The pandemic history of pathogenic SARS-CoV-2 associated COVID-19 infection began in December 2019, with its emergence in Wuhan, China. Pertaining to its high transmissibility and wide host adaptability, this new and unique human coronavirus spread across the planet affecting almost every country, inflicting 91 million people and causing 1.9 million deaths (as of January 17th, 2021). Limited or negligible pre-existing immunity to multiple SARS-CoV-2 variants has resulted in severe morbidity and mortality worldwide, as well as a record-breaking surge in the use of medical-surgical supplies and personal protective equipments. In response to the global need for effective sterilization techniques, this study evaluated the virucidal efficacy of FATHHOME’s self-contained, ozone-based dry-sanitizing device, by dose and time response assessment. We tested inactivation of human coronavirus, HCoV-OC43, a close genetic model of SARS-CoV-2, on porous (N95 filtering facepiece respirator/FFR) and nonporous (glass) surfaces. We started our assays with 20 ppm of ozone for 10 min exposure, which was able to effectively reduce, 99.8% and 99.9% of virus from glass and N95 FFR surfaces, respectively. Importantly, the virus was completely inactivated, below the detection limit (over 6-log10 reduction) with 25 ppm ozone for 15 mins on both tested surfaces. As expected, a higher ozone concentration (50 ppm) resulted in faster inactivation of HCoV-OC43 with 100% inactivation in 10 mins from both the surfaces, with no residual ozone present after completion of the 5-minute post exposure recapture cycle and no measurable increase in ambient ozone levels. These results confirmed that FATHHOME’s device may provide a safe and viable solution for rapid decontamination of SARS-CoV-2- from worn items, frequently touched items, and PPE including N95 FFRs, face shields and other personal items.

Cannabis has long been used for its medicinal and psychoactive properties. With the relatively new adoption of formal medicinal cannabis regulations worldwide, the study of cannabinoids, both endogenous and exogenous, has similarly flourished in more recent decades. In particular, research investigating the role of cannabinoids in regeneration and neurodevelopment has yielded promising results in vertebrate models. However, regeneration-competent vertebrates are few, whereas a myriad of invertebrate species have been established as superb models for regeneration. As such, this review aims to provide a comprehensive summary of the endocannabinoid system, with a focus on current advances in the area of endocannabinoid system contributions to invertebrate neurodevelopment and regeneration.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests themselves, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.

Knowing the “point of view” of the immune system is essential to understand the characteristic of a pandemic, such as that generated by the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2, responsible for the Coronavirus Disease (COVID)-19. In this review, we will discuss the general host/pathogen interactions dictating protective immune response or immunopathology, addressing the role of immunity or immunopathology in influencing the clinical infection outcome, and debate the potential immunoprophylactic and immunotherapy strategies required to fight the virus infection.

Trophoblast cell-surface antigen 2 (Trop 2) is a transmembrane glycoprotein that is highly expressed in various cancer types with relatively low or no baseline expression in most of normal tissues. Its overexpression is associated with tumor growth and poor prognosis; Trop 2 is therefore, an ideal therapeutic target for epithelial cancers. Several Trop 2 targeted therapeutics have recently been developed for the treatment of cancers, such as anti-Trop 2 antibodies and antibody-drug conjugates (ADCs), as well as Trop 2-specific cell therapy. In particular, the safety and clinical benefit of Trop 2-based ADCs have been demonstrated in clinical trials across multiple tumor types, including those with limited treatment options, such as triple-negative breast cancer, platinum-resistant urothelial cancer, and heavily pretreated non-small cell lung cancer. In this review, we elaborate on recent advances in Trop 2 targeted modalities and provide an overview of novel insights for future developments in this field.

With increasing fatalities, the COVID-19 pandemic constitutes a formidable global health challenge. The causative agent, SARS-CoV-2 constantly tests the efficacy of the immune system of its victims. The protective ability of the innate immune system as the first responder largely determines the progression of disease and its clinical prognosis. Evidence suggests that mortalities associated with COVID-19 are largely due to hyperinflammation and a dysregulated immune response. Consequently, the degree of the release of pro-inflammatory cytokines such as IL1, IL-6, and TNF alpha remarkably distinguishes between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for laboratory tests, and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. With respect to the SARS-CoV-2 and the host cell, this literature review focuses on the dynamics of the COVID-19 disease highlighting on the pathogenesis, and the markers of Cytokine Storm. It also proffers solutions by critically looking at the current and potential pharmacological agents that are or can be used to mitigate and manage cytokine storms.

Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. In addition, DPP4 binds to the spike protein of MERS virus, causing it to be the human cell surface receptor for that virus. DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion exchange chromatography. The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor binding domain (RBD) were measured using surface plasmon resonance and ELISA. This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS-CoV, SARS-CoV-2 does not bind human DPP4.

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.

The novel coronavirus diseases 2019 (COVID-19) has unfolded an unprecedented worldwide public health emergency with disastrous economic consequences. Around 12 million coronavirus cases have already been identified with over half a million deaths. Despite numerous efforts by the government as well as international organizations, these numbers are still increasing with a surprising rate. Although urgent and absolutely necessary, a reliable therapeutic or vaccine is still elusive and this status quo may remain for an uncertain period of time. Taken that into account, boosting up adaptive immunity through nutritional interventions may help subside this epidemic and save many lives. This review focuses on the nexus between a balanced diet and adaptive immunity, particularly, how a poor diet may lead to compromised immunity resulting in susceptibility to viral infections. Additionally, we discuss how nutrients (vitamins, minerals, trace elements) could be used as a tool to modulate immune response and thus impede viral infections. The study also summarized nutritional recommendations to combat COVID-19 in different countries and territories and dietary sources of those key nutrients. Moreover, different nutritional intervention strategies based on different age groups, physiological and medical conditions were also included, and the challenges of nutritional interventions towards the care of COVID-19 patients were also discussed. Since the availability of a drug or vaccine is still uncertain, a balanced diet or nutrient therapy could be used as a robust strategy to combat COVID-19. Thus, we hope this review may help to make an informed decision with regard to diet choice both at individual level as well as clinical settings.

We present the Lagrangian and Hamiltonian formulations of a theory for spin 2 fields. The construction is developed in flat space-time. The construction in curved space-time is conceptually straightforward, although it is not unique. The theory is based on a symmetric tensor $S_{\mu\nu}$, contains two degrees of freedom of radiation, is motivated by the teleparallel formulation of general relativity, and displays a certain resemblance with Maxwell's theory for the electromagnetic field.

Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after varies of respiratory viruses infection such as influenza A virus (IFV), respiratory syncytial virus (RSV) and human rhinovirus (hRV). Our analyses reveal that infection of multiple kinds of respiratory viruses or influenza vaccines greatly increased ACE2 expression, suggesting that respiratory viruses infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.

We analyzed the characteristics of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infected children during lock-down period in Catalonia (Spain), and their transmission role within the households. Among 295 traced household contacts of 89 pediatric patients, children were classified as final index cases in only 3.4% of the traced homes.

In this work, pure TiO₂ and binary nanocomposites of Fe₃O₄/TiO₂ and Ag/TiO₂ were synthesized in order to improve photocatalytic performance of these samples for degradation of 2, 4-dichlorophenol (2, 4-DCP) as an organic pollutant. A range of analytical techniques including XRD, DRS, SEM/EDX, and elemental mapping were employed to reveal the crystal structure, morphology and property of the nanocomposites. XRD data demonstrated that the prepared samples are purely in TiO₂ anatase phase and cubic spinel Fe₃O₄ exist in the synthesized nanocomposite. We calculated the TiO₂ crystal size from XRD patterns, in the range of 8.35-11.09 nm. The presence of Ag, Fe, O, and Ti atoms in the synthesized nanocomposites was confirmed by SEM/EDX. We obtained 30.43, 32.02 and 42.40 % degradation of 2, 4-DCP (100 ml 2, 4-DCP 40 ppm and 0.01 g catalyst) for pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively, after 180 min of irradiation under visible light. Similar conditions were employed for 2, 4-DCP degradation under UV irradiation, we obtained 53.05, 51.00 and 71.50 % degradation of 2, 4-DCP pure TiO₂, Fe₃O₄/TiO₂ and Ag/TiO₂, respectively. Thus, the synthesized binary nanocomposites exhibited higher photocatalytic activity compared to pure TiO₂ under visible light.

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

Background SARS-CoV-2 has generated a life-treating pandemic and is the main challenge of this century. Some untranslated regions (UTRs) in SARS-CoV-2 genome, specifically leader sequence and transcription regulatory sequence (TRS) in 5’UTR, can be considered as Achilles' heel of virus. Leader sequence are found at the 5' ends of all encoded transcripts that highlights its importance. TRS can explain the host range and pathogenicity of coronavirus. However, our knowledge on the evolution and the role of UTRs in SARS-CoV-2 pathogenicity is very limited. This study is a pioneering attempt to unravel the evolution of key regions in 5' UTR of SARS-CoV-2 and discover the inhibitory microRNAs against 5' UTR of virus. Methods Evolution of TRS and leader sequence was compared between human pathogenic (SARS-CoV-2, SARS, and MERS) and non-pathogenic (bovine) coronaviruses. Profiling of microRNAs that can inactive the key UTR regions of coronaviruses, UTR-inhibitory microRNAs, was carried out. Findings We found a distinguished pattern of evolution in leader sequence and TRS of SARS-CoV-2, compared to the other coronaviruses. Mining all available microRNA families against leader sequences of coronaviruses resulted in discovery of 39 microRNAs with an acceptable thermodynamic binding energy against SARS-COV-2, SARS, MERS, Bat Coronavirus, or Bovine Coronavirus. Multivariate analysis demonstrated a distinguished pattern of binding of leader sequence of SARS-CoV-2 against microRNAs, with a lower binding stability. hsa-MIR-5004-3p was the only human microRNA that can target leader sequence of SARS and SARS-CoV-2. However, its binding stability remarkably decreased in SARS-COV-2 (-19.4 kcal/mol), compared to SARS-COV-2 (-25.9 kcal/mol). We found an insertion-type mutation in leader sequence of SARS-COV-2 that results in lower binding stability and escaping of viral leader sequence from hsa-MIR-5004-3p. Altogether, we suggest lack of innate human inhibitory microRNAs to bind to leader sequence and TRS of SARS-CoV-2 contributes to its high replication in infected human cells. On the other hand, mining of two hundred million deposited human genomic variants led us to discovery of 49 missense and splice-disrupt mutations in genomic structure of hsa-MIR-5004-3p. These mutations can negatively affect hsa-MIR-5004-3p function in preventing SARS-CoV-2 replication. Interpretation This study unravels the evolution of key regions in 5’UTR of SARS-CoV-2. Inducing microRNAs to bind to the leader sequence and TRS regions by drugs or food supplements can reduce virus replication. Enhancing the microRNA defence machinery against TRS and leader of virus has a potential to prevent SARS-CoV-2 infection at the first place. The mentioned strategy is rapidly achievable against COVID-19. Missense variation in genomic sequence of 5’UTR inhibitory microRNAs, such as hsa-MIR-5004-3p, can be considered as risk factor of COVID-19.

