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Ethnopharmacological relevance Worldwide, one of the drivers of substitution and adulteration is the cost of the natural resources (plants, animals, fungi) that are ingredients of traditional medicines. Relatively few studies have been done that link prices of traditional medicine ingredients to what drives changes in price, yet this is an important topic. Theoretically, prices have been widely considered as an economic indicator of resource scarcity. Rare, slow growing medicinal plants sell for high prices and common, less popular species for low prices. Price levels also influence the viability of farming vs. wild harvest (and incentives to overharvest high value species when tenure is weak). Prices can also influence the harvesting or buying behaviour of harvesters, traders or manufacturers. When prices are high, then there is a greater incentive to use cheaper substitute species or adulterants. As previous studies on herbal medicine ingredients have shown, adulteration applies in a wide variety of cases, including to some Traditional Chinese Medicine (TCM) species. Aim of the study The aim of this study was to gain a better understanding of which factors influenced changes in the market prices of document prices for four popular, but very different traditional Chinese medicine (TCM) species (2002 – 2017). Materials and methods Fluctuations in market prices were followed over a 15-year period (2002–2017) for four very different TCM ingredients: two plant species (one wild harvested for fruits (Schisandra sphenanthera Rehder & E.H. Wilson) the other in a transition from wild harvest to cultivation (Paris polyphylla Smith), an animal species (the Tokay gecko (Gekko gecko L.)) and the entomophagous “caterpillar fungus” (Ophiocordyceps sinensis (Berk). G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora). Results High prices of medicinal plants are widely considered to reflect resource scarcity. Real-time market prices for three of the four very different TCM species we studied all showed major price fluctuations. The exception was P. polyphylla, whose wild populations are widely known to be increasingly scarce, where there was a steady increase in price, with few fluctuations in the upward price trend. The three other species showed significant price fluctuations. These were driven by multiple factors. Ecological and biogeographic factors that influence abundance or scarcity of supply certainly played a role. But other factors were also influential. These included both national and global economic factors (the influence of the Global Financial Crisis (GFC)), national policy changes that in turn influenced businessmen giving expensive gifts (that included O. sinensis)), climate change (influencing fruiting success of S. sphenanthera), price speculation by traders and lack of information (e.g: reduction in G. gecko prices due to traders incorrectly believing that domestication would increase supplies). Conclusions Price fluctuations in the four TCM species we examined are influenced by many factors and not just resource scarcity. And the situation is more complex than the trajectory based on Homma's (1992) model, where he predicted that higher prices would result in a shift to cultivation, thus replacing wild harvest. In case of both O. sinensis and P. polyphylla, Homma (1992, 1996) was right in terms of scarcity and high prices stimulating a major investment in cultivation (P. polyphylla) and artificial production (O. sinensis). But in both cases, intensive production through cultivation or artificial propagation do not yet occur on a large enough scale to reduce harvest of wild stocks. Substitution and adulteration occur with all four species. Improving information to medicinal plant traders on the supply status of TCM stocks, whether from wild harvest or from cultivation could benefit product quality, cultivation initiatives and conservation efforts., Graphical abstract fx1

The emergence and reemergence of coronavirus epidemics sparked renewed concerns from global epidemiology researchers and public health administrators. Mathematical models that represented how contact tracing and follow-up may control Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) transmissions were developed for evaluating different infection control interventions, estimating likely number of infections as well as facilitating understanding of their likely epidemiology. We reviewed mathematical models for contact tracing and follow-up control measures of SARS and MERS transmission. Model characteristics, epidemiological parameters and intervention parameters used in the mathematical models from seven studies were summarized. A major concern identified in future epidemics is whether public health administrators can collect all the required data for building epidemiological models in a short period of time during the early phase of an outbreak. Also, currently available models do not explicitly model constrained resources. We urge for closed-loop communication between public health administrators and modelling researchers to come up with guidelines to delineate the collection of the required data in the midst of an outbreak and the inclusion of additional logistical details in future similar models. Keywords: Contact Tracing, Coronavirus Epidemics, Transmission Modelling, SARS, MERS

Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at significantly lower concentrations than the plasma trough levels achieved by the dosage adopted for influenza treatment and exhibits efficacy against coronavirus disease 2019 (COVID-19) pneumonia. Although high doses of favipiravir are required due to the molecule being a purine analog, its conversion into the active form in infected cells with active viral RNA synthesis enhances the antiviral specificity and selectivity as a chain terminator with lethal mutagenesis. Another characteristic feature is the lack of generation of favipiravir-resistant virus. COVID-19 pneumonia is caused by strong cell-mediated immunity against virus-infected cells, and the inflammatory response induced by adaptive immunity continues to peak for 3 to 5 days despite antiviral treatment. This has also been observed in herpes zoster (HZ) and cytomegalovirus (CMV) pneumonia. Inflammation due to an immune response may mask the effectiveness of favipiravir against COVID-19 pneumonia. Favipiravir significantly shortened the recovery time in patients with mild COVID-19 pneumonia by 3 days with the start of treatment by the 5th day of symptom onset. Since both CMV and COVID-19 pneumonia are caused by adaptive immunity and prevention of cytomegalovirus pneumonia is the standard treatment due to difficulties in treating refractory CMV pneumonia, COVID-19 pneumonia should be prevented with early treatment as well. In the present study, we have comprehensively reviewed the optimal antiviral therapy for COVID-19 based on clinical trials of favipiravir for the treatment of COVID-19 pneumonia and the concurrently established therapies for other viral infections, particularly HZ and CMV pneumonia. Optimally, antivirals should be administered immediately after COVID-19 diagnosis, similar to that after influenza diagnosis, to prevent COVID-19 pneumonia and complications resulting from microangiopathy.

Setting up treatment strategies is the highest concern today to reduce the fatality of COVID-19. Due to a very new kind of virus attack, no specific treatment has been discovered to date. The most crucial way to dominate the disease severity is now the repurposing of drugs. In this review, we focused on the current treatment approaches targeting the crucial causative factors for the disease burden through cytokine storm or cytokine release syndrome. Several vaccines have been developed and have been applied already for prevention purposes, and several are on the way to be developed, although the effects and side effects are under observation. Presently, regulation of the immune response through intervention treatment methods has been adjusted on the basis of the COVID-19 severity stage and generally includes vaccines, immunotherapies including convalescent plasma and immunoglobulin treatment, monoclonal antibodies, cytokine therapy, complement inhibition, regenerative medicine, and repurposed anti-inflammatory and immune-regulatory drugs. Combination therapy is not acceptable in all respects because there is no concrete evidence in clinical trials or in vivo data. Target-specific drug therapies, such as inhibition of cytokine-producing signaling pathways, could be an excellent solution and thus reduce the severity of inflammation and disease severity. Therefore, gathering information about the mechanism of disease progression, possible goals, and drug efficacy of immune-based approaches to combat COVID-19 in the context of orderly review analysis is consequential.

