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.

The emergence of SARS-CoV-2 mutations pose significant challenges to diagnostic tests as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had the limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using the LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman’s ρ = 0.968; P<0.0001). In conclusion, nsp10 is a suitable target for SARS-CoV-2 RT-PCR assay.

The host glycosylation mechanism synthesizes the carbohydrates of glycoproteins of viral envelopes. Due to the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene by some mammalian species, including humans (negative-CMAH), Neu5Gc is no longer synthesized. Uptake of Neu5Gc by negative-CMAH species, through the intake of food products derived from positive-CMAH mammals, leads to incorporating Neu5Gc-glycans in the glycocalyx (xenosialylation). Neu5Gc, being a Mammalian-associated Carbohydrate Antigen (MCA), acts as a non-self-antigen, inducing an inflammatory reaction (Xenosialitis), and triggering the production of circulating antiNeu5Gc antibodies to attack/remove all incorporated Neu5Gc. In the state of Xenosialitis, the virus-neutralizing antibodies produced by a heavily xenosialylated patient following exposure to viral infection (including SarsCoV2) or anti SarsCoV2 vaccination cross-react against all incorporated non-self Neu5Gc-MCA glycans due to their resemblance with viral envelope antigens synthesized by the host glycosylation mechanism. In addition, the circulating anti-XeSias antibodies determine the massive removal of the circulating neutralizing FC-xeno-contaminated antibodies by the serum, living only the hyper-inflammatory agalattosylated antiviral IgG antibodies. Therefore, we hypothesize that the combination of antibody cross-reaction against non-self Neu5Gc-MCA glycans and the massive removal of the xeno-contaminated newly formed neutralizing antibodies in favor of hyper reactive antibodies, could be the cause of the massive inflammatory reaction (cytokine storm, coagulopathies, neuropathies) observed in Covid 19 patients or after anti-SarsCoV2 vaccination. This analysis is an invitation to investigate the post-infectious and/or post-vaccination adverse phenomena in the light of xenosialization as a key to understanding the severe post viral and post vaccine complications, including SARS-CoV2 infection or related vaccination.

Background: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) affects human respiratory function causing COVID-19 disease. Safe natural products with potential antiviral phytochemicals with benefits to control high-altitude sickness could be adopted as adjunct therapy for COVID-19. The red petals of Rhododendron arboreum, commonly available and consumed in the Himalayan region may have phytochemicals with potential antiviral properties against COVID-19 targets.Purpose: This study was aimed to profile the secondary metabolites of R. arboreum petals, to assess their absorption, distribution, metabolism and elimination (ADME) properties and evaluate their antiviral potential by docking against COVID-19 targets such as SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin Converting Enzyme 2 (ACE2) receptor (PDB ID: 1R4L) that mediates the viral replication and entry into the host respectively.Methods: The phytochemicals of R. arboreum petals were mainly profiled using Gas Chromatography-Mass Spectroscopy (GC-MS) and ¹H-NMR. In addition, the phytochemicals reported from the literature were tabulated. The ADME properties of the phytochemicals were predicted using SwissADME tool. Molecular docking simulation of the phytochemicals against SARS-CoV-2 main protease (M^pro PDB ID: 6LU7) and Human Angiotensin converting enzyme 2 (ACE2) receptor (PDB ID: 1R4L) were carried out using PyRx.Results: R. arboreum petals were found to be rich in appreciable proportions of secondary metabolites such as Quinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, 5-O-Feruloylquinic acid, 2,4-Quinolinediamine, Coumaric acid, Caffeic acid, Epicatechin, Catechin, 3-Hydroxybenzoic acid, Shikimic acid, Protocatechuic acid, Epicatechin gallate, Quercetin, Quercetin-O-pentoside, Quercetin-O-rhamnoside, Kaempferol-O-pentoside and Kaempferol. Several of these phytochemicals were reported to exhibit inhibitory activities against a range of viruses. From the molecular docking studies, 5-O-Feruloylquinic acid, 3-Caffeoyl-quinic acid, 5-O-Coumaroyl-D-quinic acid, Epicatechin and Catechin showed strong binding affinity with SARS-CoV-2 M^pro and human ACE2 receptor.Conclusion: This report showed that R. arboreum petals are rich in several antiviral phytochemicals that also docked against SARS-CoV-2 M^Pro and Human ACE2 receptor. This is the first report highlighting R. arboreum petals as a reservoir of antiviral phytochemicals with potential for synergetic activities. The outcomes merit further in vitro, in vivo and clinical studies on R. arboreum phytochemicals to develop natural formulations against COVID-19 disease for therapeutic benefits.

In Wuhan city of China, an episode of novel coronavirus (COVID-19) happened. during late December and it has quickly spread to all places in the world. Until May 29, 2020, cases were high in the USA with 1.7 Million, Russia with approximately 387 thousand, the UK with 271 thousand confirmed cases. Everybody on the planet is anxious to know when the coronavirus pandemic will end. In this scourge, most nations force extreme medication measures to contain the spread of COVID-19. Modeling has been utilized broadly by every national government and the World Health Organization in choosing the best procedures to seek after in relieving the impacts of COVID-19. Many epidemiological models are studied to understand the spread of the illness and its prediction to find maximum capacity for human-to-human transmission so that control techniques can be adopted. Also, arrangements for the medical facilities required such as hospital beds and medical supplies can be made in advance. Many models are used to anticipate the results keeping in view the present scenario. There is an urgent need to study the various models and their impacts. In this study, we present a systematic literature review on epidemiological models for the outbreak of novel coronavirus in India. The epidemiological dynamics of COVID-19 is also studied. Here, In addition, an attempt to take out the results from the exploration and comparing it with the real data. The study helps to choose the models that are progressive and dependable to predict and give legitimate methods for various strategies.

The COVID 19 pandemic saw the emergence of various Variants of Concern (VOCs) that took the world by storm, often replacing the ones that preceded them. The characteristic mutant constellations of these VOCs increased viral transmissibility and infectivity. Their origin and evolution remain puzzling. With the help of data mining efforts and the GISAID database, a chronology of 22 haplotypes described viral evolution up until July 23, 2023. Since the 3-dimensional atomic structures of proteins corresponding to the identified haplotypes are not available, ab initio methods were here utilized. Regions of intrinsic disorder proved to be important for viral evolution, as evidenced by the targeted change to the nucleocapsid (N) protein at the sequence, structure, and biochemical levels. The linker region of the N-protein, which binds to the RNA genome and self-oligomerizes for efficient genome packaging, was greatly impacted by mutations throughout the pandemic, followed by changes in structure and intrinsic disorder. Remarkably, VOC constellations acted cooperatively to balance the more extreme effects of individual haplotypes. Our strategy of mapping the dynamic evolutionary landscape of genetically linked mutations to the N-protein structure demonstrates the utility of ab initio modeling and deep learning tools for therapeutic intervention.