Motivation by the definition of the type 2 poly-Bernoulli polynomials introduced by Kim-Kim [9], in the present paper, we consider a new class of new generating function for the Fubini polynomials, called the type 2 poly-Fubini polynomials by means of the polyexponential function. Then, we derive some useful relations and properties. We show that the type 2 poly-Fubini polynomials equal a linear combination of the classical of the Fubini polynomials and Stirling numbers of the first kind. In a special case, we give a relation between the type 2 poly-Fubini polynomials and Bernoulli polynomials of order r. Moreover, inspired by the definition of the unipoly-Bernoulli polynomials introduced by Kim-Kim [9]. We introduce the type 2 unipoly-Fubini polynomials by means of unipoly function and give multifarious properties including derivative and integral properties. Furthermore, we provide a correlation between the unipoly-Fubini polynomials and the classical Fubini polynomials.

There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

Hepatic encephalopathy is a complex life-threatening neuropsychiatric syndrome, which can be associated with acute inflammation. It can be found in cases of acute liver failure caused by a viral infection. Reports of patients infected with SARS-CoV-2 have described hepatic encephalopathy. Therapy with immunomodulators can be an effective choice for this clinical condition. CIGB-258 is an immunomodulatory peptide with anti-inflammatory properties derived from cellular stress protein 60 (HSP60). We report a case of a 55-years-old woman diagnosed with COVID-19 and hepatic encephalopathy characterized by episodes of anxiety, delirium, confusion and seizure, according to her clinical history, laboratory and radiological data. Levels of aspartate aminotransferase, alanine aminotransferase , plasma ammonia and alkaline phosphatase were increased and inflammatory biomarkers such as interleukin 6 and 10 were over the normal range. The patient received an intravenous administration of 1 mg of CIGB-258, every 12 hours during four days, followed by 1 mg daily for another three days without adverse reactions. Neurological symptoms disappeared completely at by the fourth days after starting therapy, and inflammatory biomarkers noticeably decreased, but not all of them reach the normal values. This case highlights the outcomes of a severe COVID-19 patient with hepatic encephalopathy, treated with CIGB-258. The patient recovered successfully and the liver enzymes, plasma ammonia and biomarkers associated with hyperinflammation were reduced. These results support clinical investigations of CIGB-258 as a therapeutic agent in COVID-19.TRIAL REGISTRATION: RPCEC00000313

Since the discovery of the first reported case with Zinc-deficiency in Iran¹ by Prasad et al. in 1961, the knowledge on Zinc has increased significantly. Zinc is the second most abundant common trace mineral in the human body, responsible for vital biological functions from cell growth and development to cell homeostasis and immune response ^2,3. Up to a fifth of the global population is estimated to suffer from different degrees of Zinc deficiency⁴. In the western world, Zinc deficiency is more prevalent among the geriatric population³, vegans/vegetarians, and people with certain underlying conditions⁴such as liver cirrhosis, inflammatory bowel disease, and various auto-immune disorders^4,5. Zinc and Zinc deficiency has been associated with several infectious diseases ^2,3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for the ongoing pandemic belongs to the family of coronaviruses. SARS-CoV-2 has a high genetic similarity to another family member, SARS-CoV, which caused the first major epidemic of the 21^st century^6,7. Currently, there is no evidence linking the anti- SARS-CoV-2 response and the element Zinc. Herein and in light of the SARS-CoV-2 pandemic, we marshal the evidence associating the element Zinc with the anti-viral and antibacterial immune response as well as the cytokine storm and lung injury. Such a revisit of the precedent evidence may inspire further investigation assessing the relationship between Zincemia status and the anti-viral response in SARS-CoV-2 patients.

Coronaviruses are positive sense RNA virus belonging to the Coronaviridae family, which are further subdivided into four genera: Alpha, Beta, Gamma, and Delta Coronaviruses. Infectious bronchitis virus and SARS-CoV belong to Beta Coronaviridae family. Infectious bronchitis virus causes respiratory and nephritic signs that includes tracheal rales, urate crystals, lethargy and nasal discharge. In livestock and pets, the Coronavirus infection causes mostly gastrointestinal lesions, which may be prevented through vaccination and biosecurity. Recent infections of SARS-CoV-2 (also known as COVID-19) on farm and pet animals were summarized in this study. Besides, zoo animals were reported with infections in some countries/regions. Although the damage of COVID-19 has not been reported as serious as highly pathogenic avian influenza (HPAI) and African Swine Fever (ASF) on farm animals so far, the transmission mechanism of COVID-19 among group animals/farms and its long-term impacts are still not clear. The impact of Coronavirus on animals and potential prevention strategies, such as vaccine development and farm biosecurity measures, were discussed. Prior to the development of the effective vaccine, the biosecurity measures (e.g., conventional disinfection strategies and innovated technologies) may play roles in preventing potential spread of diseases/viruses.

Rats fed a high-fat diet with a single streptozotocin (STZ) injection developed obesity, prediabetes, cardiac hypertrophy and diastolic dysfunction. Here we aimed to explore the renal consequences of prediabetes in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or high-fat diet containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 cardiac functions were examined (Koncsos et al., 2016) and blood and urine samples were taken. Kidney samples were collected for histology, immunohistochemistry and for analysis of gene expression. High-fat diet and streptozotocin increased body weight gain and visceral adiposity, and plasma leptin, elevated fasting blood glucose levels, impaired glucose and insulin tolerance, despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1β mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression and cortical and medullary mRNA expression of TGF-β1, Nrf2, PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while serum lipid and liver enzyme levels were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury.

Novel SARS-CoV-2, a bat based virus originated in Wuhan, China that caused a global pandemic in December, 2019 belongs to the Betacorona virus family and contains single stranded genome of ~29Kbp. The host cell invasion of SARS-CoV-2 is facilitated by interaction of C-Terminal Domain (CTD) of Spike (S) protein of virus and host ACE2 receptor in the presence of TMPRSS seine protease secreted by the host cell. In this study the mutation hotspots of S-protein will be identified and the impact of such mutation in the binding affinity will be studied. Additionally, the lead molecule which can bind to the mutated protein also will be identified. Multiple sequence alignment of the spike protein sequence of SARS-CoV-2 shows the number of single amino acid mutation hotspots such as L5F, R214L, R408I, G476S, V483A, H519Q, A520S, T572I, D614G and H655Y. Among these mutations D614G has 57.5% occurrence and G476S, V483A has 7.5% occurrence. The mutated proteins were modelled based on wild type homolog and docked to ACE2 receptor. When the mutated S protein is docked, the ∆G (binding free energy) value is very minimal in mutated protein showed the stability of variants. By the drug repurposing method, 1000 FDA approved drugs were virtually screened for its binding to RBD of S1 domain. Among these drugs Digitoxin, Gliquidone and Zorubicin Hcl binds to spike proteins with higher docking score (lesser than -8.5 Kcal/mol) to both wild type and mutants.

The outbreak of COVID-19 started in mainland China and has rapidly spread to more than 200 countries and territories around the world (WHO, 2020). The new coronavirus is a respiratory virus and its transmission is known to occur by upper respiratory secretions, including airborne droplets after coughing or sneezing. There is no evidence to support the role of food in the transmission of COVID-19. However, sharing food in public places is not encouraged. Furthermore, standard operating procedures of food safety like thorough washing, avoid cross contamination, keeping raw and cooked foods separated, refrigeration and heating are highly suggested. The pandemic has dramatically increased food insecurity across the countries and threatens the food security and nutrition of millions of people. The review presents information about SARS-CoV-2 with respect to food, including a brief history of coronavirus, its classification and transmission. It further presents the role of food as a carrier of the virus, which looks unlikely so far but cannot be fully ruled out, food contamination and handling followed by prevention and safety measures as per the standard guidelines, and conclusive remarks.

Nine components (C1-C9) were isolated from chloroform fraction of fractionated methanol extracts of Vernonia amygdalina leaves (FMEVA) by column chromatography. All the components C1 to C9 were purified and screened for hypoglycaemic activities in type-2 diabetic rats. The most potent hypoglycaemic component was elucidated on the basis of extensive spectroscopic (1D-, 2D-NMR, GC-MS, FTIR) data analysis. The Component C5 was found to be the most potent hypoglycaemic in reducing blood glucose by 12.55 ± 3.55% at 4 h post-oral administration, when compared to the positive (18.07 ± 1.20%) and negative (-1.99 ± 0.43%) controls. The spectroscopic data analysis reveals that the isolated compound has a structure consistent with 11β,13-dihydrovernolide. The isolated compound is part of the hypoglycaemic components present in V. amygdalina leaves that is responsible for the anti-diabetic activities. Further research is needed in the development of this compound or its derivatives for pharmaceutical use.

Sentinel-2 provides the opportunity to map the snow cover at unprecedented spatial and temporal resolution at global scale. Here we calibrate and evaluate a simple empirical function to estimate the fractional snow cover (FSC) in open terrain using the normalized difference snow index (NDSI) from 20 m resolution Sentinel-2 images. The NDSI is computed from flat surface reflectances after masking cloud and snow-free areas. The NDSI-FSC function is calibrated using Pléiades very high resolution images and evaluated using independent datasets including SPOT 6/7 satellite images, time lapse camera photographs, terrestrial lidar scans and crowd-sourced in situ measurements. The calibration results show that the FSC can be represented with a sigmoid-shaped function 0.5×tanh(a×NDSI+b)+0.5 where a = 2.65 and b = -1.42 yielding a root mean square error of 25%. Similar RMSE are obtained with different evaluation datasets with a high topographic variability. With this function, we estimate that the confidence interval on the FSC retrievals is 38% at the 95% confidence level.

The severity of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), greatly varies from patient to patient. In the present study, we explored and compared mutation profiles of SARS-CoV-2 isolated from mildly affected and severely affected COVID-19 patients in order to explore any relationship between mutation profile and disease severity. Genomic sequences of SARS-CoV-2 were downloaded from GISAID database. With the help of Genome Detective Coronavirus Typing Tool, genomic sequences were aligned with the Wuhan seafood market pneumonia virus reference sequence and all the mutations were identified. Distribution of mutant variants was then compared between mildly and severely affected groups. Among the numerous mutations detected, 14,408C>T and 23,403A>G mutations resulting in RNA-dependent RNA polymerase (RdRp) P323L and spike protein D614G mutations, respectively, were found predominantly in severely affected group (>82%) compared with mildly affected group (<46%, p<0.001). The 241C>T mutation in the non-coding region of the genome was also found predominantly in severely affected group. The 3,037C>T, a silent mutation, also appeared in relatively high frequency in severely affected group. We concluded that RdRp P323L and spike protein D614G mutations predominate in severely affected COVID-19 patients. Further studies will be required to explore whether these mutations have any impact on the severity of COVID-19.

