoever discovered till date. But it is not the first time this infectious viral disease has appeared, in 2002 SARS-CoV infected more than 8000 individuals of which 9.6% patients died and in 2012 approximately 35% of MERS-CoV infected patients have died. Literature reports indicate that a chymotripsin-like cystein protease (3CLpro) is responsible for the replication of the virus inside the host cell. Therefore, design and synthesis of 3CLpro inhibitor molecules play a great impact in drug development against this COVID-19 pandemic. In this review, we are discussing the anti-SARS effect of some small molecule 3CLpro inhibitors with their various binding modes of interactions to the target protein.

Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.

Tuberculosis (TB) is still the number one cause of death due to an infectious disease. Pharmacokinetics and pharmacodynamics of anti-TB drugs are key in the optimization of TB treatment and help to prevent slow response to treatment, acquired drug resistance, and adverse drug effects. The aim of this review was to provide an update on the pharmacokinetics and pharmacodynamics of anti-TB drugs and to show how population pharmacokinetics and Bayesian dose adjustment can be used to optimize treatment. We cover aspects on preclinical, clinical, and population pharmacokinetics of different drugs used for drug-susceptible TB and multidrug-resistant TB. Moreover, we include available data to support therapeutic drug monitoring of these drugs and known pharmacokinetic and pharmacodynamic targets that can be used for optimization of therapy. We have identified a wide range of population pharmacokinetic models for first- and second-line drugs used for TB, which included models built on NONMEM, Pmetrics, ADAPT, MWPharm, Monolix, Phoenix, and NPEM2 software. The first population models were built for isoniazid and rifampicin; however, in recent years, more data have emerged for both new anti-TB drugs, but also for defining targets of older anti-TB drugs. Since the introduction of therapeutic drug monitoring for TB over 3 decades ago, further development of therapeutic drug monitoring in TB next steps will again depend on academic and clinical initiatives. We recommend close collaboration between researchers and the World Health Organization to provide important guideline updates regarding therapeutic drug monitoring and pharmacokinetics/pharmacodynamics.

SARS-CoV-2 seroconversions and chains of infection in healthcare professionals in a German maximum care provider (The CoSHeP study).

INTRODUCTION: The CoSHeP study provides novel data on SARS-CoV-2 seroconversion rates in healthcare professionals (HP) at risk at the University Hospital Bonn, a maximum healthcare provider in a region of 900.000 inhabitants. METHODS: Single-center, longitudinal observational study investigating rate of SARS-CoV-2 IgG seroconversion in HP at 2 time-points. SARS-CoV-2 IgG was measured with Roche Elecsys Anti-SARS-CoV-2 assay. RESULTS: Overall, 150 HP were included. Median age was 35 (range: 19-68). Main operational areas were intensive care unit (53%, n = 80), emergency room (31%, n = 46), and infectious disease department (16%, n = 24). SARS-CoV-2-IgG was detected in 5 participants (3%) at inclusion in May/June 2020, and in another 11 participants at follow-up (December 2020/ January 2021). Of the 16 seropositive participants, 14 had already known their SARS-CoV-2 infection because they had performed a PCR-test previously triggered by symptoms. Trailing chains of infection by self-assessment, 31% (n = 5) of infections were acquired through private contacts, 25% (n = 4) most likely through semi-private contacts during work. 13% (n = 2) were assumed to result through contact with contagious patients, further trailing was unsuccessful in 31% (n = 5). All five participants positive for SARS-CoV-2 IgG at inclusion remained positive with a median of 7 months after infection. DISCUSSION: Frontline HP caring for hospitalized patients with COVID-19 are at higher risk of SARS-CoV-2 infections. Noteworthy, based upon identified chains of infection most of the infections were acquired in private environment and semi-private contacts during work. The low rate of infection through infectious patients reveals that professional hygiene standards are effective in preventing SARS-CoV-2 infections in HP. Persisting SARS-CoV-2-IgG might indicate longer lasting immunity supporting prioritization of negative HP for vaccination.

SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus.