BACKGROUND: The prothrombotic phenotype and diffuse intravascular coagulation observed in COVID-19 reflect endothelial dysfunction, which is linked to blood flow delivery deficiencies and cardiovascular risk. Assessments of detect vascular deficiencies among newly diagnosed and hospitalized patients due to COVID-19 have yet to be determined. OBJECTIVE: To assess endothelial function characteristics in relation to length of hospitalization and mortality in patients diagnosed with COVID-19 and compare to patients without COVID-19. METHODS: A prospective observational study involving 180 patients with confirmed COVID-19 (COVID-19 group) or suspected and ruled out COVID-19 (Non-COVID-19 group). Clinical evaluation and flow mediated vasodilation (FMD) were performed between the first 24-48 h of hospitalization. Patients were followed until death or discharge. RESULTS: We evaluated 98 patients (COVID-19 group) and 82 (Non-COVID-19 group), COVID-19 group remained hospitalized longer and more deaths occurred compared to the Non-COVID-19 group (p = 0.01; and p

The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis.

A phage library displaying 1010 variants of the fibronectin type III (FN3) domain was affinity selected with the biotinylated form of the receptor binding domain (RBD, residues 319-541) of the SARS-CoV-2 virus spike protein. Nine binding FN3 variants (i.e. monobodies) were recovered, representing four different primary structures. Soluble forms of the monobodies bound to several different preparations of the RBD and the S1 spike subunit, with affinities ranging from 3 to 14 nM as measured by bio-layer interferometry. Three of the four monobodies bound selectively to the RBD of SARS-CoV-2, with the fourth monobody showing slight cross-reactivity to the RBD of SARS-CoV-1 virus. Examination of binding to the spike fragments and its trimeric form revealed that the monobodies recognise at least three overlapping epitopes on the RBD of SARS-CoV-2. While pairwise tests failed to identify a monobody pair that could bind simultaneously to the RBD, one monobody could simultaneously bind to the RBD with the ectodomain of the cellular receptor angiotensin converting enzyme 2 (ACE2). All four monobodies successfully bound the RBD after overexpression in Chinese hamster ovary (CHO) cells as fusions to the Fc domain of human IgG1.

Highlights • SARS-CoV-2 can infect multiple organs leading to their dysfunction, so a pleiotropic therapy would be advantageous. • MSC: MSC can simultaneously address injuries in multiple organs and promote their repair. • MSC, immunomodulators by excellence, may counteract infection and cytokine storm in COVID-19 patients. • MSC therapy is being tested in clinical trials for COVID-19 patients and proved to be safe and effective so far. • More clinical studies, addressing MSC use for COVID-19, with bigger cohorts and suitable controls are welcome., The devastating global impact of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has prompted scientists to develop novel strategies to fight Coronavirus Disease of 2019 (COVID-19), including the examination of pre-existing treatments for other viral infections in COVID-19 patients. This review provides a reasoned discussion of the possible use of Mesenchymal Stromal Cells (MSC) or their products as a treatment in SARS-CoV-2-infected patients. The main benefits and concerns of using this cellular therapy, guided by preclinical and clinical data obtained from similar pathologies will be reviewed. MSC represent a highly immunomodulatory cell population and their use may be safe according to clinical studies developed in other pathologies. Notably, four clinical trials and four case reports that have already been performed in COVID-19 patients obtained promising results. The clinical application of MSC in COVID-19 is very preliminary and further investigational studies are required to determine the efficacy of the MSC therapy. Nevertheless, these preliminary studies were important to understand the therapeutic potential of MSC in COVID-19. Based on these encouraging results, the United States Food and Drug Administration (FDA) authorized the compassionate use of MSC, but only in patients with Acute Respiratory Distress Syndrome (ARDS) and a poor prognosis. In fact, patients with severe SARS-CoV-2 can present infection and tissue damage in different organs, such as lung, heart, liver, kidney, gut and brain, affecting their function. MSC may have pleiotropic activities in COVID-19, with the capacity to fight inflammation and repair lesions in several organs.

The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19).A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 μg/L vs. 501.90 μg/L,The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19).Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROCLa cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 μg/L vs. 501,90 μg/L, El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

Graphical abstract, Highlights • A year since the first report of the SARS-CoV-2, over 57 million cases have been diagnosed, and over 1.37 million have died worldwide. • An uncontrolled inflammatory response linked to a cytokine storm has been associated with pulmonary inflammation severity. • The genetic drifting of SARS-CoV-2 has been extremely slow, increasing the prospect of designing vaccines against all viral clades. • None of the therapeutic approaches currently used appears to be decisive for the treatment of COVID-19. • Three vaccines have demonstrated efficacy superior to 90%. Two of these vaccines, BNT162b2 and mRNA-1273, were based on an RNA platform, while Sputnik V was based on a non-replicating viral vector platform., Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) results in diverse outcomes. The symptoms appear to be more severe in males older than 65 and people with underlying health conditions; approximately one in five individuals could be at risk worldwide. The virus’s sequence was rapidly established days after the first cases were reported and identified an RNA virus from the Coronaviridae family closely related to a Betacoronavirus virus found in bats in China. SARS-CoV-2 is the seventh coronavirus known to infect humans, and with the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), the only ones to cause severe diseases. Lessons from these two previous outbreaks guided the identification of critical therapeutic targets such as the spike viral proteins promoting the virus’s cellular entry through the angiotensin-converting enzyme 2 (ACE2) receptor expressed on the surface of multiple types of eukaryotic cells. Although several therapeutic agents are currently evaluated, none seems to provide a clear path for a cure. Also, various types of vaccines are developed in record time to address the urgency of efficient SARS-CoV-2 prevention. Currently, 58 vaccines are evaluated in clinical trials, including 11 in phase III, and 3 of them reported efficacy above 90%. The results so far from the clinical trials suggest the availability of multiple effective vaccines within months.

The coronavirus disease 2019 (COVID-19) has now rapidly spread around the world, causing an outbreak of acute infectious pneumonia. To develop effective and safe therapies for the prevention and treatment of COVID-19 has become the major global public health concern. Traditional medicine (TM)/herbal medicines (HMs) have been used to treat multiple epidemics in human history, which brings hope for the fight against COVID-19 in some areas. For example, in China, India, and South Korea with traditional medication history and theory, the governments issued a series of guidelines to support TM/HMs in the medication of COVID-19. In contrast, other countries e.g. North American and European governments are typically silent on these practices, unless to warn of possible harm and overselling. Such difference is due to the discrepancy in culture, history and philosophical views of health care and medication, as well as unharmonized policies and standards in the regulation and legalization of TM/HMs among different areas. Herein, we reviewed the responses and scientific researches from seven selected countries on the policies and legalization of TM/HMs to treat COVID-19, and also analyzed the major challenges and concerns to utilize the traditional knowledge and resource., Graphical Abstract ga1