The COVID-19 global pandemic is now a public health emergency in Morocco. Reports on factors associated with prolonged viral shedding are not consistent. In this retrospective laboratory based study, time to RNA negative conversion is reported in a series of 129 patients monitored in a single laboratory in Casablanca. Risk factors associated with delayed negative conversion have been evaluated, by chi-squared test. Median delay of negative conversion was 22.5 days (IQR 17.75-29.0) from illness onset. Neither gender nor age were particularly associated with delayed viral clearance. Delayed time to hospital admission and disease severity were associated with prolonged viral shedding in this series. We recommend early diagnosis and treatment onset to reduce time to viral clearance and transmissibility of SARS-CoV-2 virus.

We are proposing, for any interested investigator, a randomized open clinical trial for mild and mild-to-moderate Covid-19 comparing a treatment regimen with standard of care, and eventually with another investigational regimen, if ongoing or will be implemented. The patients could be hospitalized or ambulatory but not requiring admission to intensive care units and mechanical ventilation. The proposed therapeutic regimen consists of doxycycline (an antimicrobial having also anti-inflammatory properties, probable antioxidant and possible some antiviral effects), and pentoxifylline, a hemorheological compound used in occlusive arterial diseases but also having proven anti-inflammatory properties. Doxycycline is included in the WHO’s list of essential medicine being an effective, safe, widely available, and inexpensive medication and widely accessible. It will be administered at a dosage of 100 mg orally twice daily for ten days. Pentoxifylline, in clinical use since 1972, and also widely accessible, will be given at a dosage of 400 mg orally, also twice daily, for ten days. The primary outcome measures are: 1) Progression of disease to a severe form requiring intensive care admission and mechanical ventilation; 2) Fatality rates and 3) Time to clinical recovery.This proposal was presented to the National Directors and Core Leads meeting of the Canadian Trials Network (CTN) on May 6, 2020. The interventional trial template suggested by CTN was used for designing the trial.

Three patients with severe life-threatening COVID-19 who failed to achieve substantial improvement on tocilizumab, received pulse therapy with corticosteroids (methylprednisolone, 1000 mg/day IV for three consecutive days) and intravenous immunoglobulin (20 g/day IV). This was associated with a prompt resolution of respiratory failure, elimination of cytokine release syndrome, and reversal of pulmonary CT changes. The treatment was generally safe and well tolerated. There was no evidence of protracted persistence of the virus in the patients who received pulse therapy. Randomized controlled trials are necessary to specify the efficacy and safety of high-dose methylprednisolone and intravenous immunoglobulin in the treatment of severe life-threatening COVID-19 separately or in combination.

Purpose of this article is to project from the point of view of the scientific data concerning PAF and as a new approach by involving PAF, in order to contribute to clarification and proposal a possible mechanism of action of the coronavirus SARS-CoV-2 and to give a possible explanation for its observed side effects-complications of Covid-19 disease. The article is not intended to suggest any specific drugs, but clarifying the mechanism is the first step in illuminating the direction of prescribing the targets of medication that may be appropriate for the prevention, treatment, and cure of Covid-19 disease. More specifically, the purpose of this article is to provide unequivocal evidence indicating that: 1 It would not be unexpected for PAFR to participate in the entry of coronavirus SARS-CoV-2 into the cell. 2 There is interdependence and relationship of the receptors ACER and PAFR, which means the involvement of PAF in the processes related to coronavirus SARS-CoV-2 as well as to its effects exercised by the coronavirus SARS-CoV-2. 3 The receptors ACER, PAFR and TLRs are also involved in inflammation as well as in virus binding to stabilize and enter into the cell, and so they are "communicating vessels" with PAF being " a missing link" 4 Consequently there is a correlations of COVID-19 disease manifestations and biological characteristics with those caused by PAF, which shows the involvement of PAF in COVID-19 disease.

The 2019 novel SARS-like coronavirus (SARS-CoV-2) entry depends on the host membrane serine protease TMPRSS2, which can be blocked by some clinically-proven drugs. Here we analyzed spatial relevance between glycosylation sequons and antibody epitopes and found that, different from SARS-CoV S, most high-surface-accessible epitopes of SARS-CoV-2 S are blocked by the glycosylation, and the optimal epitope with the highest surface accessibility is covered by the S1 cap. TMPRSS2 inhibitor treatments may prevent unmasking of this epitope and therefore prolong virus clearance and may induce antibody-dependent enhancement. Interestingly, a heparin-binding sequence immediately upstream of the S1/S2 cleavage site has been found in SARS-CoV-2 S but not in SARS-CoV S. Binding of SARS-CoV-2 with heparins may lead to exposure of S686, which then facilitates the S1/S2 cleavage, induces exposure of the optimal epitope, and therefore increases the antibody titres. A combination of heparin and vaccine (or convalescent serum) treatments thus is recommended.

The objective of this study was to review the study design and preliminary results of the Recovery trial and analyze the implementability of the Recovery trial by comparing it with the European Discovery trial.Method: The study design of the Recovery trial in the latest version of protocol was described and deeply analyzed to address the issue of implementation of the trial. A comparative analysis of study design and implementation between the UK Recovery trial and the European Discovery trial was conducted following the description.Results: The Recovery trial is a pragmatic, randomized, controlled, adaptive, open-label clinical trial. The study design of the Recovery trial was reported in the ISRCTN registry, the EU Clinical Trials Register and the U.S. National Library of Medicine ClinicalTrials.gov registry. Initially published on the 13^th March 2020, the study protocol of the Recovery trial has been updated five times at the time of this writing. More than 11,000 patients have been enrolled and 80% have completed the follow-up. Thousands of health care professionals at 175 Trusts in the UK have been involved. Conclusion: The Recovery trial applies a study design to address the issue of implementation in the context of the COVID-19 pandemic and emergency. It was conceptually pragmatic with a clear vision to address the top priority: the control of mortality and rational use of scarce resources. By contrast, the Discovery trial was designed as an intellectual exercise and consequently failed to address the issue of implementation in emergency.

There is a new public health crisis threatening the world with the emergence and spread of novel coronavirus (SARS-CoV-2). The outbreak of coronavirus disease 2019 (COVID-19), which originated in Wuhan, China, in December 2019, has been declared a public health emergency of international concern by WHO. Most patients infected with SARS-CoV-2 exhibited symptoms of fever, cough, myalgia, fatigue and shortness of breath. Many infected people may be asymptomatic. It is generally believed that airway exposure to respiratory droplets from an infected patient is the main transmission route of this disease. However, apart from respiratory source, other source specimens like faecal matter and urine could be possible for COVID-19 infectivity. The spreading other routes of the virus has been alarming sign, both for public and health care professionals. Understanding the spreading routes of SARS-CoV-2 is crucial for patient management and defining biosafety strategies for public and health care workers.

This study developed a system dynamics model to understand the spread of coronavirus disease (COVID-19) in Japan. The model is built on the generic SEIR (Susceptible, Exposed, Infected, and Recovered) framework adopted by Ghaffarzadegan and Rahmandad (2020) to build a system dynamics model for the spread of COVID-19 in Iran. Japan seems to be successful in containing the spread compared with other countries, and its first peak has passed. However, because this also leaves a large population still susceptible to the virus, it could cause a second and potentially higher peak of infection after the state of emergency aimed at reducing contact rate is lifted. As the government has proposed the “New Lifestyle,” it is critical to behave cautiously so as not to be infected. While the model focuses on the SEIR structure, the reflection of other sub-structures such as economy and hospital capacity that have tradeoffs with reducing contact rate should be beneficial. However, before extending the model, it is also critical to conduct estimates using confidence intervals rather than point estimates to better reflect uncertainties.

The challenge regarding COVID-19 is to prevent complications and fatal evolution. Azithromycin (AZM) and hydroxychloroquine (HCQ) have proven their antiviral effect in vitro. We aimed to assess the efficacy and safety of AZM alone or combined to HCQ, prescribed, at an early stage, in patients with Covid-19, in a primary care setting. Eighty-eight patients received either no or a symptomatic treatment (NST) (n=34) or AZM alone (n=34) or AZM+HCQ (n=20). The efficacy end point was the time to clinical recovery and the safety end point was the occurrence of cardiovascular events. The mean (SD) times to achieve clinical recovery were respectively 25.8 days (11.1), 12.9 days (13.4) and 9.2 days (9.3), showing a statistically significant difference between NST and AZM alone (p<0.0001) or AZM+HCQ (p<0.0001). To improve the evidence level, a case-control analysis was performed on a sample of 57 patients (19/group) matched for age, sex and BMI. The statistical difference between NST and AZM was confirmed (p=0.0149) as well as the difference with AZM+HCQ (p=0.0002). No cardiac toxicity was recorded in any patient. No statistical difference was shown between AZM and AZM+HCQ groups, although the dual therapy tended to be more effective in patients over 50 years, based on an analysis using the cox model. In conclusion, AZM and AZM+HCQ favourably impacted the course of the disease. We need trials, ideally prospective/double blind, to show if a statistical difference can be evidenced with a broader group, and clarify the indications of each treatment depending on initial clinical presentation.

COVID-19, the disease caused by the new coronavirus, SARS-CoV-2, has caused significant human and economic burden. Of the three major methods to mitigate the effect of the virus, diagnostics have become the focal point because vaccines and therapeutics, despite the intense effort of scientists worldwide, will take months to develop, test for safety and efficacy, scaleup and distribute to millions. This perspective aims to clarify some of the issues related to COVID-19 diagnostics and highlights some of the challenges key stakeholders including policymakers, businesses, managers, scientists and individuals face during this evolving pandemic.

Number of confirmed cases of COVID-19 caused by SARS-CoV-2 exceeded 5 million as of May 21, 2020. Global average of the case fatality rate of COVID-19 is about 7% so far. There exist variations in case fatality rates among countries. Particularly, Singapore and Qatar have exceptionally low case fatality rates with 0.1% while France’s rate is almost 20%. Since no magic bullet treatment for COVID-19 exists, we investigated SARS-CoV-2 strains specific to Singapore in this study to identify a clade with low pathogenicity. Variant analysis revealed that a clade with variants ORF1ab L3606F, A4489V, S2015R, T2016K, and N P13L is common in Singapore. Based on our analysis of variants and historical case statistics, the clade is dominant in a recent surge. Therefore, we suggest that low case fatality rate of Singapore possibly is attributed to the clade. Although contribution of each variant to the low pathogenicity is not clear, L3606F alone does not accomplish such low pathogenicity from the comparison with case fatality data from Japan, where L3606F is dominant. Further investigation is necessary to conclude to validate this finding.

Severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has caused the global pandemic as COVID-19, which is the most notorious global public health crisis in the last 100 years. SARS-CoV-2 is composed of four structural proteins and several non-structured proteins. The multi-facet nucleocapsid (N) protein is the major component of structural proteins of CoVs, However, there are no dedicated genomic, sequences and structural analyses focusing on potential roles of N protein. Hence, there is an urgent requirement of a detailed study on N protein of SARS-CoV-2. Herein, we are presenting a comprehensive study on N protein from SARS-CoV-2. We have identified seven motifs conserved in the three major domains namely N-terminal domain, linker regions and the C-terminal domains. Out of seven motifs, six motifs are conserved across different members of coronaviridae, while motif4 is specific for SARS CoVs with potential amyloidogenic properties. Additionally, we report this protein has large patches of disordered regions flanking with these seven motifs. These motifs are hubs of epitopes with 67 experimentally verified epitopes from related viruses. We report the presence of three nuclear localization signals (NLS1-NLS3 mapped to 36-41, 256-26, and 363-389 residues, respectively) and two nuclear export signals (NES1-NLS2 from 151-161 and 217-230 residues, respectively) in the N protein of SARS-CoV-2. These deciphered two Q-patches as Q-patch1 and Q-patch2, mapped in the regions of 266-306, and 361-418 residues, which potentially help in the aggregation of the viral proteins along with ²¹⁹LALLLLDR²²⁶ patch. Additionally, we have identified 14 antiviral drugs potentially binding to seven motifs of N-proteins using docking-based drug discovery methods.

COVID-19 is a rapidly evolving medical emergency that has drawn global attention, unprecedented in any disease of its kind in recent times. The magnitude of the health crisis emerging from this pandemic has overwhelmed health care workers worldwide and called in for extraordinary measures to contain this virus. A simple Pubmed query on “COVID-19” returned with 12214 articles (as on May 17^th, 2020), published just within a few months. A detailed survey revealed around 250 clinical reports, 8 clinical trials, 9 meta-analyses, and 906 reviews that were published during this time span. Combining the strings “COVID-19 and Pregnancy” yielded a total of 132 reports while querying “COVID-19 and Placenta” returned with just 11 articles Even taking into considerations that few materials are in the PrePrint Server, we still have a gross under-representation of studies addressing the effect of this disease on pregnancy outcome and maternal & child health. An essential aspect of a successful pregnancy is proper placentation, where transiently invasive placental trophoblast cells invade the maternal endometrium to establish a functional feto-maternal communication. Based on the elegant study by David. E. Gordon, et al. published in Nature (April 30, 2020), which identified 332 human host proteins interacting with SARS-nCoV2 using an affinity-based purification, we interrogated several gene expression data sets available at NCBI-GEO related to trophoblast invasion and differentiation. Both of these processes are indispensable for placentation and fetal survival. Our analysis showed several overlaps with the interactome proteins implying that SARS-CoV-2 infection can affect several proteins, which are crucial for trophoblasts function. GeneMANIA and STRING based functional analysis further revealed that several of that SARS-CoV-2 interacting trophoblast proteins as a hub for the protein-protein interaction network. Our study thus elucidates the possible effect of SARS-CoV-2 infection on placenta formation and pregnancy outcome.

Since the COVID-19 caused by SARS-CoV-2 break out in Wuhan China from Dec. 2019, it has spread to hundreds of countries up to now. Scientists from all over the world have paid tremendous efforts to research and try to control the disease. Previous studies suggested that some of the wild animals could be intermediate hosts between humans and origination of SARS-CoV-2, and some companion animals of humans can be infected by SARS-CoV-2, which raised our curiosity about cross-infection of SARS-CoV-2 between animals and humans. Thus, we select some kinds of animals that might have contact with humans to estimate the susceptibility to SARS-CoV-2 in different animals by evolutionary analysis of their receptors for SARS-CoV-2. The results show that some companion animals of the Felidae family like the cat has a higher infection possibility while the species of the Rodent family like the rat and mouse having close contact with humans show an opposite result, which consist with recent animal experiments and researches. These should raise concerns about cross-infection between human and companion animals or animals having close contact with humans which might turn animals into depositaries of the coronavirus even after control of SARS-CoV-2 spreading and cause second or more waves of infections after social reopening. Another side of our results stands by the opinion that bioinformatic analysis can be consistent with experiments in some respects so that we can prevent unnecessary sacrifice of laboratory animals in future experiments.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective anti-viral therapy or vaccine currently exist, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that included in vitro and in vivo models for testing of anti-viral therapies, and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on anti-viral and adjunctive therapies currently being tested or require testing in animal models and randomized clinical trials.

The spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 150 countries in a matter of months. Even though containment measures in China have reduced new cases by more than 90%, this reduction is not the case elsewhere, as the US, Spain and Italy have come off worse-off by the spread of the virus, and there is serious concern regarding the national health systems' capacity around the world and Africa, in particular, to effectively respond to the needs of infected patients who require intensive care for the COVID-19 illness. As a result, authorities around the world have resorted to the lockdown strategy to curb the spread of the virus. Therefore, the study aimed at investigating the effect of the lockdown strategy in curbing the spread of the COVID-19 virus in Nigeria. Consequently, the study found daily relative risk increase in cases, and daily relative risk increase in mortality. Also observed is the growth in cases in areas where active measures were not taken. Further, halt in business activities has rendered many penniless and unable to provide for themselves basic amenities. The study recommends that there is need to implement community-level measures of social distancing which may include closing schools, need for individuals with COVID-19 case or respiratory symptoms be properly taken care of, trace and quarantine those who must have come in contact with affected persons and introducing stay at home palliatives for the general public.

IntroductionThe aim of this study is to describe the epidemiology of all COVID-19 patients in Vietnam and to describe the measures of disease control and prevention implemented. MethodsData were recovered from Wikipedia regarding the 2020 coronavirus pandemic in Vietnam. The period covered was from 23 January to 20 April 2020. Descriptive analysis was stratified by gender, age, country of origin, travel history, clinical symptoms and outcome. A survey of disease control and prevention measures was conducted at the Centre for Disease Control in the Thai Binh province, which is responsible for screening and isolating individuals at high risk of COVID-19. ResultsAs of 20 April 2020, Vietnam had recorded 268 confirmed COVID-19 patients. 55.2% were female. 67.9% were aged 20-49 years and 82.5% were Vietnamese. 60.4% of cases were imported from outside Vietnam. Other cases were acquired in Vietnam by individuals in close contact with imported cases. Only one patient who had not travelled had had no known contact with a confirmed case. 63.1% of patients were asymptomatic. 75.7% of patients were discharged. No deaths were recorded. The Thai Binh CDC surveyed a total of 2,203 persons at risk of COVID-19. 336 persons (15.2%) were isolated at hospitals and 1,411 (64.0%) in dedicated isolation facilities. 16.4% reported at least one respiratory symptom. No positive cases confirmed by RT-PCR have been reported in the Thai Binh province to date. ConclusionThe effect of the systematic screening and isolation strategy made it possible to limit local transmission in Vietnam. Vietnam needs to reinforce diagnostic capacities, prevention measures and provide the necessary epidemiological data on which to base interventions. The wider use of rapid serological tests is also advisable in order to be able to conduct extensive screening in the community.

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This ‘cytokine storm ‘produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1 and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.

The outbreak of coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions and has affected more than 100 countries in recent weeks. It is imperative that global healthcare systems are prepared. Containment initiatives in Jordan, on the other hand, have decreased new cases by over 63%. The Jordanian national health system has been very pleased with its ability to adequately meet the needs of the patients diagnosed with SARS-CoV-2 pneumonia, and includes intensive care. From 2 March to 14 April 2020, between 4% and 8% of active infected patients in Jordan registered daily in intensive care. The percentage is very low.

SARS-CoV-2 is a novel and highly pathogenic coronavirus, which was first diagnosed in Wuhan city, China, in 2019, and spread to 185 countries and territories, and as of April 29, 2020, more than 3.11 million cases were recorded, and more than 217,000 people were killed. Despite all worldwide efforts, there is currently no vaccine, any drugs available to protect people against deadly SARS-CoV-2 coronavirus. The world urgently needs a SARS-CoV-2 coronavirus vaccine or effective antiviral drugs to relieve the human suffering associated with the pandemic that kills thousands of people every day. The SARS-CoV-2 genome encode a non-structural proteins named as ORF1a/b, and structural proteins such as spike (S) glycoprotein, nucleocapsid protein (N), small envelop protein (E) and matrix protein (M). A number of studies have been shown that CoV spike (S) glycoprotein and nucleocapsid protein (N) could be promising targets for vaccine, antibodies and therapeutic drug development to combat with deadly, pandemic SARS-CoV-2. Purposes of the present paper is the sequence analysis and amino acid variations of structural proteins deduced from novel coronavirus SARS-CoV-2 strains, isolated in different countries. Multiple sequence alignment of S, N and E proteins from four different coronavirus species, are also described. It is expected that the data from these studies will be very useful for the the designing and development of vaccines, antibodies and therapeutic agents that can be used to combat with the highly pathogenic SARS-CoV-2 coronavirus worldwide.

There were warnings before; nevertheless the current CoVID-19 pandemic took the world by surprise: within just four month, it conquered the globe and claimed over 200'000 lives. Unprecedented governmental actions put about half of the population under curfew or lock-down. The resulting economic meltdown is expected to eliminate globally 9’000’000’000’000 (9 trillion) USD in 2020 and 2021 alone, a value roughly the size of the yearly GDP of the world’s 150 smallest economies. The resulting crises might cause mass-unemployment and a hunger pandemic later this year. This Essay analyses current statistical data of the CoVID-19 pandemic to develop a guideline for a path through the crisis, minimizing both loss of lives and economic costs. Part 1 details the current situation; part 2 develops a small set of measures, allowing a near normal life until a future vaccination campaign has reached sufficient numbers of people; and part 3 provides some important lessons for the future beyond SARS-CoV-2. The Essay leads to the following key-messages: 1) The CoVID-19 pandemic will stay for at least two more years. This is the minimum time required for a vaccination campaign to reach sufficient numbers of people. 2) The crucial element to control the pandemic is keeping case numbers under the threshold required for a functional tracing, testing & isolation (TTI) strategy. That threshold differs from country to country and strongly depends on culture and the applied tracing technology as well as available testing capacities. 3) The economic burden of a TTI strategy is moderate while fatalities are also reduced. Hence, such an approach is strongly recommended. Its implementation requires a set of simple and cost-effective measures (see figure below), which in combination seem to be sufficient to keep CoVID-2’s reproductive rate at or below 1. 4) Implementing international coordination of actions will be necessary for effective infection-chain tracing5) If case numbers are above the TTI threshold, shutdown measures remain the only option until tracing of infection chains becomes feasible again.6) In the future, neglected pandemic-related research requires a funding boost. Just 1% of the bill of the current crisis could support the research of 45’000 scientist for 20 years.