Pneumonia cases of unknown etiology in Wuhan, China, were reported to the WHO on 31st of December 2019. Later the pathogen was reported to be a novel coronavirus designated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is a novel pathogenic beta coronavirus that infects humans causing severe respiratory illness. However, multifarious factors can contribute to the susceptibility to COVID-19 related morbidity and mortality such as age, gender and underlying comorbidities. Importantly, SARS-CoV and SARS-CoV-2 entry into the host cells is mediated via ACE2 receptor. However, ACE2 receptor binding affinity to SARS-CoV-2 is 4 folds higher than that to SARS-CoV. Identification of different aspects such as binding affinity, differential antigenic profiles of spike glycoproteins, and ACE2 polymorphisms might influence the investigation of potential therapeutic strategies targeting SARS-CoV-2/ACE2 binding interface. Here we aim to elaborate on SARS-CoV-2 S1/ACE2 ligand that facilitates viral internalization as well as to highlight the differences between SARS-CoVs binding affinity to ACE2. We also discuss the possible immunogenic sequences of spike glycoprotein and the effect of ACE2 polymorphism on viral binding/infectivity and host susceptibility to disease. Furthermore, targeting of ACE2 will be discussed to understand its role in therapeutics.

Conservation history of D614 residue is valuable in predicting the consequences of D614G mutation in the SARS-CoV-2 spike glycoprotein (SGP). We report here that the D614 belonged to an extraordinarily conserved, densely hydrophobic eleven amino acid peptide-motif vavlyqdvnct (11-aa), in the Sarbecovirus group and the variant carrying vavlyqdvnct had appeared in Chinese samples and became predominant in several geographical hotspots in late March, 2020. Interestingly a 2009 annotation of SARS-CoV contained the same mutation.

At a time when the world faces an emotional breakdown, crushing our dreams if not taking our lives, we realize that together we must fight the war against the COVID-19 outbreak even if almost the majority of the scientific community finds itself confined to home. Every day, like everyone else, we, scientists, listen to the latest news with its promises and announcements. Across the world, a surge of clinical trials trying to cure or slow down the coronavirus pandemic has been launched to bring hope instead of fear and despair. One first proposed clinical trial has drawn worldwide hype to the benefit of chloroquine (CQ), a well-known and broadly used anti-malarial drug, in the treatment of patients infected by the recently emerged deadly coronavirus (SARS-CoV-2). We should consider this information in the light of the long-standing anti-inflammatory and anti-viral properties of CQ-related drugs. Yet, none of the articles promoting the use of CQ in the current pandemic evoked a possible molecular or cellular mechanism of action that could account for any efficacy. Here, given the interaction of viruses with macroautophagy (hereafter referred to as autophagy), a CQ-sensitive anti-viral safeguard pathway, we would like to discuss the pros, but also the cons concerning the current therapeutic options targeting this process.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

To date, the impact of COVID-19 vaccination on formerly menstruating women remains unknown. For this reason, a retrospective observational cross-sectional study was conducted (N= 548) using an online survey. General characteristics, medical history, and adverse events following COVID-19 vaccination were recorded. In comparison with the first dose, significantly higher percentages of respondents experienced menstrual-related disturbances (dose 1: 38.5% vs. dose 2: 44.8%; McNemar=9.15; mid P-value=0.002), as well as the simultaneous occurrence of two or more of these symptoms (dose 1: 11.2% vs. dose 2: 15.3%; McNemar=13.53; mid P-value=0.044) after receiving the second one. Among them, those related with the length and flow stand out, being of long-term nature in about 17-20% of cases. Interindividual factors influencing this unexpected event after receiving the dose 1 may include weight (AOR 1.02, CI 95% 1.01–1.03, P&lt;.001), perimenopause (AOR 2.28, CI 95% 1.37–3.77, P=.001), pre-existing diagnoses of non-autoimmune rheumatic/articular conditions (AOR 0.31, CI 95% 0.10–1.00, P=0.05), hormonal contraceptive use (AOR 0.25, CI 95% 0.07-0.82, P=0.02), suffering from other vaccine side effects − such as arm pain (AOR 0.61, CI 95% 0.39–0.95, P=0.03), headache (AOR 0.53, CI 95% 0.35 – 0.80, P=.003), swollen glands (AOR 0.29, CI 95% 0.15 – 0.60, P=.001) and nauseas (AOR 0.35, CI 95% 0.14 – 0.86, P=0.02) – and the number of previous pregnancies (AOR 2.70, CI 95% 1.54 – 4.76, P=.001). Formerly menstruating women may experience long-term menstrual-related disturbances following COVID-19 vaccination.

The global pandemic caused by the new SARS-COV-2 coronavirus makes it necessary to search for drugs for its control. Within of this research it has been known that the ivermectin drug, a FDA-approved drugs which is formulated as an 80:20 mixture of ivermectin B1a and B1b and used commonly for parasitic infections, has an inhibitory effect on viruses, includes SARS-COV-2 at in vitro level. In the particular case of SARS-COV-2 its mechanism of action remains elusive and controversial. Interestingly, the energy of interaction of ivermectin with any of the proteins the SARS-CoV-2 and the possible structural alterations at the protein level that this drug can cause have not been reported. In this sense, we carried out a bioinformatics study with docking strategies and molecular dynamics to predict the binding and disturbance induced by ivermectin in proteins associated with SARS-CoV-2. We use DockThor and Molegro docking scores. The DockThor server and myPresto software were used to build complexes and dynamics studies, respectively. The results obtained suggested that ivermectin is capable of docking with the 3CL protease and the HR2 domain, and may promote structural changes in these proteins by inducing unfolding/folding. Specifically, ivermectin brings protease to a significantly more deployed conformational state and the HR2 domain to a more compact state compared to the native state. Finally, it is shown that B1a and B1b macrocyclic lactones have a behavior different from to each target protein. These results suggest a possible inhibitory effect against SARS-CoV-2 due to a synergistic role of this drug to spontaneously bind to two important proteins involve in the proliferation of this virus. However, more studies are required on this possible mechanism of action.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

A sense of crisis pervaded the university sector as Covid-19 spread, with worries about possible significant loss of income and students in its wake. This analysis examines several years of financial and student data through the pandemic (2020-2022) for Scottish universities. It shows that far from losing money or students, universities in Scotland gained both, and accelerated income growth during Covid. The University of Glasgow stands out not only among Scottish universities but also in the Russell Group in increasing income and student numbers faster than other institutions, becoming over the course of the pandemic, the third largest university in the UK and the largest in Scotland by student numbers. The driver of income growth for all Scottish universities is expanded intakes of international students, who primarily come from Asia and Africa. Across 2021 and 2022, Scottish Universities earned income totalling £1.7 billion from international tuition fee alone. Universities across the UK are increasingly dependent on yet continuing to actively pursue international tuition fees as a primary source of income. This paper documents the situation for Scotland, considering the implications of this growth trajectory in terms of: concentrating financial dependence on a single income source; rising casualisation of staff as a means of managing higher student numbers; impacts on learning and working conditions as students numbers rapidly expand; a shifting composition of students in higher education. It concludes with reflections on: a blurring boundary between the practices and values of profit-making companies and those of the charitable university sector; the ethical and colonial implications in international student recruitment and targeting of ‘new markets’ in the Global South; and the implications of all this for the shape, health and purpose of the university sector in Scotland.

The outbreak of COVID-19 has brought unprecedented risks and challenges to everyone in the world. Myasthenia gravis is an autoimmune disease of the nervous system. Infection can worsen it and cause severe symptoms such as myasthenia crisis and respiratory failure. At present, the pandemic of COVID-19 may promote the aggravation of patients with MG. This article focuses on the respiratory management of MG patients during the epidemic of COVID-19.