Introduction: Early in the epidemic of corona virus disease 2019, the Chinese government recruited a proportion of healthcare workers to support the designated hospital (Huoshenshan Hospital) in Wuhan, China. The majority of front-line medical staff suffered from adverse effects, but their real health status during COVID-19 epidemic was still unknown. The aim of the study was to explore the latent relationship of the physical and mental health of front-line medical staff during this special period. Methods: A total of 115 military medical staff were recruited between February 17th and February 29th, 2020 and asked to complete questionnaires assessing socio-demographic and clinical characteristics, self-reported sleep status, fatigue, resilience and anxiety. Results: 55 medical staff worked within Intensive Care and 60 worked in Non-intensive Care, the two groups were significantly different in general fatigue, physical fatigue and tenacity (P

International audience; With continued expansion of the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), both antiviral drugs as well as effective vaccines are desperately needed to treat patients at high risk of life-threatening disease. Here, we present in vitro evidence for significant inhibition of SARS-CoV-2 by oleandrin and a defined extract of N. oleander (designated as PBI-06150). Using Vero cells, we found that prophylactic (pre-infection) oleandrin (as either the pure compound or as the active principal ingredient in PBI-06150) administration at concentrations as low as 0.05g/ml exhibited potent antiviral activity against SARS-CoV-2, with an 800-fold reduction in virus production, and a 0.1g/ml concentration resulted in a greater than 3000-fold reduction in infectious virus production. The half maximal effective concentration (EC50) values were 11.98ng/ml when virus output was measured at 24h post-infection, and 7.07ng/ml measured at 48h post-infection. Therapeutic (post-infection) treatment up to 24h after SARS-CoV-2 infection of Vero cells also reduced viral titers, with 0.1g/ml and 0.05g/ml concentrations causing greater than 100-fold reduction as measured at 48h, and the 0.05g/ml concentration resulting in a 78-fold reduction. Concentrations of oleandrin up to 10g/ml were well tolerated in Vero cells. We also present in vivo evidence of the safety and efficacy of defined N. oleander extract (PBI-06150), which was administered to golden Syrian hamsters in a preparation containing as high as 130g/ml of oleandrin. In comparison to administration of control vehicle, PBI-06150 provided a statistically significant reduction of the viral titer in the nasal turbinates (nasal conchae). The potent prophylactic and therapeutic antiviral activities demonstrated here, together with initial evidence of its safety and efficacy in a relevant hamster model of COVID-19, support the further development of oleandrin and/or defined extracts containing this molecule for the treatment of SARS-CoV-2 and associated COVID-19 disease and potentially also for reduction of virus spread by persons diagnosed early after infection.

Highlights • Screening more than fifty natural products for the SARS CoV-2 Mpro protein target • The compounds with higher hydrophobicity and lower flexibility can be more favorable inhibitor • Terpenoid from marine sponge Cacospongia mycofijiensis shows excellent SARS CoV-2 Mpro inhibitory activity • In the point of binding affinity, bioavailability, pharmacokinetics and toxicity, the natural product can act as a potential drug candidate against COVID-19 virus., Traditional medicines contain natural products (NPs) as main ingredient which always give new direction and paths to develop new advanced medicines. In the COVID-19 pandemic, NPs can be used or can help to find new compound against it. The SARS coronavirus-2 main protease (SARS CoV-2 Mpro) enzyme, arbitrate viral replication and transcription, is target here. The study show that, from the electronic features and binding affinity of all the NPs with the enzyme, the compounds with higher hydrophobicity and lower flexibility can be more favorable inhibitor. More than fifty NPs were screened for the target and one terpenoid (T3) from marine sponge Cacospongia mycofijiensis shows excellent SARS CoV-2 Mpro inhibitory activity in comparison with known peptide based inhibitors. The molecular dynamics simulation studies of the terpenoids with the protein indicates that the complex is stable and hydrogen bonds are involved during the complexation. Considering binding affinity, bioavailability, pharmacokinetics and toxicity of the compounds, it is proposed that the NP T3 can act as a potential drug candidate against COVID-19 virus., Graphical Abstract Image, graphical abstract

Background: Healthcare systems are under prominent stress due to the COVID-19 pandemic. A fast and simple triage is mandatory to screen patients who will benefit from early hospitalization, from those that can be managed as outpatients. There is a lack of all-comers scores, and no score has been proposed for western-world population. Aims: To develop a fast-track risk score valid for every COVID-19 patient at diagnosis. Methods: Single-center, retrospective study based on all the inhabitants of a healthcare area. Logistic regression was used to identify simple and wide-available risk factors for adverse events (death, intensive care admission, invasive mechanical ventilation, bleeding >BARC3, acute renal injury, respiratory insufficiency, myocardial infarction, acute heart failure, pulmonary emboli, or stroke). Results: Of the total healthcare area population, 447.979 inhabitants, 965 patients (0.22%), were diagnosed with COVID-19. A total of 124 patients (12.85%) experienced adverse events. The novel SODA score (based on sex, peripheral O2 saturation, presence of diabetes, and age) demonstrated good accuracy for adverse events prediction (area under ROC curve 0.858, CI: 0.82-0.98). A cut-off value of 5 points, high-risk patients (PPV 58.8% for adverse events). Conclusions: This quick and easy score allows fast-track triage at the moment of diagnosis for COVID-19 using four simple variables: age, sex, SpO2, and diabetes. SODA score could improve preventive measures taken at diagnosis in high-risk patients and also relieve resources by identifying very low-risk patients. Funding Statement: None. Declaration of Interests: The authors declare that there is no conflict of interest regarding the publication of this article. Ethics Approval Statement: This study complied with the edicts of the 1975 Declaration of Helsinki and was approved by the institutional ethics of the institution.

Highlights • Nitric oxide gas and donors are promising candidates for antiviral therapies. • Combined with dual antimicrobial and antithrombotic properties. • Emerging therapies are undergoing clinical trials. • Potential to develop medical device surfaces resistant to viral contamination, Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating vascular physiology. The generation of NO from the upregulation of endogenous nitric oxide synthases serves as an efficacious method for inhibiting viral replication in host defense and warrants investigation for the development of antiviral therapeutics. With increased incidence of global pandemics concerning several respiratory-based viral infections, it is necessary to develop broad therapeutic platforms for inhibiting viral replication and enabling more efficient host clearance, as well as to fabricate new materials for deterring viral transmission from medical devices. Recent developments in creating stabilized NO donor compounds and their incorporation into macromolecular scaffolds and polymeric substrates has created a new paradigm for developing NO-based therapeutics for long-term NO release in applications for bactericidal and blood-contacting surfaces. Despite this abundance of research, there has been little consideration of NO-releasing scaffolds and substrates for reducing passive transmission of viral infections or for treating several respiratory viral infections. The aim of this review is to highlight the recent advances in developing gaseous NO, NO prodrugs, and NO donor compounds for antiviral therapies; discuss the limitations of NO as an antiviral agent; and outline future prospects for guiding materials design of a next generation of NO-releasing antiviral platforms., Graphical Abstract Image, graphical abstract

Purpose of review: Although the respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is evident from recent data that other systems, especially cardiovascular and hematological, are also significantly affected. In fact, in severe form, COVID-19 causes a systemic illness with widespread inflammation and cytokine flood, resulting in severe cardiovascular injury. Therefore, we reviewed cardiac injury biomarkers' role in various cardiovascular complications of COVID 19 in recent studies. Recent findings: Cardiac injury biomarkers were elevated in most of the complicated cases of COVID-19, and their elevation is directly proportional to the worst outcome. Evaluation of cardiac biomarkers with markers of other organ damage gives a more reliable tool for case fatalities and future outcome. Summary: Significant association of cardiac biomarkers in COVID-19 cases helps disease management and prognosis, especially in severely ill patients.