We describe a 90-year-old male presenting with disequilibrium, loss of balance and difficulty walking for three days prior to initial presentation. Interestingly, he denied cough, fever or dyspnea prior to arrival. Over the course of 48 hours, the patient developed acute respiratory distress syndrome (ARDS) requiring intubation, diagnosed with COVID-19 infection and was treated in the intensive care unit where he died. Since the initial cases in Wuhan China in Dec 2019, the medical and epidemiological communities have learned much about the presenting features, symptomatology, epidemiology, transmission and common physical, laboratory and radiological findings of this disease. Although common symptoms are already established, it is very important to learn and record atypical symptoms or presentations of this highly contagious disease. By doing so, we will be able to recognize earlier atypical symptoms and prevent the environmental exposure to Health care workers and future patients as well. We report that Central disequilibrium may be such as initial presenting sign and symptom of impending respiratory failure from SARS-CoV-2 virus. These atypical findings such as presyncope may precede common respiratory complications of SARS-CoV-2.

This document outlines best practice recommendations for an acute care physiotherapy for patients with COVID-19, with an emphasis on critical care rehabilitation including the patients in extra corporeal membrane Oxygenation (ECMO) support, developed for practice in Qatar but adaptable within any settings. This recommendation is the result of a combination of systematic evidence search, subsequent critical evaluation of retrieved evidence and consensus process. The agreed recommendations were integrated into a physiotherapy clinical reasoning algorithm. It includes recommendations on physiotherapy referral, screening, management categories and best practice recommendations. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with suspected and/or confirmed COVID-19.

An outbreak of a pandemic COVID-19 disease caused by a novel coronavirus SARS-CoV-2 has posed a serious threat to human health and the economy of the whole world. Bangladesh is one of the most densely populated countries in the world, which has also come under the attack of this viral disease. This perspective report aimed to describe the responses of Bangladesh to tackle the COVID-19, particularly on how Bangladesh is dealing with this novel viral disease with limited resources. The first case of a COVID-19 patient was detected in Bangladesh on March 8, 2020. Since then, a total of 2,144 peoples are officially reported as COVID-19 infected with 84 deaths. To combat the COVID-19, the government has taken various steps to tackle the epidemic outbreak of it such as diagnosis of the suspected cases, quarantine of doubted people and isolation of infected patients, local or regional lockdown, grant general leave from all offices for staying home of people, increase public awareness and enforce social distancing and so on. In addition, to address the socio-economic situations, the government announced several financial stimulus packages of about USD 11.17 billion. However, very limited diagnostic facilities, health workers, resources such as hospital beds, personal protective equipment, intensive care unit, and ventilators in the hospitals along with limited public unawareness are the major challenges for Bangladesh to tackle the situation effectively. This report described the responses of Bangladesh to tackle the COVID-19 and discusses prevailing challenges to mitigate this highly contagious disease with limited resources.

Respiratory transmission is the primary route of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Angiotensin I converting enzyme 2 (ACE2) is the known receptor of SARS-CoV-2 surface spike glycoprotein for entry into human cells. A recent study reported absent to low expression of ACE2 in a variety of human lung epithelial cell samples. Three bioprojects (PRJEB4337, PRJNA270632 and PRJNA280600) invariably found abundant expression of ACE1 (a homolog of ACE2 and also known as ACE) in human lungs compared to very low expression of ACE2. In fact, ACE1 has a wider and more abundant tissue distribution compared to ACE2. Although it is not obvious from the primary sequence alignment of ACE1 and ACE2, comparison of X-ray crystallographic structures show striking similarities in the regions of the peptidase domains (PD) of these proteins, which is known (for ACE2) to interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Critical amino acids in ACE2 that mediate interaction with the viral spike protein are present and organized in the same order in the PD of ACE1. In silico analysis predicts comparable interaction of SARS-CoV-2 spike protein with ACE1 and ACE2. In addition, this study predicts from a list of 1263 already approved drugs that may interact with ACE2 and/or ACE1, potentially interfere with the entry of SARS-CoV-2 inside the host cells and alleviate the symptoms of Coronavirus disease (COVID-19).

A big race for the search for novel lead has begun due to the emergence of COVID-19 across the globe. More than 6,00,000 cases of afflicted patients worldwide has been reported till date with high mortality and morbidity. At present no approved drugs are known for COVID-19. Phylogenetic analysis present strong nucleotide sequence similarity of around 80% with SARS-CoV. Therefore, the drugs used for treating SARS-CoV and MERS are being used for SARS-CoV-2 also. Recently, the crystal structure of COVID-19 is reported and hence, we have used this tom predict the binding affinity with SARS-CoV-2-main protease and prepared a pharmacophore that may be used for future design of novel inhibitors.

We review aspects of the antibody response to SARS-CoV-2, the causative agent of the COVID- 19 pandemic. The topics we cover are relevant to immunotherapy with plasma from recovered patients and with monoclonal antibodies against the viral S-protein. The development of vaccines against SARS-CoV-2, an essential public health tool, will also be informed by an understanding of the antibody response in infected patients. Although virus-neutralizing antibodies are likely to protect, antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection. An awareness of these possibilities may benefit clinicians and the developers of antibody-based therapies and vaccines.

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Currently, drug repurposing is an alternative to novel drug development for the treatment of COVID-19 patients. The antimalarial drug chloroquine (CQ) and its metabolite hydroxychloroquine (HCQ) are currently being tested in several clinical studies as potential candidates to limit SARS-CoV-2-mediated morbidity and mortality. CQ and HCQ (CQ/HCQ) inhibit pH-dependent steps of SARS-CoV-2 replication by increasing pH in intracellular vesicles and interfere with virus particle delivery into host cells. Besides direct antiviral effects, CQ/HCQ specifically target extracellular zinc to intracellular lysosomes where it interferes with RNA-dependent RNA polymerase activity and coronavirus replication. As zinc deficiency frequently occurs in elderly patients and in those with cardiovascular disease, chronic pulmonary disease, or diabetes, we hypothesize that CQ/HCQ plus zinc supplementation may be more effective in reducing COVID-19 morbidity and mortality than CQ or HCQ in monotherapy. Therefore, CQ/HCQ in combination with zinc should be considered as additional study arm for COVID-19 clinical trials.

Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

Spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) made a historic transition between December 2019 to March 2020. In the present scenario SARS-CoV-2 as becomes a major burden on public health and economic stability of societies around the globe. From the substantial evidences gained from the pandemic of SARS-CoV-2 and MERS-CoV (Middle East respiratory syndrome coronavirus), scientists and clinicians strongly believes that these pathogenic viruses share common homology of some biologically active enzymes which includes RNA-dependent RNA polymerase (RdRP), 3-chymotrypsin-like protease (3CL^pro), papain-like protease (PL^pro) etc. RdRP relatively grabs higher level of clinical importance in comparison with other enzyme target. Indian system of traditional medicine pioneering the therapy towards infectious disease since several centuries. In view of this potential therapeutic leads from some of the Indian medicines along with standard drug favipiravir subjected to docking investigation targeting SARS-CoV-2- RNA dependent RNA polymerase (RdRp). Residual proximity analysis reveals 18 out of 28 compounds reveals potential binding affinity of about 100% with the target amino acid residue (618 ASP, 760 ASP,761 ASP), 7 out of 28 reveals 75% binding efficacy and 3 out of 28 reveals 25% binding efficacy with that of the target residue. Hence further clinical validation may be warranted with proper in-vitro and in-vivo studies prior to the clinical recommendation in treating COVID-19 patient’s.

The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its spread to the whole world is currently posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARS-CoV based on the genome sequence comparison. Despite the genomic similarity between SARS-CoV and SARS-CoV-2, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows considerable difference compared to SARS-CoV, due to the presence of several point mutations. We analyzed the receptor binding domain (RBD) from recently published 3D structure of spike glycoprotein of SARS-CoV-2 and compared with RBD of SARS-CoV. The observations highlight few important features of RBD in the light of the recently published findings from the 3D structures of spike glycoprotein and its complex with human angiotensin-converting enzyme 2 (ACE2) (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)).

Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prion-like domains are critical for virulence and the development of therapeutic targets; however, the prion-like domains in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in the SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike protein, since SARS-CoV-2 was the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of the spike protein is particularly interesting, since although the SARS-CoV-2 and SARS-CoV S proteins share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. Finally, we identified prion-like domains in the α1 helix of the ACE2 receptor that interact with the viral receptor-binding domain of SARS-CoV-2. Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interact with RBD have important functional roles in viral adhesion and entry.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

Pneumonia caused by a new coronavirus SARS-CoV-2 has caused serious harm to people's lives and health in Wuhan, China. By February 26, 2020, over 80,000 people were infected and 2,814 died from the infection. The initial route of infection is the binding of the spike protein (S protein) of the virus to the angiotensin-converting enzyme 2 (ACE2). From bioinformatics analysis, we found that the S protein of SARS-CoV-2 produced an evolutionary mutation of K403R compared with the S protein of SARS-CoV, forming an adjacent RGD motif at the interaction surface. As the RGD motif is considered as a ligand for many cell surface integrins, we proposed that the binding of S protein of SARS-CoV-2 with integrins may facilitate the infection process of the virus. Therefore, high-throughput virtual screening was performed by choosing the key residues of S protein interface of SARS-CoV-2 and the adjacent RGD motif as potential binding site, to search for the potential agents targeting interaction of S protein of SARS-CoV-2 with both ACE2 and integrins as potential therapeutic drugs. Various libraries including the FDA-approved drugs etc. were screened, and Nadide, Losartan, 9'''-Methyllithospermate B and Leonurine etc. were identified as representative potential drugs candidate for COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a new viral respiratory disease and whether pregnant women are at increased risk of infection is unknown. Viral pneumonia is an important indirect cause of maternal death. Little is known about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Objective: To describe the clinical characteristics of COVID-19 in pregnancy and their newborn infant, and we sought to explored whether the SARS-CoV-2 can be intrauterine vertically transmitted. Study Design: The study was a case series study conducted in the obstetric ward of Tongji Hospital affiliated to Huazhong University of science and technology, Wuhan, China. Demographic, clinical, laboratory and radiological profiles of the SARS-CoV-2 infection case series. A systematic testing procedure for SARS-CoV-2 infection using oropharyngeal swab, placenta tissue, vaginal mucus, and breast milk of mothers. and oropharyngeal swab, umbilical cord blood, and serum of newborns was conducted. Results: We have conducted the most thorough virological assessment to date, and we include a longer clinical observation in mother-infant dyads during hospitalization. The clinical course and outcomes of three pregnant women who acquired SARS-CoV-2 infection late pregnancy are described in mother-infant dyads. Two had caesarean delivery in their third trimester. All patients showed an uneventful perinatal course, and a successful outcome. No infants became infected by vertical transmission or during delivery. Conclusion: No evidence to suggest the potential risk of intrauterine vertical transmission in the case series and further in-depth study is needed. Both the pregnancy woman and infant showed fewer adverse maternal and neonatal outcomes.