COVID-19 is an infectious disease, growth of which depends upon the linked stages of the epidemic, the average number of people one person can infect and the time it takes for those people to become infectious themselves. We have studied the COVID-19 time series to understand the growth behaviour of COVID-19 cases series. A structural break occurs in the COVID-19 series at the change time form one stage to another. We have performed the structural break analysis of data available for 207 countries till April 20, 2020. There are 42 countries which have recorded five breaks in COVID cases series. This means that these countries are in the sixth stage of growth transmission and show a downward pattern in reporting in the daily cases, whereas countries with two and three breaks, record the rapid growth pattern in the daily cases. From this study, we conclude that the more the breaks in the series, there is more possibility to determine the constant or decreasing rate of daily cases. It is well fitted using lognormal distribution as this distribution is archived at its highest peak after some period and then suddenly it decreases at a longer time period. This can be seen in various countries like China, Australia, New Zealand and so on.

Corona Virus Infectious Disease-2019 (COVID-19) outbreak originated recently at Wuhan, China in December 2019. It has already spread rapidly to more than 200 countries and has been declared a pandemic by WHO. It is caused by a beta-coronavirus named as SARS-CoV-2. There is no definitive cure, either drug or vaccine, to treat or prevent this viral disease. Recently, the crystal structure of the main protease M^pro has been determined. M^pro is responsible for the proteolytic maturation of the polyprotein essential for the viral replication and transcription, which makes it an important drug target. The discovery of new drug molecules may take years before getting to the clinics. So, considering urgency we performed molecular docking studies using FDA approved drugs to identify molecules that could potentially bind to the substrate-binding site and inhibit SARS-CoV-2 main protease (M^pro). We used the Glide module in Schrodinger software suite to perform molecular docking studies followed by MM-GBSA based energy calculations to score the hit molecules. Molecular docking and manual analysis suggest that several drugs may bind and potentially inhibit M^pro. We also performed molecular simulations studies for selected compounds to evaluate protein-drug interactions. Interestingly, we observed only one antiviral compound, Adefovir, in the top50 list of compounds. Considering bioavailability, lesser toxicity, route of administration some of the top-ranked drugs including lumefantrine (antimalarial), dipyridamole (coronary vasodilator), dihydroergotamine (used for treating migraine), hexoprenaline (anti- asthmatic), riboflavin (vitamin B2) and pantethine (vitamin B5) may be taken forward for further in vitro and in vivo experiments to investigate their therapeutic potential.

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track virus genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be 18 September 2021 (95% highest posterior density (HPD) 04 August – 22 October 2021) and 1.435×10-3 (95% HPD = 1.021×10-3 – 1.869×10-3) substitution/site/year, respectively, whereas 03 November 2021 (95% highest posterior density (HPD) 26 September – 28 November 2021) and 1.074×10-3 (95% HPD = 6.444×10-4 – 1.586×10-3) substitution/site/year for BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study shed light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics the virus and, as a result, mitigate the impact of emerging variants on public health.

To assess if SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint able to be used in the non-invasive COVID-19 diagnosis and management, urine samples of SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41) were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). In total, 101 volatile organic metabolites (VOMs) from 13 chemical families were identified, being terpenes, phenolic compounds, norisoprenoids, and ketones the most represented groups. Overall, a decrease in the levels of terpenes and phenolic compounds was observed in the control group, whereas norisoprenoids and ketones showed a significant increase. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID-19 group. Multivariate statistical analysis identified sets of VOMs with the potential to constitute volatile signatures for COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. This study provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist, of which Middle East Respiratory Syndrome (MERS) and SARS-CoV (SARS) showed higher mortality rates without causing a pandemic. As of December 2022, SARS-CoV-2 has resulted in over 6.6 million deaths worldwide through an array of acute to chronic pathologies. Historical pandemics include smallpox and influenza with efficacious therapeutics utilized to reduce overall disease burden. Therefore, immune system process analysis is required to compare innate and adaptive immune system interactions. Lymphatic system organs include bone marrow and thymus using a network of nodes throughout which white blood cells traverse glycolipid membranes utilizing cytokines and chemokine gradients that affect cell development, differentiation, proliferation, and migration processes as well as genetic factors affecting cell receptor expression. Innate processes involve antigen-presenting cells and B lymphocyte cellular responses to pathogens relevant to other viral and bacterial infections but also in oncogenic diseases. Such processes utilize cluster of differentiation (CD) marker expression, major histocompatibility complexes (MHC), pleiotropic interleukins (IL) and chemokines. The adaptive immune system consists of Natural Killer (NK) and T cells. Other viruses are also contributory to cancer including human papillomavirus (cervical carcinoma ), Epstein-Barr virus (EBV) ( lymphoma), hepatitis B and C (hepatocellular carcinoma) and human T cell leukemia virus-1 (adult T-cell leukemia). Bacterial infections also increase the risk of developing cancer( e.g. H. pylori). Therefore, as the above factors can cause both morbidity and mortality along-side being transmitted within clinical and community settings, it is appropriate to now examine advances in single cell sequencing, FACS analysis and many other laboratory techniques that allow insights into discoveries of newer cell types. These developments offer improved clarity and understanding that over-lap with known autoimmune conditions that could be affected by innate B cell or T cell responses to SARS-CoV-2 infection. Thus, this review quantifies and outlines the nature of specific receptors and proteins relevant to clinical laboratories and medical research by documenting both innate and adaptive immune system cells within current coronavirus immunology case study data and other pathologies to date.

Objectives: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. Methods: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. Results: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVIS-19 patients have both central memory TCD8+ T cells and activated effector TCD8+ cells. Non-severe COVID-19 cases showed an increase in IL1β, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8.Conclusion: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is sufficient experimental evidence to confirm that SARS-CoV-2 infection produces states of ciliary and flagellar dysfunction. However, these studies are unable to explain the observed effects molecularly, because they lack a sufficient understanding of the interaction between human proteins and virus proteins. Using the physical-chemical study of the human interactome in interaction with the SARS-CoV-2 proteome, we found evidence of interactions to explain the experimental effects from a molecular perspective. We found that ten viral proteins interact with key components in the maintenance of the molecular structure of axoneme. Additionally, we evaluated the pulmonary and extrapulmonary pathogenesis of COVID-19 from the point of view of ciliary dysfunction, and warned about other possible complications such as episodes of transient infertility that, due to the limitations of our work, would need verification.

Coronavirus disease 2019 (COVID-19) since its declaration as a pandemic by world health organization (WHO) has spread across the various continent with little known about the most effective public health response for containing and mitigating the transmission of the epidemic. It is important to state that some authors have published on the lessons learned from transmission and management of COVID-19 infection but only a few considered it from the Africa perspective. Despite the late arrival of the pandemic in Africa and the notion that the virus may not thrive because of the high temperature in the continent; today the narrative has changed with the number of infected patients increasing daily. Herein, the authors have shared their perspectives and opinions on the dynamics and response to COVID-19 from Africa context to create more awareness and approach in mitigating the spread of the virus should the continent becomes the epicenter of COVID-19.