BACKGROUND: The effect of solid organ transplantation (SOT) on the severity and mortality of coronavirus disease 2019 (COVID-19) remained controversial. There is still no consensus on whether solid organ transplantation (SOT) recipients with COVID-19 are at greater risk of developing severe or fatal COVID-19. Therefore, we conducted a systematic review and meta-analysis to investigate the association between SOT, severe COVID-19 illness, and mortality. METHODS: A systemically comprehensive search in Pubmed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure was performed for relevant studies and articles. Consequently, we pooled the odds ratio (OR) from individual studies and performed heterogeneity, quality assessment and subgroup/sensitivity analysis. RESULTS: A total number of 15 articles with 265,839 participants were included in this study. Among the total number of participants, 1485 were SOT recipients. The meta-analysis results showed that transplant patients with COVID-19 were remarkably associated with a higher risk of intensive care unit admission than non-transplant patients (OR = 1.57, 95%CI: 1.07 to 2.31, P = 0.02). On the other hand, there were no statistically significant differences between SOT recipients and non-SOT recipients in mechanical ventilation need (OR = 1.55, 95%CI: 0.98 to 2.44, P = 0.06). In addition, we found that SOT recipients with COVID-19 had 1.40-fold increased odds of mortality than non-SOT recipients (OR = 1.40, 95%CI: 1.10 to 1.79, P = 0.007). Moreover, pooled analysis of adjusted results revealed that SOT recipients had a greater risk of mortality compared with non-SOT patients (HR = 1.54, 95%CI: 1.03 to 2.32, P = 0.037). LIMITATIONS: The main limitations in our study are attributed to the relatively small sample size, short follow-up period, and the fact that most of the studies included were retrospective in design. CONCLUSIONS: The results of this study indicate that SOT recipients with COVID-19 had a more significant risk of COVID-19 severity and mortality than the general population.

Highlights • Currently, chest computed tomography is recommended as the first-line imaging test for detecting COVID-19 pneumonia. • The most typical CT imaging finding of COVID-19 patients is ground-glass opacity, combined with reticular and/or interlobular septal thickening and consolidation. • CT is useful for monitoring patients with COVID-19, identifying associated vascular abnormalities and making differential diagnosis., With the rapid spread of COVID-19 worldwide, early detection and efficient isolation of suspected patients are especially important to prevent the transmission. Although nucleic acid testing of SARS-CoV-2 is still the gold standard for diagnosis, there are well-recognized early-detection problems including time-consuming in the diagnosis process, noticeable false-negative rate in the early stage and lacking nucleic acid testing kits in some areas. Therefore, effective and rational applications of imaging technologies are critical in aiding the screen and helping the diagnosis of suspected patients. Currently, chest computed tomography is recommended as the first-line imaging test for detecting COVID-19 pneumonia, which could allow not only early detection of the typical chest manifestations, but also timely estimation of the disease severity and therapeutic effects. In addition, other radiological methods including chest X-ray, magnetic resonance imaging, and positron emission computed tomography also show significant advantages in the detection of COVID-19 pneumonia. This review summarizes the applications of radiology and nuclear medicine in detecting and diagnosing COVID-19. It highlights the importance for these technologies to curb the rapid transmission during the pandemic, considering findings from special groups such as children and pregnant women.

Highlights • Epidemiological studies conclude diabetes to be a leading comorbidity of COVID-19. • ACE2 polymorphisms in host can influence SARS-CoV-2 susceptibility or resistance. • The in-silico data need to be corroborated with in-vivo results. • Telemedicine can bring a new change in diabetes care., Background Diabetes has been found to be one of the leading comorbidities associated with fatality in COVID-19 patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry is facilitated by interaction with Angiotensin Converting Enzyme-2 (ACE2) and possible polymorphisms in ACE2 can be a determining factor in host-viral protein interaction. A significant shift of healthcare towards ‘Telemedicine’ is also on the rise. In this review, the possible effects of ACE2 polymorphisms on SARS-CoV-2 entry along with the escalation of ‘telemedicine’ is discussed. Method An expansive literature search using keywords: “COVID-19”, “SARS-CoV-2”, “diabetes”, “type 2 diabetes’’, “type 1 diabetes”, “ACE2”, “polymorphism”, “DPP4” and “telemedicine” was conducted on Pubmed and EMBASE till 7th August 2020. Result Possible polymorphisms in ACE2 gene can play a role in influencing the virus entry in host body. Telemedicine can bring a new revolution for medical sector. Conclusion COVID-19 severity is more heinous among diabetic population. So far, the in-silico studies involving human ACE2-viral Spike (S) interaction showed inconsistent predictions regarding some SNPs. But without actual in-vivo studies, a holistic understanding can’t be established.

SARS-CoV-2 is mutating and creating divergent variants by altering the composition of essential constituent proteins. Pharmacologically, it is crucial to understand the diverse mechanism of mutations for stable vaccine or anti-viral drug design. Our current study concentrates on all the constituent proteins of 469 SARS-CoV-2 genome samples, derived from Indian patients. However, the study may easily be extended to the samples across the globe. We perform clustering analysis towards identifying unique variants in each of the SARS-CoV-2 proteins. A total of 536 mutated positions within the coding regions of SARS-CoV-2 proteins are detected among the identified variants from Indian isolates. We quantify mutations by focusing on the unique variants of each SARS-CoV-2 protein. We report the average number of mutation per variant, percentage of mutated positions, synonymous and non-synonymous mutations, mutations occurring in three codon positions and so on. Our study reveals the most susceptible six (06) proteins, which are ORF1ab, Spike (S), Nucleocapsid (N), ORF3a, ORF7a, and ORF8. Several non-synonymous substitutions are observed to be unique in different SARS-CoV-2 proteins. A total of 57 possible deleterious amino acid substitutions are predicted, which may impact on the protein functions. Several mutations show a large decrease in protein stability and are observed in putative functional domains of the proteins that might have some role in disease pathogenesis. We observe a good number of physicochemical property change during above deleterious substitutions.