Proper satellite-based crop monitoring applications at the farm-level often require near-daily imagery at medium to high spatial resolution. The synthesizing of ongoing satellite missions by ESA (Sentinel 2) and NASA (Landsat7/8) provides this unprecedented opportunity at a global scale; nonetheless, this is rarely implemented because these procedures are data demanding and computationally intensive. This study developed a complete stream processing in the Google Earth Engine cloud platform to generate harmonized surface reflectance images of Landsat7,8 and Sentinel 2 missions. The harmonized images were generated for two agriculture schemes in Bekaa (Lebanon) and Ninh Thuan (Vietnam) during the period 2018-2019. We evaluated the performance of several pre-processing steps needed for the harmonization including image co-registration, brdf correction, topographic correction, and band adjustment. This study found that the miss-registration between Landsat 8 and Sentinel 2 images, varied from 10 meters in Ninh Thuan, Vietnam to 32 meters in Bekaa, Lebanon, and if not treated, posed a great impact on the quality of the harmonized dataset. Analysis of a pair overlapped L8-S2 images over the Bekaa region showed that after the harmonization, all band-to-band spatial correlations were greatly improved from (0.57, 0.64, 0.67, 0.75, 0.76, 0.75, 0.79) to (0.87, 0.91, 0.92, 0.94, 0.97, 0.97, 0.96) in bands (blue, green, red, nir,swir1,swir2, ndvi) respectively. We demonstrated that dense observation of the harmonized dataset can be very helpful for characterizing cropland in highly dynamic areas. We detected unimodal, bimodal and trimodal shapes in the temporal NDVI patterns (likely cycles of paddy rice) in Ninh Thuan province only during the year 2018. We fitted the temporal signatures of the NDVI time series using harmonic (Fourier) analysis. Derived phase (angle from the starting point to the cycle's peak) and amplitude (the cycle's height) were combined with max-NDVI to generate an R-G-B image. This image highlighted croplands as colored pixels (high phase and amplitude) and other types of land as grey/dark pixels (low phase/amplitude). Generated harmonized datasets that contain surface reflectance images (bands blue, green, red, nir, swir1, swir2, and ndvi at 30 meters) over the two studied sites are provided for public usage and testing.

Background and Objectives: Ischemic and idiopathic heart failure are two different etiologies, however reactive cardiac fibrosis together with impaired vasculogenesis has been described in both of them. Implication of main proangiogenic factors as: angiogenin, agiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) has been described mainly in experimental models of heart failure. However, differences in molecular pathways between these cardiomyopathies are still under investigation. In this short communication we aimed to evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic and idiopathic etiology. Methods and Results: Heart tissue from left ventricular walls was obtained at transplantation from ischemic heart disease (IHD), idiopathic cardiomyopathy (ICM) patients. Tissue samples were examined using immunohistochemistry for angiogenic molecules. Immunopositivity (I-pos) for angiopoietin-1 was mainly observed in the cardiomyocytes, while I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Procollagen-I (PICP), angiogenin, Ang-1, Tie-2 receptor, were similarly expressed in IHD and ICM patients. In contrast, endothelial immunopositivity for Ang-2 was higher in IHD samples compared to ICM (p=0.03). Conclusions: Ang-2 expression is different in heart tissue of ICM and ICM patients and distribution of Ang-1 and angiogenin is higher in cardiomyocytes, whereas Ang-2 higher in endothelial cells, suggesting a different pattern of angiogenic stimulation, or at least of altered endothelial integrity. This data may serve for further studies investigating angiogenesis signaling pathways and in HF of different etiology.

Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to be associated with complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with induction of cell death. However, previous studies suggest that the virally-induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to interfere with apoptosis whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell.

The Sentinel-2 satellite mission offers high resolution multispectral time series image data, enabling the production of detailed land cover maps globally. At this scale, the trade-off between processing time and result quality is a central design decision. Currently, this machine learning task is usually performed using pixelwise classification methods. The radical shift of the computer vision field away from hand engineered image features and towards more automation by representation learning comes with many promises, including higher quality results and less engineering effort. In this paper we assess fully convolutional neural networks architectures as replacements for a Random Forest classifier in an operational context for the production of high resolution land cover maps with Sentinel-2 time series at the country scale. Our contributions include a framework for working with Sentinel-2 L2A time series image data, an adaptation of the U-Net model for dealing with sparse annotation data while maintaining high resolution output, and an analysis of those results in the context of operational production of land cover maps.

The reaction mechanism of the carboxylation of K-2-naphthoxide was investigated by density functional theory calculations and spectroscopic studies. The reaction intermediates and products were confirmed by CO₂ adsorbed-FTIR and ¹H-NMR measurements. Four steps of the reaction pathway were identified: CO₂ activation, electrophilic substitution, CO₂-K complex rearrangement, and H-shift, producing 2-hydroxy-1-naphthoic acid (2,1-HNA), 2-hydroxy-3-naphthoic acid (2,3-HNA), and 2-hydroxy-6-naphthoic acid (2,6-HNA). The occurrence of CO₂-K complex rearrangement was also confirmed. These energy profiles of reaction pathways for the reaction intermediates were well consistent the experimental results on the carboxylation of K-2-naphthoxide.

A balanced chromosomal translocation disrupting DISC1 (Disrupted in Schizophrenia 1) gene has been linked to psychiatric diseases, such as major depression, bipolar disorder and schizophrenia. Since the discovery of this translocation, many studies have focused on understating the role of the truncated isoform of DISC1, hypothesizing that the gain of function of this protein could be behind the neurobiology of mental conditions, but not so many studies have focused in the mechanisms impaired due to its loss of function. For that reason, we perform an analysis on the cellular proteome of primary neurons in which DISC1 was knocked down with the goal of identifying relevant pathways directly affected by DISC1 loss of function. Using an unbiased proteomic approach, we found that the expression of 31 proteins related to neurodevelopment (e.g. CRMP-2, stathmin) and synaptic function (e.g. MUNC-18, NCS-1) is regulated by DISC1 in primary mouse neurons. Hence, this study reinforces the idea that DISC1 is a unifying regulator of both neurodevelopment and synaptic function, thereby providing a link between these two key anatomical and cellular circuitries.

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.

Lifestyle is the primary prevention of diabetes, especially type-2 diabetes (T2D). Nutritional intake of olive oil (OO), the key Mediterranean diet component has been associated with the prevention and management of many chronic diseases including T2D. Several OO bioactive compounds such as monounsaturated fatty acids, and key polyphenols including hydroxytyrosol and oleuropein, have been associated with preventing inflammation and cytokine-induced oxidative damage, glucose lowering, reducing carbohydrate absorption and increasing insulin sensitivity and related gene expression. However, research into the interaction of OO nutraceuticals with lifestyle components, especially physical activity is lacking. Promising postprandial effects have been reported when OO or other similar monounsaturated fatty acids was the main dietary fat compared with other diets. Animal studies have shown a potential anabolic effect of oleuropein. Such effects could be further potentiated via exercise, especially strength training, which is an essential exercise prescription for individuals with T2D. There is also an evidence from in vitro, animal and limited human studies for a dual preventative role of OO polyphenols in diabetes and cancer, especially that they share similar risk factors. Putative anti-oxidative and anti-inflammatory mechanisms and associated gene expressions resulting from OO phenolics, have produced paradoxical results making suggested inferences from dual prevention T2D and cancer outcomes difficult. Well-designed human interventions and clinical trials are needed to decipher such a potential dual anti-cancer and anti-diabetic effects of OO nutraceuticals. Exercise combined with OO consumption, individually or as part of a healthy diet is likely to induce reciprocal action for T2D prevention outcomes.

Rapid urbanization, increasing population and increased industrialization to cater to demands of the growing population has imposed upon us a huge environmental cost. The significantly deteriorated air quality across the globe is associated with a direct and indirect impact on public health. While associated disorders such as chronic obstructive pulmonary diseases, heart failures are well documented, less is known about the biological basis of the process. We hypothesize that the worsening air quality may likely impact common systemic inflammatory processes, thus driving communicable and non-communicable diseases alike.Receptor mediated entry of particulate matter (PM2.5) results in activation of signaling cascades which culminate in production of inflammatory chemokine and cytokine responses, traversing through the blood mediating impacting not only on other organs but also dysbiosis of microflora. For the purpose of the review we choose tuberculosis (TB) as a model for communicable infectious disease and type 2 diabetes mellitus (T2DM) as a marker for non-communicable disorder. The increasing prevalence of these co-morbidities and the burdening of public health systems justifies this example. However the hypothesis may be applicable to other inflammation driven disorders also.

New corrosion inhibitor derived from coumarin-3-amine namely 3-((2-chlorobenzylidene)amino)coumarin was synthesized and characterized by CHN elemental analysis in addition to Fourier transform infrared and nuclear magnetic resonance techniques. The anti-corrosion ability of 3-((2-chlorobenzylidene)amino)coumarin to inhibit the impacts of corrosion has been demonstrated and damage reduction of the mild steel also. 3-((2-chlorobenzylidene)amino)coumarin, has been employed as a good corrosion inhibitor for mild steel in HCL solution. The efficiency of the inhibition was figured according to weight loss method and it was 74.6%.

In this study, we investigated the effects of Akebia quinata ethanol extract (AE), Akebia quinata sikhye (AS), and Akebia quinata water extract (AW) on alcohol-induced liver injury in rats. The hepatoprotective, anti-inflammatory, anti-apoptotic, and antioxidant effects of AE, AS, and AW were examined. Experimental animals were randomly divided into five groups: normal, ethanol, AE (10 mL/kg), AS (10 mL/kg), and AW (10 mL/kg). Each group was administered the respective treatment orally once per day for 21 days. CYP2E1 mRNA expression was significantly lower in the AE, AS, and AW groups than that in the ethanol group. Pro-inflammatory cytokines including cyclooxygenase-2, IL-6, and TNF-α increased significantly in the ethanol group but these increases were ameliorated with AE, AS, and AW treatment. Moreover, the expression of the apoptosis-associated proteins Bax, p53, procaspase-3, and PARP decreased after treatment with AE, AS, and AW. The expression of antioxidant enzymes including BCL-2, SOD, and GST slightly decreased in the ethanol group, but AE, AS, and AW treatment augmented their activities. AQ extracts and AS attenuated ethanol-induced increases in the levels of phosphorylated p-AKT, p-ERK, and p-JNK. These results demonstrate that AQ is a competence indicator for inhibiting alcoholic liver injury.

In order to comprehensively evaluate the employee satisfaction of mine occupational health and safety management system, an analytic method based on fuzzy analytic hierarchy process and 2- tuple linguistic model was established. Firstly, based on the establishment of 5 first- grade indicators and 20 second- grade ones, the weight of each indicator is calculated and validated by method of FAHP and root mean square model. Secondly, a path based on the time-ordered Weighted Averaging Operator (T-OWA) model is constructed. Finally, the model is validated by empirical analysis. The results demonstrate that the employee satisfaction of the mine occupational health and safety management system is of the “general” rank. The method including the comprehensive evaluation of employee satisfaction and the quantitative analysis of language evaluation information ensures the authenticity of the language evaluation information.