The study investigated the application of Wastewater-Based Epidemiology (WBE) as a tool for monitoring SARS-CoV-2 prevalence in a city in Northern Italy from October 2021 to May 2023. Starting from a widely applied deterministic model, this study proposed a variation to take into account population characteristics and virus biodegradation in the sewer network. The model calculated virus loads and corresponding COVID-19 cases over time in different areas of the city and was validated with healthcare data while considering viral mutations, vaccinations, and testing variability. The correlation between the predicted and reported cases was high across the three waves that occurred in the considered period, demonstrating the model’s capacity to predict relevant fluctuations in the number of cases. Population characteristics did not substantially influence the predicted and reported infection rates. Conversely, biodegradation significantly reduced the virus load reaching the wastewater treatment plant, resulting in a 30% reduction in the total virus load produced in the study area. This approach can be applied for comparing virus load values across cities with varying population demographics and sewer network structures, enhancing the comparability of WBE data for effective surveillance and intervention strategies.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

A growing number of studies suggest that SARS-CoV-2 could interfere with homeostatic mechanisms in the lung but the implications of this possible interference have not been fully explored in the literature. In this work, we examine the consequences that can be drawn from this hypothesis according to currently available knowledge. We suggest that one such consequence is the potential disruption of normal ventilation and perfusion of lung regions that may be distant from the infection sites. Loss of ventilation might result in local alveolar hypoxia and contribute to hypoxemia, which in turn could trigger homeostatic responses that enhance blood oxygenation by redistributing pulmonary blood circulation. Sudden changes in perfusion might then lead to the development of hydrostatic edema and eventually to vascular remodeling and inflammation. Therefore, the immune response might not be the only source of the substantial inflammation observed in lung tissues of patients with severe COVID-19, as is often assumed in the literature. The balance between the homeostatic and the immune reaction in each patient could account for the observed heterogeneity of the clinical manifestations of COVID-19.

Emerging information on the interactions between the COVID-19 pandemic and global food systems has highlighted how the pandemic is accentuating food crises across Africa. Less clear, however, are how the impacts differ between farming systems. Drawing on 50 key informant interviews with farmers, village leaders and extension officers, in South Africa and Tanzania, we identify the effects of COVID-19 and associated measures to curb the spread of the disease on farming production systems, the coping mechanisms adopted by farmers, and explore their longer-term plans for adaptation. We focus on a diverse range of production systems, from small-scale mixed farming systems in Tanzania, to large-scale corporate farms in South Africa. Our findings highlight how COVID-19 restrictions have interrupted the supply chains of agricultural inputs and commodities, increasing the storage time for produce, decreasing income and purchasing power, and reducing labour availability. Farmers’ responses were heterogeneous, with highly diverse small-scale farming systems and those less engaged with international markets least affected by the associated COVID-19 measures. Large-scale farmers were most able to access capital to buffer short-term impacts, whereas smaller-scale farms shared labour, diversified to subsistence produce and sold assets. However, compounded shocks, such as recent extreme climate events, limited the available coping options, particularly for smaller-scale and emerging farmers. The study highlights the need to understand the characteristics of farm systems to better equip and support farmers, particularly in contexts of uncertainty. We propose that policy actions should focus on (i) providing temporary relief and social support and protection to financially vulnerable stakeholders, (ii) job assurance for farmworkers, and engaging an alternative workforce in farming, (iii) investing in farming infrastructure, such as storage facilities, digital communication tools, and extension services, and iv) supporting diversified agroecological farming systems.

Objectives: This paper presents a statistical review of modelling simulations for frequency and sensitivity of COVID-19 testing paradigms. Methods: We performed a review of preprints and published articles on PubMed from January 1, 2020 – March 1, 2021 using the search terms “COVID screening testing”, “COVID testing frequency”, “COVID testing frequency screening” and “SARS-CoV-2 testing frequency”.Results: Several authors’ conclusions support the claim that test frequency and test sensitivity both play a role in reducing SARS-CoV-2 transmission. We highlight the interplay between frequency of testing, test sensitivity and the speed at which test results are available in our review. Conclusions: Evidence suggests that sensitivity and frequency of testing both play a part in decreasing transmission of disease. We conclude that, overall, test sensitivity plays less of a role in reducing disease transmission in a population compared to the frequency of testing and how quickly test results are available.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19. There are good reasons to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID- 19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background of this hypothesis based on lungs and intestine relationships.

Coronaviruse disease (COVID-19) outbreak has created an emergency globally, and social distancing and isolation is the only solution to prevent its spread. Several countries have announced fully locked on to tackle this pandemic. The recent COVID-2019 has shaken the globe with incidence cases of more than half-million cases, and a mortality toll of more than twenty thousand to date. The coronavirus family is inclusive of pathogen of both – animal species and humans, encapsulating the isolated severe acute respiratory syndrome coronavirus (SARS-CoV). Researchers round the globe have been dexterously working to decode this lethal virus. Many mathematical frameworks have also been depicted which have helped to understand the dynamics of the COVID-19. Research on coronaviruses continues to explore various aspects of viral replication and pathogenesis to understanding the predilection of these viruses to switch between species, to develop an infection in a new host, and to identify significant reservoirs of coronaviruses will dramatically aid in our potential to prophesize when and where potential epidemics may occur. Many of the non-structural and accessory proteins encoded by the viruses remain unclear and unknown. This systematic review highlights the current situation of the pandemic, virus genomic composition, pathogenesis, symptomatology, diagnosis, and prognosis along with mathematical models of disease transmission and dynamics.

At-home rapid antigen test (RAT) kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are valuable public health tools during the present coronavirus disease (COVID-19) pandemic. They provide fast identification of coronavirus infection, which can help to reduce the transmission rates and burden on the healthcare system. However, they have lower sensitivity when compared with the reverse transcription polymerase chain reaction (RT-PCR) tests. One of the reasons for the lower sensitivity is due to the RAT color indicators being indistinct or invisible to the naked eye after the measurements. For this reason, we propose a systematic approach, through which we investigated anonymously provided at-home RAT kit results by using our in-house open source image processing scripts developed for affordable Raspberry Pi computer and Raspberry Pi HQ camera systems (available at https://github.com/kmiikki/ratcv). Therefore, we aimed at minimizing the human-related analysis errors for such kits. We believe that our framework can contribute to reduced the delayed quarantines of infected individuals and spreading of the current infectious disease.

SARS-CoV-2 virus infections in humans were first reported in December 2019, the boreal winter. The resulting COVID-19 pandemic was declared by the WHO in March 2020. By July 2020 COVID-19 is present in 213 countries and territories, with over 12 million confirmed cases and over half a million attributed deaths. Knowledge of other viral respiratory diseases suggests that the transmission of SARS-CoV-2 could be modulated by seasonally-varying environmental factors such as temperature and humidity. Many studies on the environmental sensitivity of COVID-19 are appearing online, and some have been published in peer-reviewed journals. Initially, these studies raised the hypothesis that climatic conditions would subdue the viral transmission rate in places entering the boreal summer and that southern hemisphere countries would experience enhanced disease. For the latter, the COVID-19 peak would coincide with the peak of the influenza season, increasing misdiagnosis and placing an additional burden on health systems. In this review, we assess the evidence that environmental drivers are a significant factor in the trajectory of the COVID-19 pandemic, globally and regionally. We critically assessed 42 peer-reviewed and 80 preprint publications that met qualifying criteria. Since the disease has been prevalent for only half a year in the northern, and a quarter of a year in the southern hemisphere, datasets capturing a full seasonal cycle in one locality are not yet available. Analyses based on space-for-time substitutions, i.e. using data from climatically distinct locations as a surrogate for seasonal progression, have been inconclusive. The reported studies present a strong northern bias. Socio-economic conditions peculiar to the ‘Global South’ have been omitted as confounding variables, thereby weakening evidence of environmental signals. We explore why research to date has failed to show convincing evidence for environmental modulation of COVID-19, and discuss directions for future research. We conclude that the evidence thus far suggests a weak modulation effect, currently overwhelmed by the scale and rate of the spread of COVID-19. Seasonally-modulated transmission, if it exists, will be more evident in 2021 and subsequent years.