The sudden outbreak of COVID-19 has once again shrouded people in the enormous threat of RNA virus. Extracellular vesicles (EVs), eukaryotic cells-derived small bi-layer vesicles mainly consisting of exosomes and microvesicles, share many properties with RNA viruses including structure, size, generation, and uptake. Emerging evidence has implicated the involvement of EVs in the pathogenesis of infectious diseases induced by RNA viruses. EVs can transfer viral receptors (e.g., ACE2 and CD9) to recipient cells to facilitate viral infection, directly transport infectious viral particles to adjacent cells for virus spreading, and mask viruses with a host structure to escape immune surveillance. Here, we examine the current status of EVs to summarize their roles in mediating RNA virus infection, together with a comprehensive discussion of the underlying mechanisms.

International audience; COVID-19 is described in a clinical case involving a patient who proposed the hypothesis that Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-interacting nutrients may help to prevent severe COVID-19 symptoms. Capsules of broccoli seeds containing glucoraphanin were being taken before the onset of SARS-CoV-2 infection and were continued daily for over a month after the first COVID-19 symptoms. They were found to reduce many of the symptoms rapidly and for a duration of 6-12 h by repeated dosing. When the patient was stable but still suffering from cough and nasal obstruction when not taking the broccoli capsules, a double-blind induced cough challenge confirmed the speed of onset of the capsules (less than 10 min). A second clinical case with lower broccoli doses carried out during the cytokine storm confirmed the clinical benefits already observed. A third clinical case showed similar effects at the onset of symptoms. In the first clinical trial, we used a dose of under 600 μmol per day of glucoraphanin. However, such a high dose may induce pharmacologic effects that require careful examination before the performance of any study. It is likely that the fast onset of action is mediated through the TRPA1 channel. These experimental clinical cases represent a proof-of-concept confirming the hypothesis that Nrf2-interacting nutrients are effective in COVID-19. However, this cannot be used in practice before the availability of further safety data, and confirmation is necessary through proper trials on efficacy and safety.

An epidemic of acute respiratory syndrome (Covid-19) started in humans in Wuhan in 2019, and became a pandemic. Groups from China Identified and sequenced the virus responsible for COVID-19, named SARS-CoV-2, and determined that it was a novel coronavirus (CoV) that shared high sequence identity with bat- and pangolin-derived SARS-like CoVs, suggesting a zoonotic origin. SARS-CoV-2 is a member of Coronaviridae, a family of enveloped, positive-sense, single-stranded RNA viruses that infect a broad range of vertebrates. The rapid release of the sequence of the virus has allowed the development of diagnostic tools (e.g., RT-PCR). Additionally, serological tests can allow identification of persons who have been infected. In humans, CoVs tend to cause mild to moderate upper respiratory tract infections. The fatality rate is around 1-3% for infected persons. An acute respiratory distress syndrome (ARDS) likely due to an uncontrolled immune activation (“cytokine storm”) occurs in patients with severe disease and poor prognosis. Risk factors for mortality include: advanced age, obesity, diabetes, hypertension and other comorbidities. Drug repurposing has been used to rapidly identify potential treatment for COVID-19, which could move quickly to phase-3. Better knowledge of the virus, its enzymes, will be mandatory to develop more potent and specific direct-acting antiviral agents (DAA). In the long term, a vaccine to prevent infection would be crucial; however even if successful it might not be available before 2021-22. To date, with the exception of intravenous Remdesivir and dexamethasone, which have modest effects in moderate to severe COVID-19, no strong clinical evidence supports the efficacy and safety of any other drugs against SARS-CoV-2. The aim of this review is to provide insights on the discovery of SARS-CoV-2, its virology, the diagnostic tools, and the ongoing drug discovery effort.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)., Highlights • In December 2019, a novel coronavirus of SARS-CoV-2 emerged in Wuhan, Hubei, China, rapidly dispersed and even exported to neighboring countries. • SARS-CoV-2 generally causes a mild lower respiratory tract infection in humans, however, in some sever cases, signs of dysfunctions in multiple organs have been discovered. • Overproduction of cytokines, termed cytokine storm, may involve in disease progression and even be responsible for deaths. • Application of immune-modulators might become a complement to support treatment and flip on the light switch for severe patients.

Background and Aims Diabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19. Methods and Results – Diabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19-1.45], 2.11 [1.83-2.44], 2.45 [1.96-3.07], 1.87 [1.68-2.09], all p

Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies ((f)AABs) targeting G-protein coupled receptors (GPCR-(f)AABs) has been discussed to be involved. We, therefore investigated, whether GPCR-(f)AABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-(f)AABs that acted as receptor agonists. Some of those GPCR-(f)AABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-(f)AAB detection). Other GPCR-(f)AABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-(f)AABs identified in the blood of Long-COVID patients targeted the β(2)-adrenoceptor (β(2)-(f)AAB), the α1-adrenoceptor (α(1)-(f)AAB), the angiotensin II AT1-receptor (AT1-(f)AAB), and the nociceptin-like opioid receptor (NOC-(f)AAB). The negative chronotropic GPCR-(f)AABs identified targeted the muscarinic M(2)-receptor (M(2)-(f)AAB), the MAS-receptor (MAS-(f)AAB), and the ETA-receptor (ETA-(f)AAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.

Bioflavonoids are the largest group of plant-derived polyphenolic compounds with diverse biological potential and have also been proven efficacious in the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The present investigation validates molecular docking, simulation, and MM-PBSA studies of fifteen bioactive bioflavonoids derived from plants as a plausible potential antiviral in the treatment of COVID-19. Molecular docking studies for 15 flavonoids on the three SARS CoV-2 proteins, non-structural protein-15 Endoribonuclease (NSP15), the receptor-binding domain of spike protein (RBD of S protein), and main protease (Mpro/3CLpro) were performed and selected protein-ligand complexes were subjected to Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-PBSA method. All flavonoids were further assessed for their effectiveness as adjuvant therapy by network pharmacology analysis on the target proteins. The network pharmacology analysis suggests the involvement of selected bioflavonoids in the modulation of multiple signaling pathways like p53, FoxO, MAPK, Wnt, Rap1, TNF, adipocytokine, and leukocyte transendothelial migration which plays a significant role in immunomodulation, minimizing the oxidative stress and inflammation. Molecular docking and molecular dynamics simulation studies illustrated the potential of glycyrrhizic acid, amentoflavone, and mulberroside in inhibiting key SARS-CoV-2 proteins and these results could be exploited further in designing future ligands from natural sources., Graphical abstract Image 1, Highlights • Bioflavonoids are potential antiviral secondary metabolites. • Docking, MD and network pharmacology demonstrated antiviral & adjuvant potential. • MM-PBSA calculations and network pharmacology identified key bioflavonoids. • Mulberroside, Glycyrrhizic acid and Amentoflavone may hold promise in COVID-19.