Evidence suggests that COVID-19 infection increases the risk of type 1 (T1D) and type 2 diabetes (T2D). Diabetes, in turn, increases COVID-19 susceptibility and contributes to increased COVID-19 morbidity and mortality. Oxidative stress (OxS) has emerged as a common factor driving the pathogenesis of diabetes and COVID-19 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The mechanistic links between OxS, T2D, and COVID-19 have primarily been studied in adults and will be summarized in this review. However, we suggest that studying these interconnections in children and young adults is critical since early intervention is optimal for improving outcomes. At the height of the pandemic, COVID-19 was a leading cause of death in children and young people, and people in this age group are as susceptible to COVID-19 as adults and the elderly. Glutathione (GSH) is the primary water-soluble intracellular antioxidant and can be deficient in both diabetes and COVID-19. GSH is a tripeptide containing cysteine (CYS), glutamic acid (GLU), and glycine (GLY). Strategies to increase GSH levels may be beneficial in helping to manage COVID-19-induced diabetes as well as diabetes-induced COVID-19 risk. Dietary supplementation with GlyNAC may be optimal since it contains two metabolic GSH precursors, i.e., n-acetyl-l-cysteine (NAC) and GLY.

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

The stability issues in the widely known organic inorganic halide perovskite, CH₃NH₃PbI_3, lead to the development of alternative halide double perovskite materials which get great attention in recent times. Although the stability issue seems promising, both materials and device performance of these photovoltaic materials remain inferior and challenging for improvements. Furthermore, the power conversion efficiency of single junction organic inorganic halide perovskite is now 24.2% and 29.15% for textured monolithic perovskite/silicon tandem solar cell, but for all-inorganic halide perovskite solar cell is 7.11% and halide double perovskite solar cells based on Cs₂AgBiBr₆ and Cs₂TiBr₆ is 2.8% and 3.3%, respectively, which is far less than 24.2% and 29.15%, respectively. This creates big question and concern that can both all-inorganic halide perovskite solar cell and halide double perovskites solar cells really be an acceptable alternatives to replace organic inorganic halide perovskite solar cells or lead based perovskite solar cells in the market in order to realize the sustainable practical applications? Not only this concern, but also there are many other big challenges facing by halide double perovskite solar cells. Such big challenges include: a) geometric constraints and limited integration with interfacial materials, b) dynamic disorder and a wide band gap and localized conduction band caused by cubic unit cell which restrains the interactions of orbitals, c) high processing temperature which may limit on the diverse applications, d) low electronic dimensionality making them less appropriate for single junction solar cell purpose and etc. Moreover, origin of electronic and optical properties such as the polarizability, the presence of molecular dipoles and their influence on the dynamics of the photo-excitations in the halide double perovskites remains unlock concern that need to be elucidated. Now, another big question is how to develop overcoming mechanisms for such challenges. Can we really overcome these current limitations faced by halide double perovskites so that we use them for sustainable commercialization? This research roadmap for performance improvement is suggested focusing on: materials surface and bulk engineering, band gap engineering, interfacial engineering, composition engineering, doping engineering, device architectural engineering, polar and domain order engineering. This was the reason that this review was developed in order to forward great contributions to the readers and commercial ventures.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

We study here what can be learned from our experience with COVID-19 vaccination for an initially naïve population, that can inform planning for vaccination against the next novel, highly transmissible pathogen. We focus on the first two pandemic years (wild strain through Delta), because after the Omicron wave in early 2022, few people were still SARS-CoV-2-naïve. Almost all were vaccinated, infected, or often both. We review the evidence on COVID-19 vaccine effectiveness (VE), waning effectiveness over time, and what we should expect about VE and waning from a future pathogen. As a basis for our analysis, we conducted a PRISMA-compliant review of all studies on PubMed through August 15, 2022 reporting VE against four endpoints: any infection, symptomatic infection, hospitalization, and death, for the four principal vaccines used in developed Western countries (BNT162b2, mRNA1273, Ad26.CoV2.S, and ChAdOx1-S). The mRNA vaccines (BNT162b2, mRNA1273) had high initial VE against all endpoints but protection waned after approximately six months, with BNT162b2 declining faster than mRNA1273. Both mRNA vaccines initially outperformed the viral vector vaccines. A third “booster” dose, roughly six months after the primary doses, substantially reduced symptomatic infection, severe disease, and mortality, and in hindsight should be seen as part of the normal vaccination schedule.

The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species primitive as the Hydra. Insects apparently are devoid of this otherwise ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts: 1. Endogenous ligands, 2. G-protein coupled receptors (GPCRs), and 3. Enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. These are the endocannabinoids: Anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed, phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

Aim: This study sought to evaluate the effectiveness of lactate/albumin ratio for ICU mortality prediction in a large cohort of patients with severe Coronavirus Disease-2019 (COVID-19) admitted to the intensive care unit (ICU). Methods: This is a single-center retrospective cohort study of prospectively collected data derived from the COVID-19 dataset for all critically ill patients admitted to an academic ICU. Data were used to determine the relation between lactate/albumin ratio and other laboratory parameters measured on the first day of ICU stay and to evaluate the prognostic performance for ICU mortality prediction. Results: A total of 805 ICU patients were included, the median age (IQR) was 67 (57-76) years, with 68% being male. ICU mortality was 48% and the median lactate/albumin ratio was 0.53 (0.39-0.59). Survival analysis showed that patients with higher lactate/albumin ratio values had significantly lower survival rates (Log Rank p

DNA is frequently damaged by genotoxic stresses such as ionizing radiation, reactive oxygen species, and nitrogen species. DNA damage is a key contributor to cancer initiation and progression, and thus the precise and timely repair of these harmful lesions is required. Recent studies revealed transcription as a source of genome instability, and transcription-coupled DNA damage has been a focus in cancer research. Impaired mRNA export is closely related to DNA damage through R-loop formation. The molecular machineries of transcription-coupled DNA damage have been extensively analyzed in Saccharomyces cerevisiae. However, the molecular basis of these phenomena in higher eukaryotes remains elusive. In this review, we focus on the relationship between deregulated mRNA export, especially through the transcription-export-2 (TREX-2) complex, and cancer development. The expression of GANP, a key molecule in the TREX-2 complex, is highly associated with tumorigenesis in mouse and human. Additionally, we describe recent evidence for medical application that downregulation of the other components may be a good candidate for chemotherapeutic target in terms of reducing the side effects, although the involvement of R-loop is still ambiguous.

Introduction. Mexico confirmed its first COVID-19 case in February 2020. Since then, it has been important to describe the presentation and data of critically ill patients with ARDS caused by SARS-CoV-2. Objectives. To determine the survival of critically ill patients with ARDS due to SARS-CoV-2. Secondary objectives are to identify factors associated with mortality in these patients and to evaluate 90-day survival based on these risk factors. Materials and Methods. This observational, retrospective study was conducted in an ICU at a tertiary hospital in Mexico City (March 2020 - March 2023). It included patients over 18 years old with COVID-19 confirmed by PCR, excluding those with negative PCR, those who died within the first 24 hours, or those without invasive mechanical ventilation. Demographic, clinical, and treatment data were collected. Descriptive statistical analyses, logistic regression, and Kaplan-Meier analyses were performed. The study was approved by ethical committees and did not require informed consent. Results. A total of 157 patients with COVID-19 were studied, with a mean age of 62.8 years and a male predominance (74.5%). ARDS was severe in 68.2%, and acute kidney injury (AKI) developed in 70.1%. The mortality rate was 58.6%, with a 90-day survival of 33.1%. Factors such as AKI (OR = 3.4), hemodynamic failure (OR = 6.5), and elevated lactate (OR = 0.201) were independently associated with mortality, with their impact on survival confirmed by the log-rank test. Conclusion. In critically ill patients with ARDS due to COVID-19, the 90-day survival rate was 33.1%. AKI, hemodynamic failure, and elevated lactate were associated with reduced survival, especially when AKI was combined with hemodynamic failure (26.7%).

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

Background: Although confirmed cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been declining since late 2020 due to general vaccination, little research has been done regarding the impact of vaccines against SARS-CoV-2 in Spain in terms of hospitalizations and deaths. Objective: Our aim was to identify the reduction in severity and mortality of coronavirus disease 2019 (COVID-19) at a nationwide level due to vaccination. Methods: We designed a retrospective, population-based study to define waves of infection and to describe the characteristics of the hospitalized population. We also studied the rollout of vaccination and its relationship with the decline in hospitalizations and deaths. Finally, we developed two mathematical models to estimate non-vaccination scenarios using machine learning modeling (with the ElasticNet and RandomForest algorithms). The vaccination and non-vaccination scenarios were eventually compared to estimate the number of averted hospitalizations and deaths. Results: In total, 498,789 patients were included, with a global mortality of 14.3%. We identified six waves or epidemic outbreaks during the observed period. We established a strong relationship between the beginning of vaccination and the decline in both hospitalizations and deaths due to COVID-19 in all age groups. We also estimated that vaccination prevented 170,959 hospitalizations (CI 95% 77,844–264,075) and 24,546 deaths (CI 95% 2,548–46,543) in Spain between March 2021 and December 2021. We estimated a global reduction of 9.19% in total deaths during the first year of COVID-19 vaccination. Conclusions: Demographic and clinical profiles changed over the first months of the pandemic. Patients over 80 years old and other age groups obtained clinical benefit from early vaccination. The severity of COVID-19, in terms of hospitalizations and deaths, decreased due to vaccination.

The effect of initial immunosuppressive therapy on the kinetics of the SARS-CoV-2 vaccine-induced humoral response is unknown. Here, we compared the kinetics of SARS-CoV-2 vaccine-induced humoral response in chronic kidney disease patients undergoing kidney transplantation (KTRs) and compared to patients remaining on dialysis during the Omicron circulation. This prospective, non-randomized, real-world study included 113 KTRs and 108 patients on dialysis. Those with previous COVID-19 or negative IgG at screening were excluded. Blood samples were collected to assess SARS-CoV-2 IgG titers and neutralizing antibodies at months (M) 1, 3, 6, and 12. Seroreversion occurred in 1 KTR and in 3 patients on dialysis. KTRs had lower IgG titers over time (M1: 10,809.3±12,621.7 vs. 15,267.8±16,096.2 IU/mL; M3: 12,215.5±12,885.8 vs. 15,016.2±15,346.1 IU/mL; M6: 12,540.4±13,010.7 vs. 18,503.5±14,581.0 IU/mL; p=0.005), but Neutralizing antibodies were similar (M1: 94.0 vs. 90.3%; M3: 92.9 vs. 90.5%; M6: 99.0 vs. 95.5%; M12: 98.9 vs. 97.5%; p=0.812). During follow-up, KTRs received more vaccine (141 vs. 73; p<0,001) and had more COVID-19 (32.7% vs. 14.8%; p=0.002). Compared to patients on dialysis, KTRs had lower SARS-CoV-2 IgG titers and similar rates of seroreversion and neutralizing antibodies over time. Although KTRs received more boosters, they had a higher incidence of COVID-19.