Before December 2020, Antarctica had remained free of Covid-19 cases. The main concern during the pandemic was the limited health facilities available at Antarctic stations to deal with the disease, as well as the potential impact of SARS-CoV-2 on Antarctic wildlife through reverse zoonosis. In December 2020, 60 cases emerged in Chilean Antarctic stations, disrupting the summer campaign with ongoing isolation needs. The SARS-CoV-2 RNA was detected in the wastewater of several scientific stations. In Antarctica, treated wastewater is discharged directly into the seawater. No studies currently address recovery of infectious virus particles from treated wastewater, but their presence raises the risk of infecting wildlife and initiating new replication cycles. This study highlights the initial virus detection in wastewater from Antarctic stations, identifying viral RNA via RT-qPCR targeting various genomic regions. The virus's RNA was found in effluent from two wastewater plants at Maxwell Bay and O’Higgins Station on King George Island and the Antarctic Peninsula, respectively. This study explores the potential for reverse zoonotic transmission of SARS-CoV-2 from humans to Antarctic wildlife due to the direct release of viral particles into seawater. The implications of such transmission underscore the need for continued vigilance and research.

Background: Comorbidities have been frequently reported in COVID-19 patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 receptor and host proteases, namely FURIN and TMPRSS2 that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia (hereafter, referred as leukemia). The expression of ACE2 was also increased in psoriasis, lung cancer, Non-alcoholic fatty liver disease (NAFLD), breast cancer, and pulmonary arterial hypertension patients. The expression of FURIN was higher in psoriasis, NAFLD, lung cancer, and in type II diabetic liver, whereas it was lowered in breast cancer. Similarly, the expression of TMPRSS2 was increased during lung cancer and type II diabetes; it was decreased during psoriasis, NAFLD, lung cancer, breast cancer, and cervical cancer.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia patients, as shown by the higher expression of IFNA2, IFNA8, IFNA10, IFNA14, IFNA16, IFNA21, IFNB1, CXCL10, and IL6. The expression of JAK1, STAT1, IL6, and CXCL10 was higher in NAFLD. Besides, JAK1 and STAT1 were upregulated in type II diabetic muscles. In addition, most of the upregulated genes in COVID-19 patients showed a similar trend in leukemia, NAFLD, and psoriasis. Furthermore, SARS-CoV-2, SARS-CoV and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection are mostly upregulated in leukemia patients; hence, leukemia patients are relatively more susceptible to develop COVID-19, followed by other chronic disorders, such as, NAFLD, type II diabetes, psoriasis, and hypertension. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 and underlie COVID-19 associated comorbidities.

When it is in the template RNA, the naturally occurring m¹A epitranscriptomic RNA modification was recently reported to be able to stop the RNA polymerization reaction catalyzed by the RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. In this report, we report that m¹A via its triphosphate form (m¹ATP) can be incorporated into RNA by the same RdRp. These two findings point a new direction for antiviral drug development based on m¹A for combatting COVID-19. More broadly, it is possible that the large pool of epigenetic RNA as well as DNA modifications could serve as a treasury for drug discovery aimed at combating various infectious and other diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an outbreak of COVID-19 disease in humans with the aid of spike protein. It consists of a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2). The aim of this study was to examine the mutational effect of spike protein on the sequence through an interaction study of the mutant spike protein and the human ACE2 protein at the structural level. A total of 17,227 spike proteins from Asia, Africa, Europe, Oceania, South America, and North America were compared to the Wuhan spike protein reference sequence (Wuhan-Hu-1). The structural and stability implications of D614G, N501Y, and S477N mutations were evaluated. The binding affinity between mutated RBD and human ACE2 protein was also studied. The D614G mutation may have originated in Germany, Europe based on the date of the first sample collection report. It is now widely circulated all over the world with most occurrences in North America. The mutations N501Y and S477N may have originated from Oceania based on the date of the first sample collection report and also have the highest occurrences in Oceania. Based on the computational analysis of mutational effects, the D614G, N501Y, and S477N mutations decreased stability and were tolerated. For disease propensity prediction, N501Y was more prone to disease compared to D614G, while S477N was not prone to disease. The mutation of D to G at position 614 and S to N at position 477 for secondary structure prediction shows no changes in secondary structure while remaining in the coil region, whereas the mutation of N to Y at position 501 changes from coil structure to extended strand. N501Y mutation has a higher affinity to human ACE2 protein compared to D614G and S477N based on a docking study. D614G spike mutation was identified to exist between the two hosts based on a comparison of SARS-CoV-2 derived between the mink and human. Further research is needed on the link between the mink mutation N501T and the mutation N501Y in humans, which has evolved as a separate variant.

In December 2019, an animal human coronavirus transmission occurred in Wuhan, China. A state of global pandemic was shortly declared, among a very rapid contagious spread of the virus. The causative virus was identified as SARS CoV 2 virus and is genetically related to the previous SARS outbreak in 2003. The virus causes wide clinical spectrum from mild flu like symptoms to adult respiratory distress syndrome. Kidney involvement has been reported in several reports in patients with various degrees of severity of SARS CoV2 infection. As knowledge is evolving, the accurate incidence of AKI is not known. Many questions are yet to be answered as regards the effect of epidemiological variables and comorbidities on the occurrence of AKI. Some reports have observed the occurrence of hematuria and proteinuria in a percentage of infected patients. Moreover, chronic kidney disease has not been found in some reports to add to the adverse outcomes, an aspect that merits further exploration. Patients on regular hemodialysis may be vulnerable to contagion due to lower status of immunity and need for frequent attendance to healthcare facilities. Due to the previous factors, prevention and mitigation of SARS CoV2 virus in this vulnerable population constitutes a major challenge.