Objective To report the cognitive features of severe COVID-19 patients entering in the post-acute phase, to understand whether COVID-19 acute respiratory distress syndrome itself could result in long-term cognitive deficits and whether neuropsychological treatment after the acute stage might represent a specific rehabilitation need. Design Case series. Setting Rehabilitation hospital. Participants We assessed the general cognitive functioning, through tablet-supported video-call, in 9 of 12 consecutive patients admitted to the hospital at least 30 days earlier for acute respiratory distress syndrome due to COVID-19. None of these patients presented cognitive symptoms before the hospitalization. Main Outcome Measures General Cognitive functioning, measured using the Mini-Mental State Examination Test. Results A general cognitive decay was observed in three patients (33.3%), who had a pathological score at the Mini-Mental State Examination (MMSE), with a specific decline in attention, memory, language and praxis abilities. The cognitive (mal)functioning seems to be linearly associated with the length of stay (in days) in the intensive care unit (ICU): the higher the number of days spent in the ICU, the lower the MMSE score (indicating a lower global cognitive functioning). Conclusions Our results indicate that some COVID-19 patients might also benefit from a neuropsychological rehabilitation, given their possible global cognitive decay. The link between the neuropsychological functioning and the length of stay in the ICU suggests that neurocognitive rehabilitative treatments should be directed explicitly towards patients who are treated in the ICU care, rather than towards every patient who suffered from acute respiratory distress syndrome due to COVID-19. However, given the limitation of a case series study, those hypotheses should be tested with future studies with larger samples and a longer follow-up., Highlights • General cognitive decline was observed in severe COVID-19 patients. • The decline linearly associates with the length of stay in the ICU. • Some COVID-19 patients might benefit from a neuropsychological rehabilitation.

Background On March 2020, World Health Organization (WHO) declared COVID-19 to be a pandemic disease. Interactions between allergy-related inflammatory and psychiatric disorders including depression, anxiety, and post-traumatic stress disorder (PTSD) have been documented. Therefore, those who have pre-existing allergic conditions may have an increased psychiatric reaction to the stresses of the COVID-19 pandemic. Objective Identify the psychological impact of COVID-19 in patients with allergic diseases and determine if these individuals have a greater risk of presenting with post-traumatic stress disorder (PTSD). Methods It is a cross-sectional, survey-based study designed to assess the degree of symptoms of depression and the risk of PTSD using the Patient Health Questionnaire (PHQ-9) and the Impact of Event Scale–Revised (IES-R), respectively, in allergic patients. Results A total of 4106 surveys were evaluated; 1656 (40.3%) were patients with allergic disease, and 2450 (59.7%) were non-allergic (control) individuals. Of those with allergies, 76.6% had respiratory allergic disease including asthma and allergic rhinitis. Individuals with allergic disease reported higher scores regarding symptoms of PTSD on the IES-R scale (p = 0.052, OR 1.24 CI 0.99–1.55) as well as a higher depression risk score in the PHQ-9 questionnaire (mean 6.82 vs. 5.28) p = 0.000 z = −8.76. The allergy group presented a higher score in the IES-R questionnaire (mean 25.42 vs. 20.59), being more susceptible to presenting PTSD (p = 0.000, z = −7.774). The individuals with allergic conditions were further divided into subgroups of those with respiratory allergies such as allergic rhinitis and asthma vs those with non-respiratory allergies such as drug and food allergy, urticaria and atopic dermatitis. This subgroup analysis compares respiratory versus non-respiratory allergic patients, with similar results on the IES-R (mean 25.87 vs 23.9) p = 0.0124, z = −1.539. There was no significant difference on intrusion (p = 0.061, z = −1.873) and avoidance (p = 0.767, z = −0.297), but in the hyperarousal subscale, patients with respiratory allergy had higher scores (mean 1.15 vs. 0.99) p = 0.013 z = −2.486. Conclusions Psychological consequences such as depression and reported PTSD are present during the COVID-19 pandemic causing an impact particularly in individuals with allergic diseases. If we acknowledge the impact and how it is affecting our patients, we are able to implement interventions, follow up, and contribute to their overall well-being.

SARS-CoV-2-induced COVID-19 is a serious pandemic of the 21st century, which has caused a devastating loss of lives and a global economic catastrophe. A successful vaccine against SARS-CoV-2 has suffered a delay due to lack of substantial knowledge about its mechanisms of action. Understanding the innate immune system against SARS-CoV-2 and the role of heat shock proteins' (HSP) inhibiting and resolution of inflammatory pathways may provide information to the low SARS-CoV-2 mortality rates in Africa. In addition, bats being a host to different viruses, including SARS-CoV-2 possess a well specialized IFN-innate antiviral inflammatory response, showing no signs of disease or pro-inflammatory cytokine storm. We discuss the molecular pathways in COVID-19 with a focus on innate immunity, inflammation, HSP responses, and suggest appropriate candidates for therapeutic targets and The contribution of the innate immune system to the efficacy of mRNA or vector based Corona immunizations.

Graphical abstract, Coronaviruses are a major infectious disease threat, and include the zoonotic-origin human pathogens SARS-CoV-2, SARS-CoV, and MERS-CoV (SARS-2, SARS-1, and MERS). Entry of coronaviruses into host cells is mediated by the spike (S) protein. In our previous ESR studies, the local membrane ordering effect of the fusion peptide (FP) of various viral glycoproteins including the S of SARS-1 and MERS has been consistently observed. We previously determined that the sequence immediately downstream from the S2’ cleavage site is the bona fide SARS-1 FP. In this study, we used sequence alignment to identify the SARS-2 FP, and studied its membrane ordering effect. Although there are only three residue difference, SARS-2 FP induces even greater membrane ordering than SARS-1 FP, possibly due to its greater hydrophobicity. This may be a reason that SARS-2 is better able to infect host cells. In addition, the membrane binding enthalpy for SARS-2 is greater. Both the membrane ordering of SARS-2 and SARS-1 FPs are dependent on Ca2+, but that of SARS-2 shows a greater response to the presence of Ca2+. Both FPs bind two Ca2+ ions as does SARS-1 FP, but the two Ca2+ binding sites of SARS-2 exhibit greater cooperativity. This Ca2+ dependence by the SARS-2 FP is very ion-specific. These results show that Ca2+ is an important regulator that interacts with the SARS-2 FP and thus plays a significant role in SARS-2 viral entry. This could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel.

The novel corona virus disease or COVID-19 caused by a positive strand RNA virus (PRV) called SARS-CoV-2 is plaguing the entire planet as we conduct this study. In this study a multifaceted analysis was carried out employing dinucleotide signature, codon usage and codon context to compare and unravel the genomic as well as genic characteristics of the SARS-CoV-2 isolates and how they compare to other PRVs which represents some of the most pathogenic human viruses. The main emphasis of this study was to comprehend the codon biology of the SARS-CoV-2 in the backdrop of the other PRVs like Poliovirus, Japanese encephalitis virus, Hepatitis C virus, Norovirus, Rubella virus, Semliki Forest virus, Zika virus, Dengue virus, Human rhinoviruses and the Betacoronaviruses since codon usage pattern along with the nucleotide composition prevalent within the viral genome helps to understand the biology and evolution of viruses. Our results suggest discrete genomic dinucleotide signature within the PRVs. Some of the genes from the different SARS-CoV-2 isolates were also found to demonstrate heterogeneity in terms of their dinucleotide signature. The SARS-CoV-2 isolates also demonstrated a codon context trend characteristically dissimilar to the other PRVs. The findings of this study are expected to contribute to the developing global knowledge base in countering COVID-19.