Emerging evidence suggests that patients suffering from COVID-19 may experience neurocognitive symptoms. Besides, other studies indicate a probable association between leukocyte telomere length (LTL) and neurocognitive changes in subjects with post-COVID-19 condition. Our study was designed to determine the correlation between telomere length and cognitive changes in subjects post-COVID-19. The study included 256 subjects, categorized based on SARS-CoV-2 infection from 2020 to 2023. On the other hand, those subjects who have a psychiatric diagnosis are considered. Besides, the MoCA and MMSE scales were applied. Telomere length was determined using a Polymerase Chain Reaction, and statistical analysis was employed ANOVA and X2 tests. We identified a decrease in LTL in individuals with post-COVID-19 conditions compared to those without SARS-CoV-2 infection (p≤0.05). However, no association was found between LTL and cognitive impairment in subjects post-COVID-19. The findings suggest that LTL is affected by SARS-CoV-2 infection. Nonetheless, this important finding requires further research by monitoring neurological changes in subjects with post-COVID condition.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has exposed the vulnerabilities and unpreparedness of the global healthcare system in dealing with emerging zoonoses. In the past two decades, coronaviruses (CoV) have been responsible for three major viral outbreaks, and the likelihood of future outbreaks caused by these viruses is high and nearly inevitable. Therefore, effective prophylactic universal vaccines targeting multiple circulating and emerging coronavirus strains are warranted. This study utilized an immunoinformatic approach to identify evolutionarily conserved CD4+ (HTL) and CD8+ (CTL) T cells, and B-cell epitopes in the coronaviral spike (S) glycoprotein. A total of 132 epitopes were identified, with the majority of them found conserved in the bat CoV, pangolins CoV, endemic coronaviruses, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Their peptide sequences were then aligned and assembled to identify the overlapping regions. Eventually, two major peptide assemblies were derived based on their promising immune-stimulating properties. In this light, they can serve as lead candidates for universal coronavirus vaccine development, particularly in the search for pan-coronavirus multi-epitope universal vaccines that can confer protection against current and novel coronaviruses.

Objectives: This study aimed to compare the similarities and differences between the Kawasaki disease (KD) during the SARS-CoV-2 pandemic and multisystem inflammatory syndrome in children (MIS-C). Methods: The medical records of patients diagnosed with KD and MIS-C at a single center between July 2020 and November 2021 were retrospectively reviewed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. Compared with the KD patients, MIS-C patients were older (p<0.001), had longer hospital stays (p=0.023), elevated neutrophil count (p<0.001), C-reactive protein (p<0.001), procalcitonin (p<0.001), interleukin-6 (p<0.014), ferritin (p<0.001), fibrinogen (p<0.001), troponin I (p=0.001), NT-proBNP (p<0.001), and, D-dimer levels (p<0.001). They had more hypotension (p=0.024), decreased left ventricular function (p=0.023), and a greater need for corticosteroids (p<0.001), enoxaparin (p=0.045), and therapeutic plasma exchange (p<0.001). Patients with KD displayed a higher frequency of rash (p<0.001), oral mucosal changes (p<0.001), conjunctival injection (p<0.001), extremity changes (p<0.001), and cervical lymphadenopathy (p<0.001). They had a longer duration of fever (p<0.001), elevated white blood cell count (p<0.001), platelet count (p<0.001), and alanine aminotransferase level (p<0.001). The two groups were similar in terms of hemoglobin levels, erythrocyte sedimentation rate, albumin levels, or the frequency of coronary dilation/aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Older patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas a longer duration of fever and classical clinical features of KD favor KD.

Background: It has shown that meal timing, poor sleep quality and chronotype could play a relevant role in the development of type 2 diabetes mellitus (T2DM). However, the relationship with macronutrients by eating occasions has not been explored deeply. Objective: Our aim was to estimate the association between chrono-nutrition, sleep quality, chronotype and the prevalence of T2DM. Methods: This cross-sectional study included a subset of 3465 middle-aged adults (2068 women) from the European Prospective Investigation into Cancer and Nutrition (EPIC) Spain cohort study. In the 2017-18 follow-up, we assessed chronotype, sleep quality, diet, and sociodemographic data by validated questionnaires. Further, we used blood samples to determinate serum levels of glucose. We defined a case of T2DM when serum glucose concentration was ≥126 mg/dl or when participants self-reported diabetes. Results: Higher prevalence of T2DM was associated with poor sleep quality (ORpoorvsgood=2.90, 95%CI=1.30, 6.28). Carbohydrate intake at breakfast was inversely associated with the prevalence of T2DM (OR=0.75, 95%CI=0.66, 0.85). Finally, lipid intake at breakfast were associated with a 13% higher the prevalence of T2DM (OR=1.13, 95%CI=1.01, 1.26) for each 1 standard deviation (1-SD) increase. We observed no associations between macronutrient intake at lunch or dinner and T2DM. Conclusions: The study concludes that a breakfast with higher content in carbohydrate at breakfast is correlated with a reduced prevalence of T2DM. While higher lipids intake at breakfast was associated with higher prevalence of T2DM. Furthermore, poor sleep quality is as a potential factor associated with an elevated prevalence of T2DM. Our results emphasize the need for prospective studies to validate and strengthen these observed associations.

Type 2 diabetes mellitus (T2DM) poses a significant economic and clinical burden. Clinical inertia is defined as the failure of healthcare providers to modify therapy in the presence of clear indications. This study aimed to identify patient opinions on insulin to understand the barriers preventing type 2 diabetes patients from initiating insulin treatment when recommended by their physician. This cross-sectional observational study included 671 individuals with poorly controlled T2DM and HbA1c levels exceeding 10%. These patients required either the initiation or escalation of their existing insulin therapy. The participants were referred to Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) for consultation between January 2022 and July 2022.Results: During discussions between the researcher (clinician) and the inadequately controlled T2DM patients, the primary reasons for refusing insulin therapy were identified. These reasons included fear of injections, the belief that insulin induces dependence and is a last resort, concerns about hypoglycemia and complications, cost, difficulty in computing doses, social stigma, inconvenience and disruption to life and work, storage challenges, fear of weight gain, dependence on others, and lack of confidence.The study concludes that the clinical barriers faced by individuals who refuse the initiation of insulin therapy are diverse. The most common belief among the patients was that insulin leads to dependence (38%), while the smallest percentage cited a lack of confidence in insulin as an effective treatment for lowering hyperglycemia.

Memory decline is considered a normal part of aging, while the relationship between melatonin deficiency and cognitive function is complex and not fully understood. The present study investigated the role of melatonin deficiency functioning as a hormone at different ages on working and short-term recognition and spatial memory in rats. An age-related decline in memory function was tested in the Y-maze, the object recognition test, and the radial arm maze. Aging was associated with reduced expression of brain-derived neurotrophic factor (BDNF) throughout the hippocampus, whereas pinealectomy exacerbated this process specifically in the CA3 region of 3- and 14-month-old rats. The region-specific reduced expression of the extracellular signal-regulated kinase (ERK)1/2 and pERK1/2 was observed in young adult rats with pinealectomy. However, in middle-aged rats, the expression of these signaling molecules was either downregulated or upregulated in different hippocampal regions. The reduced ratio of pCREB/CREB in the frontal cortex and hippocampus was associated with memory impairment in young adult and middle-aged melatonin-deficient rats, whereas old rats were unaffected. Our study provides insights into the molecular pathways involved in age-related memory changes associated with melatonin deficiency, highlighting the importance of the BDNF / ERK1/2 / CREB pathway in the hippocampus and suggesting a critical period for intervention.

The Coronavirus disease 2019 (COVID-19) pandemic has significantly affected older adults. Identifying host COVID-19 susceptibility genes in elderly populations remains a challenge. Here, we aimed to identify host genetic factors influencing susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We genotyped 12 single nucleotide polymorphisms (SNPs) previously associated with the innate immune response in a total of 97 elderly (age &gt;65 years) residents of three long-term care facilities located in the area of Barcelona, Spain. Individuals were PCR-tested during SARS-CoV-2 outbreaks between September and November 2020. SARS-CoV-2 PCR tests revealed infection in 81 residents. Importantly, the 16 uninfected residents remained SARS-CoV-2 seronegative until vaccination (January and February 2021). After adjusting for sex and age, we found that two SNPs were significantly associated with SARS-CoV-2 infection susceptibility: MMS19 nucleotide excision repair protein homolog (MMS19)/rs2236575 (p = 0.029) and interferon-induced helicase C domain-containing 1 (IFIH1)/rs1990760 (p = 0.034). No association with SARS-CoV-2 infection was found for the 10 additional genotyped SNPs, which included 4 SNPs on chromosome 12 in the gene encoding oligoadenylate synthetase (OAS). Our results indicate that MMS19 and IFIH1 genetic variants were associated with resistance to SARS-CoV-2 infection in a cohort of institutionalized seniors.

Neurofibromas, rare benign tumors of the peripheral nerve sheath, present diagnostic challenges, particularly in diabetic patients with toe ulcers. This case involves a 55-year-old female with type 2 diabetes mellitus who developed an enlarging ulcer on her right second toe. The initial evaluation suggested a diabetic ulcer; however, advanced imaging revealed a mass-like lesion. Partial excision and biopsy confirmed a neurofibroma with spindle cells within the myxoid stroma and S100 protein expression. One month later, total excision and Z-plasty reconstruction were performed under general anesthesia. The patient’s postoperative recovery was uneventful, and the patient was discharged without complications. Follow-up revealed successful healing with no recurrence or functional issues. This case highlights the importance of considering neurofibromas in the differential diagnosis of diabetic toe ulcers to avoid misdiagnosis and ensure appropriate management.

Wastewater-based surveillance has emerged as an important method for monitoring SARS-CoV-2. This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time PCR. Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and two sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

COVID-19 infection in high-risk populations is fatal and has a poor prognosis, necessitating a test to determine the protectiveness of immune response. Antibody testing is necessary to determine the body's immune response to COVID-19 infection and also vaccination strategies. Among the various methods available, chemiluminescent immunoassay (CLIA) test is more widely used and accessible to determine antibody levels. This study aimed to determine the protection level of S-RBD SARS-CoV-2 IgG using CLIA compared to Surrogate Virus Neutralization Test (SVNT). The population of this study comprised all healthcare professionals who experienced S-RBD SARS-CoV-2 IgG antibody level examinations. S-RBD SARS-CoV-2 IgG antibody levels were examined using CLIA and SVNT. The cut-off was determined using Receiver Operating Characteristic (ROC) curve and AUC (Area Under the Curve) measurements were evaluated. The result showed a strong positive correlation between S-RBD SARS-CoV-2 IgG CLIA and SVNT with a value of r=0.933 and p &lt;0.001. The value ≥37.29 BAU/mL was determined as the cut-off based on SVNT 30% inhibition level with sensitivity, specificity, positive, and negative predictive values of 96.5%, 90.9%, 96.5%, and 90.9%, respectively. A titer of antibodies greater than or equal to 37.29 BAU/mL with CLIA showed the presence of protective antibodies compared to SVNT.