This article investigated whether the atmospheric temperature had any role in the spread and vulnerability to COVID-19 worldwide and how that knowledge can be utilized to contain the fast-spreading disease. It highlighted that temperature was an important factor in transmitting the virus, and a moderately cool environment was the most favourable state for its susceptibility. In fact, the risk from the virus is reduced significantly in high temperature environment. Warm countries and places were likely to be less vulnerable. We identified various degrees of vulnerability based on temperature and specified countries for March and April. The maximum reported case, as well as death, was noted when the temperature was in the range of around 275°K (2°C) to 290°K (17°C). Countries like the USA, UK, Italy and Spain belonged to this category. The vulnerability was moderate when the temperature was less than around 275°K (2°C) and countries in that category were Russia, parts of Canada and few Scandinavian countries. For temperature 300°K (27°C) and above, a significantly lesser degree of vulnerability was noted. Countries from SAARC, South East Asia, the African continent and Australia fell in that category. In fact, when the temperature was more than 305°K (32°C), there was a unusually low number of reported cases and deaths. For warm countries, further analyses on the degree of vulnerability were conducted for the group of countries from SAARC and South East Asia and individual countries were compared. We also showed countries can switch from one vulnerability state to another based on the variability of temperature. We provided maps of temperature to identify countries of different vulnerability states in different months of the year. That influence of temperature on the virus and previous results of clinical trials with similar viruses gave us a useful insight that regulating the level of temperature can provide remarkable results to arrest and stop the outbreak. Based on that knowledge, some urgent solutions are proposed, which are practically without side effects and very cost-effective too.

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro by protein chemical methods, mass-spectrometry, circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in large amounts as secreted and folded proteins in mammalian cells. Antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG levels induced by the different vaccines were comparable but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were 7- and 2-fold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively and 6-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

The Coronavirus pandemic is a major challenge to human wellbeing; it directly affects health, and indirectly involves the economic, politic and social spheres. This, in turn, is going to have major systemic, worldwide health, social and environmental consequences. In this paper, I will briefly sum up the history of the pandemic, the worldwide diffusion, the major different political reactions, as well as health and political countermeasures, and the economic consequences / evaluations for the future. The aim of this paper is to show and address all the different spheres involved and their relationships. Emphasis will be placed on the paradoxical presence of a large amount of data and the big uncertainty for the future. The outcomes will be briefly analyzed on a healthcare, political and socio-economical level. The point of view is systemic with human beings, institutions and the environment seen as a whole. Systemic thinking allows interdisciplinary research to be decisive in understanding the worldwide reaction to the pandemic. The global response to this crisis is of historical significance, and therefore potentially decisive for the multi-layered future of the world.

The goal of this study is to develop a global analysis, based on data from 2015 to 2022, that clarifies the impact of containment policies (e.g., lockdown and quarantine) for Coronavirus Disease-2019 (COVID-19) on the air pollution between countries of different continents. In this context, average changes of CO, NO2, SO2, O3, PM2.5, and PM10 concentrations based on measurements at ground level in January, February, and March for 2019, 2020, 2021, and 2022 are compared with average values of 2015-2018 period between 300 cities of 19 countries in 5 continents. Results show that the maximum reduction in pollutant concentrations during this period is given by: CO (-4,367.5%) in France, NO2 (-150.5%) in China and Australia, SO2 (-154.1%) in Israel, O3 (-94.1%) in China, PM2.5 (-41.4%) in Germany and PM10 (-157.4%) in Turkey. Findings reveal that the effects of containment policies on air quality vary significantly between countries depending on different geographical characteristics of regions. This study has main environmental policy implications because it clarifies the critical role of severe control measure to reduce air pollution and support sustainable environment and development.

The current emergency due to the worldwide spread of the COVID-19 caused by the new SARS-CoV-2 is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness was not yet assessed. The main protease (Mpro) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent Mpro inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed to highlight some crucial aspects. Seventeen potential SARS-CoV-2 Mpro inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.

Purpose: The healthcare pressure and emotional tension during the first year of the COVID 19 pandemic have been able to affect the health of healthcare personnel. Physical and psychological symptoms attributed to a work situation and or COVID 19 infection are describ ed in health professionals. Objective: to analyze the prevalence of physical and psychological symptoms directly or indirectly related to COVID 19 (occupational causes, illness or persistent COVID 19) after a 12 month pandemic. Methods: #COVID19PS is a cro ss sectional analytical study using an ad hoc questionnaire distributed through social media to record physical and psychological symptoms related to COVID 19 in health professionals. Variables: age, sex, geographical origin, profession, characteristics of the work environment, physical symptoms, Maslach test ( for health professionals. Univariate and bivariate statistical analysis using t distribution, Chi square, ANOVA using IBM SPSS v20®. Results: N=1.159 ( women, 21.8% men; 44.6% <35 years old, 23.9% between 35 45years); 96.5% Spaniards. Professions: 17.1% medicine, 12.7% nursing, 32% physiotherapy, 24.1% occupational therapy, 14.1% others; 47.5% belonged to direct care for COVID 19 patients. 28.2% had passed the disease and 3.7% had it acti ve. 61.6% had physical symptoms ( neurological, 31.7% musculoskeletal, 29.6% general, 20.9% gastrointestinal, 20.3% skin, 19.2% cardiovascular, 16% respiratory (p= 96.9% had a medium high Burnout index (p= 48.3% with high levels of Emot ional Exhaustion, 62.9% with medium high level of Depersonalization and 74% with medium low levels of Personal Accomplishment. Conclusion: all health professions present high rates of physical and burnout consequences of the first year of COVID 19 pandemic.

Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.

The outbreak of the COVID-19 pandemic has raised concerns about potential environmental factors that could influence the spread and severity of the SARS-CoV-2 virus. Atmospheric pollution, particularly particulate matter (PM), has been suggested as a contributing factor to viral infections and respiratory complications. This two-year observational study aimed to investigate the relation between air pollution and the spread of COVID-19, focusing on PM2.5. Unlike previous studies limited to specific cities or countries, inevitable to use temporal data. Our research analyzed data from various states across the United States, considering both spatial and temporal correlation. The analysis considered the number and geographic distribution of COVID-19 cases along with daily PM2.5 exposure levels, accounting for monthly average PM2.5 exposure, from March 2020 to December 2021. The observed conflicting results of the temporal and spatial correlation present challenges for researchers in understanding the true nature of the relationship between PM2.5 air pollution and COVID-19 cases. The correlation between various factors, such as population density, PM2.5, temperature, and wind speed, and COVID-19 refers to an association or statistical relationship, not causation. Moreover, the intricate interplay of these variables makes it difficult to establish a clear cause-and-effect relationship.

The COVID-19 pandemic caused significant training disruptions during the 2020-21 season due to lockdowns, quarantines, and strict adherence to pandemic protocols. The main purpose of this study was to determine how pandemic training restrictions affected training volume and performance in one collegiate swim team. Cumulative training volume data, across a 28-week season, were compared between a pandemic (2020-2021) versus non-pandemic (2019-2020) season. Swimmers were categorized into three groups (Sprinters, Mid-Distance, and Long-Distance) based on training group. Performance times in 25 swimmers who competed in Regional Championships, during both the non-pandemic and pandemic year, were compared via 1-way ANOVA. 26 male and 22 female swimmers commenced the 2020-21 (pandemic) season, with 23% of swimmers voluntarily opting out. Three COVID-19 cases were confirmed (2%) by the medical staff with no long-term effects. Significant reductions in average swim volume were verified in Sprinters (32,867±10,135 vs.14,800±7,995yards;p<0.001), Mid-Distance (26,457±10,692 vs.17,054±9.923yards;p<0.001), and Long-Distance (37,600±14,430 vs.22,254±14,418yards;p<0.001) swimmers (non-pandemic vs. pandemic season, respectively). In the Regional performance analyses, the Sprinters swam faster (n=8;-0.5±0.6secs), while Mid-Distance (n=10;0.17±2.1secs) and Long-Distance (n=7;6.0±4.9secs) swimmers swam slower (F=11.76;p=0.0003;r²=0.52). Thus, the pandemic caused significant reductions in swim training volume, with Sprinters performing better and Long-Distance swimmers performing worse at Regional Championships.