In the absence of vaccines and antiviral drugs available to prevent and treat COVID-19, it becomes imperative to find or use all those products with the potential to fight this virus. This article is an attempt to propose ways to prevent, treat and control the COVID-19 virus, using a product based on plant extracts with the potential to reduce the symptoms caused by the SARS-CoV-2 virus. Nasoil® counts as one of its main components, Asclepias curassavica extracts, and in the present study it has been shown that it is an effective adjuvant in the treatment of Covid-19, increasing the respiratory capacity of the patients (SpO2> 90%) and reducing the symptoms from the first application, improving the patients around the fifth to the eighth application. At a preventive level, the individuals in this study who have applied it (400 individuals) only a 3.15% of these presented symptoms, disappearing when increasing the weekly applications., Graphical abstract Image 1, Highlights • Nasoil® protects from the appearance of symptoms by 96% due to Covid-19. • Modifying lung microenvironments reduces Covid-19 symptoms. • Promoting new interactions in the elastic protein decreases the elastase activity of neutrophils. • The combination of plant extracts in Nasoil® help in respiratory problems. • Nasoil® is an co-adjuvant for the control and prevention of the SARS-CoV-2 virus.

Background Corticosteroid therapy is used commonly in patients with coronavirus disease 2019 (COVID-19), although its impact on outcomes and which patients could benefit from corticosteroid therapy are uncertain. Research Question Are clinical phenotypes of COVID-19 associated with differential response to corticosteroid therapy? Study Design and Methods Critically ill patients with COVID-19 from Tongji Hospital treated between January and February 2020 were included, and the main exposure of interest was the administration of IV corticosteroids. The primary outcome was 28-day mortality. Marginal structural modeling was used to account for baseline and time-dependent confounders. An unsupervised machine learning approach was carried out to identify phenotypes of COVID-19. Results A total of 428 patients were included; 280 of 428 patients (65.4%) received corticosteroid therapy. The 28-day mortality was significantly higher in patients who received corticosteroid therapy than in those who did not (53.9% vs 19.6%; P < .0001). After marginal structural modeling, corticosteroid therapy was not associated significantly with 28-day mortality (hazard ratio [HR], 0.80; 95% CI, 0.54-1.18; P = .26). Our analysis identified two phenotypes of COVID-19, and compared with the hypoinflammatory phenotype, the hyperinflammatory phenotype was characterized by elevated levels of proinflammatory cytokines, higher Sequential Organ Failure Assessment scores, and higher rates of complications. Corticosteroid therapy was associated with a reduced 28-day mortality (HR, 0.45; 95% CI, 0.25-0.80; P = .0062) in patients with the hyperinflammatory phenotype. Interpretation For critically ill patients with COVID-19, corticosteroid therapy was not associated with 28-day mortality, but the use of corticosteroids showed significant survival benefits in patients with the hyperinflammatory phenotype.

Background The receptor binding domain (RBD) of spike protein S1 domain SARS-CoV-2 plays a key role in the interaction with ACE2, which leads to subsequent S2 domain mediated membrane fusion and incorporation of viral RNA into host cells. In this study we tend to repurpose already approved drugs as inhibitors of the interaction between S1-RBD and the ACE2 receptor. Methods 2456 approved drugs were screened against the RBD of S1 protein of SARS-CoV-2 (target PDB ID: 6M17). As the interacting surface between S1-RBD and ACE2 comprises of bigger region, the interacting surface was divided into 3 sites on the basis of interactions (site 1, 2 and 3) and a total of 5 grids were generated (site 1, site 2, site 3, site 1+site 2 and site 2+site 3). A virtual screening was performed using GLIDE implementing HTVS, SP and XP screening. The top hits (on the basis of docking score) were further screened for MM-GBSA. All the top hits were further evaluated in molecular dynamics studies. Performance of the virtual screening protocol was evaluated using enrichment studies. Result and discussion: We performed 5 virtual screening against 5 grids generated. A total of 42 compounds were identified after virtual screening. These drugs were further assessed for their interaction dynamics in molecular dynamics simulation. On the basis of molecular dynamics studies, we come up with 10 molecules with favorable interaction profile, which also interacted with physiologically important residues (residues taking part in the interaction between S1-RBD and ACE2. These are antidiabetic (acarbose), vitamins (riboflavin and levomefolic acid), anti-platelet agents (cangrelor), aminoglycoside antibiotics (Kanamycin, amikacin) bronchodilator (fenoterol), immunomodulator (lamivudine), and anti-neoplastic agents (mitoxantrone and vidarabine). However, while considering the relative side chain fluctuations when compared to the S1-RBD: ACE2 complex riboflavin, fenoterol, cangrelor and vidarabine emerged out as molecules with prolonged relative stability. Conclusion We identified 4 already approved drugs (riboflavin, fenoterol, cangrelor and vidarabine) as possible agents for repurposing as inhibitors of S1:ACE2 interaction. In-vitro validation of these findings are necessary for identification of a safe and effective inhibitor of S1: ACE2 mediated entry of SARS-CoV-2 into the host cell., Graphical abstract Image 1, Highlights • The receptor binding domain (RBD) of spike S1 protein of SARS-CoV-2 plays a key role in the interaction with ACE2. • In this study we tend to repurpose already approved drugs as inhibitors of the interaction between S1-RBD and the ACE2 receptor. • A virtual screening of approved drugs (n=2456) were performed using GLIDE implementing HTVS, SP and XP screening (target PDB ID: 6M17). • The top hits (n=42, on the basis of docking score) were further screened for MM-GBSA and molecular dynamics simulation studies. Performance of the virtual screening protocol was evaluated using enrichment studies. • On the basis of molecular dynamics studies, we come up with 10 molecules with favorable interaction profile. These are antidiabetic (acarbose), vitamins (riboflavin and levomefolic acid), anti-platelet agents (cangrelor), aminoglycoside antibiotics (Kanamycin, amikacin) bronchodilator (fenoterol), immunomodulator (lamivudine), and anti-neoplastic agents (mitoxantrone and vidarabine). • However, while considering the relative side chain fluctuations, riboflavin, fenoterol, cangrelor and vidarabine emerged out as molecules with prolonged relative stability.