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of Coronavirus Disease-2019 (COVID-19), a respiratory disease, has infected almost one hundred million people since the end of 2019, killed over two million, and caused worldwide social and economic disruption. Because the mechanisms of SARS-CoV-2 infection of host cells and its pathogenesis remain largely unclear, there are currently no antiviral drugs with proven efficacy. Besides severe respiratory and systematic symptoms, several comorbidities increase risk of fatal disease outcome. Therefore, it is required to investigate the impacts of COVID-19 on pre-existing diseases of patients, such as cancer and other infectious diseases. In the current study, we report that SARS-CoV-2 encoded proteins and some currently used anti-COVID-19 drugs are able to induce lytic reactivation of Kaposi's sarcoma-associated herpesvirus (KSHV), one of major human oncogenic viruses, through manipulation of intracellular signaling pathways. Our data indicate that those KSHV + patients especially in endemic areas exposure to COVID-19 or undergoing the treatment may have increased risks to develop virus-associated cancers, even after they have fully recovered from COVID-19.

Acute Respiratory Distress Syndrome due to Mycoplasma pneumoniae Misinterpreted as SARS-CoV-2 Infection.

BACKGROUND: In 2020, a novel coronavirus caused a global pandemic with a clinical picture termed COVID-19, accounting for numerous cases of ARDS. However, there are still other infectious causes of ARDS that should be considered, especially as the majority of these pathogens are specifically treatable. Case Presentation. We present the case of a 36-year-old gentleman who was admitted to the hospital with flu-like symptoms, after completing a half-marathon one week before admission. As infection with SARS-CoV-2 was suspected based on radiologic imaging, the hypoxemic patient was immediately transferred to the ICU, where he developed ARDS. Empiric antimicrobial chemotherapy was initiated, the patient deteriorated further, therapy was changed, and the patient was transferred to a tertiary care ARDS center. As cold agglutinins were present, the hypothesis of an infection with SARS-CoV-2 was then questioned. Bronchoscopic sampling revealed Mycoplasma (M.) pneumoniae. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. CONCLUSION: Usually, M. pneumoniae causes mild disease. When antimicrobial chemotherapy was adjusted, the patient recovered quickly. The case underlines the importance to adhere to established treatment guidelines, scrutinize treatment modalities, and not to forget other potential causes of severe pneumonia or ARDS.

COVID-index: A texture-based approach to classifying lung lesions based on CT images.

COVID-19 is an infectious disease caused by a newly discovered type of coronavirus called SARS-CoV-2. Since the discovery of this disease in late 2019, COVID-19 has become a worldwide concern, mainly due to its high degree of contagion. As of April 2021, the number of confirmed cases of COVID-19 reported to the World Health Organization has already exceeded 135 million worldwide, while the number of deaths exceeds 2.9 million. Due to the impacts of the disease, efforts in the literature have intensified in terms of studying approaches aiming to detect COVID-19, with a focus on supporting and facilitating the process of disease diagnosis. This work proposes the application of texture descriptors based on phylogenetic relationships between species to characterize segmented CT volumes, and the subsequent classification of regions into COVID-19, solid lesion or healthy tissue. To evaluate our method, we use images from three different datasets. The results are promising, with an accuracy of 99.93%, a recall of 99.93%, a precision of 99.93%, an F1-score of 99.93%, and an AUC of 0.997. We present a robust, simple, and efficient method that can be easily applied to 2D and/or 3D images without limitations on their dimensionality.

Changes in infection-related hospitalizations in children following pandemic restrictions: an interrupted time-series analysis of total population data.