The COVID-19 pandemic is the biggest public health threat facing the globe today. Multiple vaccines have been approved, however the emergence of viral variants such as the recent Omicron, raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac) vaccine was used, however it’s important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had history of infection by SARS-CoV-2 prior to immunization and others not. We analyzed RBD-specific and neutralizing- antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45-90 days post infection or vaccination, followed by a steady decline over time. In those with previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection followed by immunization resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease.

In the post-pandemic era, evaluating long-term immunity against COVID-19 has become increasingly critical, particularly in light of continuous SARS-CoV-2 mutations. This study aimed to assess long-term immunogenicity by analyzing booster shots’ impact and sera infection history collected in Makassar, Indonesia. We measured anti-RBD IgG levels and neutralization capacity (NC) against both the wild-type (WT) Wuhan-Hu and Omicron XBB 1.5 variants across groups of COVID-19 vaccinated individuals with no booster (NB), single booster (SB), and double booster (DB). The mean durations since the last vaccination were 25.11 months, 19.24 months, and 16.9 months for the NB, SB, and DB group, respectively. Additionally, we evaluated the effect of breakthrough infection (BTI) history, with a mean duration since the last confirmed infection of 21.72 months. Our findings indicate fair long-term WT antibody (Ab) titers, with the DB group showing significantly higher level than other groups. Similarly, the DB group demonstrated higher anti-Omicron XBB 1.Ab titer, which was insignificantly different from the other groups. Although the level of anti-WT Ab was moderate, we observed near-complete (96-97%) long-term neutralization against the WT pseudo-virus for all groups. There was a slight decrease in NC against Omicron XBB 1.5 compared to the WT among all groups; DB group, SB group, and NB group showed 80.71±3.9%, 74.29±6.7%, and 67.2±6.3% neutralization activity, respectively. Breakdown analysis based on infection and vaccine status showed that booster shots increase the NC against XBB 1.5. Individuals with BTI demonstrate a better NC compared to their counterpart uninfected individuals with the same number of booster shots. Our findings suggest that long-term immunity against SARS-CoV-2 persists and is effective against the mutant variant. Booster shots enhance the NC especially among uninfected individuals .

The literature is scarce in the evaluation of Behçet’s disease (BD) among individuals during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Then, an epidemiological study was conducted using the data from 46 hospitalized patients with BD and coronavirus disease (COVID)-19 representing a prevalence of 2,11 patients per 100,000 inhabitants. From the study sample, 58.7% (27 patients) were female, and 67.4% (31 patients) were White. The main symptoms were fever (40; 87.0%), cough (38; 82.6%), dyspnea (35; 76.1%), and peripheral saturation below 95% (35%, 76.1%). The need for intensive care unit support occurred for 39.1% (18) patients. Also, 21.7% (10) patients needed invasive ventilatory support and 47.8% (22) needed non-invasive ventilatory support. A total of 73.9% (34) of patients lived, and 26.1% (12) of patients died. Only the presence of respiratory discomfort [37.9% vs. 5.9%] was more common among those who died. Patients with BD were not at an increased risk of worse COVID-19 outcomes in Brazil.

This study presents the interaction with human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a Protein-Protein-Interaction Networks analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2,753 proven interactions and 1,708 interactors, specific to ORF7b. We used these proteins as functional seeds and we got a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. Seven high ranked proteins as hub and seven as bottleneck following a hub-and-spoke network-architectural-model were found. Through this interaction model, we identified significant GO-processes (5,057 terms in 15 categories) induced in human metabolism by ORF7b. High statistical significance processes of dysregulated molecular cell mechanisms by the action of ORF7b were discovered. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems and the molecular mechanisms that supervise to programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant-Connected-Components core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b mainly acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation, transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes, within the limits of the poor knowledge that these sectors still impose.

Disadvantaged groups around the world have suffered and endured higher mortality during the current COVID-19 pandemic. This contrast disparity suggests that socioeconomic and health-related factors may drive inequality in disease outcome. To identify these factors correlated with COVID-19 outcome, country aggregate data provided by the Lancet COVID-19 Commission subjected to correlation analysis. Socioeconomic and health-related variables were used to predict mortality in the top 5 most affected countries using ridge regression and extreme gradient boosting (XGBoost) models. Our data reveal that predictors related to demographics and social disadvantage correlate with COVID-19 mortality per million and that XGBoost performed better than ridge regression. Taken together, our findings suggest that the health consequence of the current pandemic is not just confined to indiscriminate impact of a viral infection but that these preventable effects are amplified based on pre-existing health and socioeconomic inequalities.

Introduction Most cases of COVID-19 coronavirus infection occurred in the Chinese city of Wuhan at the end of December 2019 in the form of acute pneumonia. COVID-19 virus infects people of all ages. The most affected elderly people with underlying medical conditions. This may cause various symptoms such as fever, difficulty breathing, lung infection, coughing and sneezing. Aim The aim of the present study to highlight the COVID-19 pandemic in Saudi Arabia. Method A search was conducted using the relevant keywords to retrieve the studies conducted in Saudi Arabia regarding COVID-19. The search was by Google Scholar, Pub MED, and Twitter. Conclusion The COVID-19 pandemic carries multiple-risk, and public health groups, such as the United States' Centres for Disease Control and Prevention (CDC) and the World Health Organisation (WHO), are monitoring the pandemic and posting updates on their website. These groups have also made recommendations on disease prevention and treatment, and according to the Saudi Centres for Disease Control, they have also included the necessary public health measures for mandatory reporting by calling a certain number and through the e-health monitoring network.

The aim of the article is to determine the predictors of mental health among Polish society. Research was conducted after the first wave of the pandemic. Due to such an approach, it was possible to determine whether secondary effects of the pandemic have impact on mental health, apart from socio-demographic and psychological factors. In order to gather the research material, the CAWI on-line survey method was applied and carried out within the framework of the Ariadna Research Panel on the sample of 1079 Poles aged 15 and over. The FCV-19S scale, which is used to measure the fear of COVID-19 was applied in the measurement. It is a verified diagnostic instrument used to measure mental health in a lot of countries. The results of a hierarchical regression analysis have shown that the factors which increase the level of fear of COVID-19 are demographic, social and psychological features as well as attitudes towards the pandemic. The results of research indicate the significance of social context in the analysis and explanation of the effects of disasters and cataclysms.

SARS-CoV-2, the causal agent of the globally spreading COVID-19, is capable of infecting variable animals besides human being. We evaluated the potential susceptibility of important livestock, pets and aquatic mammals by performing a multi-species sequence analysis of ACE2 based on the reported affected and unaffected animals. We identified a triple amino acid pattern of ACE2, at position 30, 31 and 34, that might be associated with SARS-CoV-2 infection and H34 might be an indicator of the susceptibility to COVID-19.