In February 2020, the exponential growth of COVID-19 cases in Wuhan city posed a huge economic burden to local medical systems. Consequently, Wuhan established Fangcang Shelter hospitals as a One Health approach for responding to and containing the COVID-19 outbreak by isolating and caring for mild-to-moderate cases. However, it is unclear to what degree the hospitals contained COVID-19. This study performed an interrupted time series analysis to compare the number of new confirmed cases of COVID-19 before and after the operation of Fangcang Shelter hospitals. The initial number of confirmed cases in Wuhan increased significantly by 68.54 cases per day prior to February 4, 2020. Compared with the number of cases noted 20 days before the use of Fangcang Shelter hospitals, a sustained reduction in the number of confirmed cases (trend change, −125.57; P, Highlights • A sustained reduction and immediate increase in the number of cases were observed in Wuhan city after Fangcang Shelter hospitals were established. • The above changes resulted in an estimated 5148 fewer confirmed cases in Wuhan. • According to the mean confirmed cases of 395.71 per day before the intervention, we estimated that Wuhan had advanced the terminal phase of COVID-19 by 13 days. • Compared to the approximate real-time effective reproduction number [R(t)] of 4.0 in the pre-operation periods of Fangcang Shelter hospitals, the R(t) was less than 2.0 in the post-operation periods.

Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19., Highlights • Host cell cholesterol is required for efficient viral infection. • NPC and ORPs regulate cholesterol exit from endolysosomes and viral infection. • Endosomal phospholipid BMP interacts with sterol transport proteins NPC and ORPs. • BMP by controlling cholesterol trafficking could be involved in virus infection. • BMP could be a potential therapeutic target for COVID-19.

Objective To study the adrenocortical response to an acute coronavirus disease-2019 (COVID-19) infection. Methods Morning plasma cortisol, adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate levels were measured in 28 consecutive patients with COVID-19 (16 men, 12 women, median age 45.5 years, range 25-69 years) on day 1 to 2 of hospital admission. These tests were repeated twice in 20 patients and thrice in 15 patients on different days. The hormone levels were correlated with severity of the disease. Results The median morning cortisol level was 196 (31-587) nmol/L. It was

Background The traditional Chinese Medicine (TCM) herbal formula Lian Hua Qing Wen (LHQW) improves the results of COVID-19 treatment. Three very recent studies analyzed with network pharmacology some working mechanisms of LHQW. However, we used more techniques and also included Angiotensin converting enzyme 2 (ACE2) (a SARS-CoV receptor, possibly the viral entry point in alveolar lung cells) and the immune system, as cytokine storm is essential in the late phase. Purpose Extensive detailed Network Pharmacology analysis of the LHQW- treatment mechanism in COVID-19. Methods TCM-herb-meridian and protein interaction network (PIN) of LHQW, based on LHQW herbs meridian information and the protein-protein interaction (PPI) information of the LHQW-component targets. Hub and topological property analyses to obtain crucial targets and construct the crucial LHQW-PIN. Functional modules determination using MCODE, GO and KEGG pathway analysis of biological processes and pathway enrichment. Intersection calculations between the LHQW-proteins and ACE2 co-expression-proteins. Results LHQW herbs have relationships to Stomach-, Heart-, Liver- and Spleen-systems, but most (10 of the 13 herbs) to the Lung system, indicating specific effects in lung diseases. The crucial LHQW PIN has the scale-free property, contains 2,480 targets, 160,266 PPIs and thirty functional modules. Six modules are enriched in leukocyte-mediated immunity, the interferon-gamma-mediated signaling pathway, immune response regulating signaling pathway, interleukin 23 mediated signaling pathway and Fc gamma receptor-mediated phagocytosis (GO analysis). These 6 are also enriched in cancer, immune system-, and viral infection diseases (KEGG). LHQW shared 189 proteins with ACE2 co-expression proteins. Conclusions Detailed network analysis shows, that LHQW herbal TCM treatment modulates the inflammatory process, exerts antiviral effects and repairs lung injury. Moreover, it also relieves the “cytokine storm” and improves ACE2-expression-disorder-caused symptoms. These innovative findings give a rational pharmacological basis and support for treating COVID-19 and possibly other diseases with LHQW., Graphical abstract Image, graphical abstract

Highlights • Lycorine inhibited MERS-CoV, SARS-CoV, and SARS-CoV-2 infections. • Lycorine directly inhibited MERS-CoV RdRp activity. • Lycorine interacts with SARS-CoV-2 RdRp through hydrogen bonding. • Lycorine is a non-nucleoside direct-acting antiviral against emerging coronavirus., Graphical abstract Image, graphical abstract, Background: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Hér.) Herb. and has various pharmacological bioactivities including antiviral function. Purpose: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections. Methods: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp. Results: Lycorine efficiently inhibited these CoVs with IC50 values of 2.123±0.053, 1.021±0.025, and 0.878±0.022 μM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC50 of 1.406 ± 0.260 μM, compared with remdesivir's IC50 value of 6.335 ± 0.731 μM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (−6.2 kcal/mol) were higher than those of remdesivir (−4.7 kcal/mol). Conclusions: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.

Technology is advancing progressively at a very sharp rate in every phase of the commercial and economic issues, where energy plays a vital role in hi-tech enrichment. After continuous and multi directive research, human is efficient enough to put their steps on the peak of all imaginable pitches. But a human cannot fight against the environment in all instances. COVID-19, or Corona Virus, is such a type of environmental pandemic. Due to a large spread rate of COVID-19, the human society of the entire Globe is getting affected within a very small period. During its first and second wave, it collapses maximum countries health, economic structures along with the electrical sector. Many countries have enforced the ‘lockdown’ to their citizen for minimizing the community spread rate, which directly affects the energy sector. Standing in this scenario, this study focuses on the significant effect of COVID-19 on the energy sector of the Globe, especially in India. This paper also demonstrates that how several countries are trying to secure their power sector in this pandemic situation.

Summary: Background: Indigenous peoples are vulnerable to pandemics, including to the coronavirus disease (COVID)-19, since it causes high mortality and specially, the loss of elderly Indigenous individuals. Methods: The epidemiological data of severe acute respiratory syndrome (SARS) by SARS-CoV-2 infection or other etiologic agents (OEA) among Brazilian Indigenous peoples during the first year of COVID-19 pandemic was obtained from a Brazilian Ministry of Health open-access database to perform an observational study. Considering only Indigenous individuals diagnosed with SARS by COVID-19, the epidemiology data were also evaluated as risk of death. The type of sample collection for virus screening, demographic profile, clinical symptoms, comorbidities, and clinical evolution were evaluated. The primary outcome was considered the death in the Brazilian Indigenous individuals and the secondary outcome, the characteristics of Brazilian Indigenous infected by SARS-CoV-2 or OEA, as the need for intensive care unit admission or the need for mechanical ventilation support. The statistical analysis was done using Logistic Regression Model. Alpha of 0.05. Findings: A total of 3,122 cases of Indigenous individuals with SARS in Brazil were reported during the first year of the COVID-19 pandemic. Of these, 1,994 were diagnosed with COVID-19 and 730/1,816 (40.2%) of them died. The death rate among individuals with SARS-CoV-2 was three-fold increased when compared to the group of individuals with OEA. Several symptoms (myalgia, loss of smell, and sore throat) and comorbidities (cardiopathy, systemic arterial hypertension, and diabetes mellitus) were more prevalent in the COVID-19 group when compared to Indigenous individuals with OEA. Similar profile was observed considering the risk of death among the Indigenous individuals with COVID-19 who presented several symptoms (oxygen saturation