BACKGROUND: Infectious diseases are a leading cause of hospitalization during childhood. The various mitigation strategies implemented to control the coronavirus disease (COVID-19) pandemic could have additional, unintended benefits for limiting the spread of other infectious diseases and their associated burden on the health care system. METHODS: We conducted an interrupted time-series analysis using population-wide hospitalization data for the state of Victoria, Australia. Infection-related hospitalizations for children and adolescents (aged <18 years, total source population ∼1.4 million) were extracted using pre-defined International Classification of Diseases 10th Revision Australian Modification (ICD-10-AM) codes. The change in weekly hospitalization rates (incidence rate ratio, IRR) for all infections following the introduction of pandemic-related restrictions from 15 March 2020 was estimated. RESULTS: Over 2015-19, the mean annual incidence of hospitalization with infection among children less than 18 years was 37 per 1000 population. There was an estimated 65% (95% CI 62-67%) reduction in the incidence of overall infection-related hospitalizations associated with the introduction of pandemic restrictions. The reduction was most marked in younger children (at least 66% in those less than 5 years of age) and for lower respiratory tract infections (relative reduction 85%, 95% CI 85-86%). CONCLUSIONS: The wider impacts of pandemic mitigation strategies on non-COVID-19 infection-related hospitalizations are poorly understood. We observed marked and rapid decreases in hospitalized childhood infection. In tandem with broader consequences, sustainable measures, such as improved hand hygiene, could reduce the burden of severe childhood infection post-pandemic and the social and economic costs of hospitalization.

Existing Drugs Considered as Promising in COVID-19 Therapy.

COVID-19 is a respiratory disease caused by newly discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease at first was identified in the city of Wuhan, China in December 2019. Being a human infectious disease, it causes high fever, cough, breathing problems. In some cases it can be fatal, especially in people with comorbidities like heart or kidney problems and diabetes. The current COVID-19 treatment is based on symptomatic therapy, so finding an appropriate drug against COVID-19 remains an immediate and crucial target for the global scientific community. Two main processes are thought to be responsible for the COVID-19 pathogenesis. In the early stages of infection, disease is determined mainly by virus replication. In the later stages of infection, by an excessive immune/inflammatory response, leading to tissue damage. Therefore, the main treatment options are antiviral and immunomodulatory/anti-inflammatory agents. Many clinical trials have been conducted concerning the use of various drugs in COVID-19 therapy, and many are still ongoing. The majority of trials examine drug reposition (repurposing), which seems to be a good and effective option. Many drugs have been repurposed in COVID-19 therapy including remdesivir, favipiravir, tocilizumab and baricitinib. The aim of this review is to highlight (based on existing and accessible clinical evidence on ongoing trials) the current and available promising drugs for COVID-19 and outline their characteristics.

Mediastinal lymphadenopathy in COVID-19: A review of literature.

A novel coronavirus disease 2019 (COVID-19) is a progressive viral disease that affected people around the world with widespread morbidity and mortality. Patients with COVID-19 infection typically had pulmonary manifestation but can also present with gastrointestinal, cardiac, or neurological system dysfunction. Chest imaging in patients with COVID-19 commonly show bilateral lung involvement with bilateral ground-glass opacity and consolidation. Mediastinal lymphadenopathy can be found due to infectious or non-infectious etiologies. It is commonly found to be associated with malignant diseases, sarcoidosis, and heart failure. Mediastinal lymph node enlargement is not a typical computer tomography of the chest finding of patients with COVID-19 infection. We summarized the literature which suggested or investigated the mediastinal lymph node enlargement in patients with COVID-19 infection. Further studies are needed to better characterize the importance of mediastinal lymphadenopathy in patients with COVID-19 infection.

Understanding the pathophysiological changes via untargeted metabolomics in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disease caused by a new strain of the coronavirus. There is limited data on the pathogenesis and the cellular responses of COVID-19. In this study, we aimed to determine the variation of metabolites between healthy control and COVID-19 via the untargeted metabolomics method. Serum samples were obtained from 44 COVID-19 patients and 41 healthy controls. Untargeted metabolomics analyses were performed by the LC/Q-TOF/MS (liquid chromatography quadrupole time-of-flight mass spectrometry) method. Data acquisition, classification, and identification were achieved by the METLIN database and XCMS. Significant differences were determined between patients and healthy controls in terms of purine, glutamine, leukotriene D4 (LTD4), and glutathione metabolisms. Downregulations were determined in R-S lactoglutathione and glutamine. Upregulations were detected in hypoxanthine, inosine, and LTD4. Identified metabolites indicate roles for purine, glutamine, LTD4, and glutathione metabolisms in the pathogenesis of the COVID-19. The use of selective leukotriene D4 receptor antagonists, targeting purinergic signaling as a therapeutic approach and glutamine supplementation may decrease the severity and mortality of COVID-19.