While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine for other potential interactions between the virus and other cell receptors. Based on the clinical observation of low smoking prevalence among hospitalized COVID-19 patients, we recently identified a “toxin-like” amino acid (aa) sequence on the receptor binding domain of the spike glycoprotein of SARS-CoV-2 (aa 375-390) with homology to a sequence of a snake venom toxin, which could interact with nicotinic acetylcholine receptors (nAChRs). We now present computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 spike glycoprotein and the extracellular domain of the nAChR alpha9 subunit. We identified an interaction between the aa381-386 of the SARS-CoV-2 spike glycoprotein and the aa189-192 of the extracellular domain of the nAChR alpha9 subunit, a region which forms the core of the “toxin-binding site” of the nAChRs. The mode of interaction is very similar to the interaction between the alpha9 nAChR and alpha-bungarotoxin. A similar interaction was observed between the pentameric alpha7 AChR and the SARS-CoV-2 spike glycoprotein. Our findings support the hypothesis that severe COVID-19 may be associated with disruption of the nicotinic cholinergic system which could be caused by an interaction between SARS-CoV-2 and nAChRs.

Background: In the current era of globalization, the Indonesian government's problem today is the weakening of nationalism and patriotism among the millennial generation. The large number of foreign cultures that have entered Indonesia has caused a sense of nationalism and patriotism. In addition, Indonesia is also facing the problem of spreading the Covid-19 virus. During the pandemic, various policies set by the government received protests from some circles because they felt their freedom was restricted. Therefore, the awareness of millennial generation nationalism is needed, especially during the Covid-19 pandemic like today. This research aims to make millennials aware of nationalism sense, which mainly to prevent the spread of Covid-19. This research is used to answer the questions of what the problems that arise due to the waning of the spirit of nationalism during the pandemic are? and what efforts should be made to maintain the spirit of nationalism? Methods: This research is a qualitative study using the literature review method. The articles used are research published in 2019 to 2021 in Google Scholar, with keywords that match the topic of millennial generation nationalism in the Covid-19 pandemic. Results and Discussion: The results of the study found that the spirit of Indonesian nationalism during the Covid-19 pandemic was decreasing. The decline in the sense of nationalism is due to several government policies that impact the psychology of society and the Indonesian economy. As a result, society, particularly the millennial generation, must play a role in breaking the chain of the Covid-19 virus's propagation by following the government's health standards. Conclusion: The government and society need to work together to understand nationalism in the millennial generation, especially in dealing with problems caused by the Covid-19 pandemic. Based on this, various efforts need to be made to foster the spirit of nationalism and overcome the Covid-19 pandemic. So that later, it can produce a generation that upholds the value of nationalism in everyday life.

The novel coronavirus has had the world on halt for a few months now. Changes in lifestyles have become a part and parcel of our daily lives, especially for students. With new teaching practices undertaken, new reforms are being made from students in kindergarten to college. This paper presents insights on the changing learning habits of Indian students due to the hit of novel coronavirus (COVID-19). A total of 648 students from various institutes took part in the survey by responding to the questionnaires on time spent by them both for online and offline studies and others asked in closed format options. The insights are derived by comparing the performance of students based on their institute types, hours spent on self-study as well as the assistance provided by the colleges. The overall confidence in particular subjects by the end of the semester is being determined as the end result.

This work presents a compilation of data obtained by clinical psychologists during the Covid-19 pandemic in Brazil. Through searches on social media with #Covid19 and #MentalHealth and the exchange of information on networks of professionals, it was possible to compile and group the main psychological symptoms presented during isolation. Information was clustered according to the period it appeared, in order to guide future situations. Moreover, to prepare a group of clinical psychologists to provide online assistance.

Graph theory plays significant role in every field of science as well as technology. Every situation can be articulated in terms of suitable graphs by using various approaches of graph theory. Considering the recent pandemic in the world and the precautions taken for prevention of the COVID 19, it is the most appropriate way to exercise the graph models with theoretical as well as practical aspects to control this epidemic. This paper defines the variable set, variable graphs and their types with respect to variable vertex sets and variable edge sets. Depending upon the nature of the pandemic, there are four types of Virus graphs. Virus graph I and III are not so perilous for all living beings. Although, Virus graphs II and IV are extremely hazardous for the harmony of the world. In view of different aspects for expand of pandemic, growth types of virus graphs are divided in 1-1, 1-P and 1-all growth types. The COVID19 initially was in Virus graph-I type, but presently it is in Virus graph-II types. We present the table involving the number of infected people after n days with respect to different values of P and growth rates with I0 = 100. Moreover, the country wise starting dates of stages of the virus graph-I and II are specified. The concept of cut sets is applicable for prevention of COVID19 and the whole world is using the same analogy.

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.

Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in people in the city of Wuhan at the end of December 2019, and it has since spread to all continents. Global interest has been focused on discovering a treatment and developing a successful coronavirus vaccine as a result of the emergence of this new coronavirus. In this research, we sequenced the whole genome of the SARS-COV-2 virus that were isolated from 40 patients in Duhok, Iraq. 95 different mutations were identified in our isolation when such the whole genome sequence of the SARS-COV-2 isolated from the city of Wuhan, China (Accession number: NC 045512.2) was matched to the virus's sequence using Sequencing technology (Illumina , USA ) and Assembly method (iVar 1.3.1). Sequence analysis revealed that 38 mutations were found at spike glycoprotein (S), 30 of which were found in the ORF1b , 11 mutations were found in ORF1b ,7,3,2,1 mutations were found in ( N,M,ORF6 ,ORF9 /E ) genes which had been linked to structural changes at various places. The conclusion that the cases in Iraq were of different origins of infections and had a close relationship with the isolates from different country and state were further confirmed by phylogenetic analysis and transmission. The whole genome sequence of the SARS-CoV-2 , which were identified from the Iraqi Kurdistan region, and reported as a first study in Kurdistan region.

Physical distancing and wearing a face mask are key interventions to prevent COVID-19. While this remains difficult to practice for millions of firefighters in fire engines responding to emergencies, the delayed forthcoming of evidence on the physical effectiveness of such safety interventions in this setting presents a major problem. In this field experimental study, we provided initial evidence to close this gap. We examined total aerosol burden in the cabin of a fire engine whilst manipulating crew size, natural ventilation, use of FFP2 respirators and use of SCBA full-face masks during 15-minute driving periods. At the same time, we controlled for crew activity and speaking, vehicle speed, cabin air temperature, pressure and humidity. Limiting the crew size, using FFP2 respirators and not donning SCBA full-face masks was associated with a reduction of the arithmetic mean of total aerosol burden of up to 49%. Natural ventilation as tested in this study was associated with both an increase and a decrease of total aerosol burden. This study provided initial evidence on the physical effectiveness of safety interventions in fire engines to reduce potential airborne transmission of SARS-CoV-2 through aerosols. More research about the physical and clinical effectiveness of such safety interventions is needed.

Currently, entire world is crumbled due to COVID-19 caused by novel SARS-CoV-2. Globally, over 5 million people are infected by SARS-CoV-2 with 6% fatality rate. The surface spike (S) protein plays a key role in the pathogenesis of SARS-CoV-2 by mediating viral entry through human angiotensin converting enzyme 2 (hACE2) receptors on the host cell and there is a big global race to find viral neutralizing antibodies and vaccine against S protein of SARS-CoV-2. Since SARS-CoV-2 evolved into 10 different clades in a very short span, a study on sipke protein mutation is essential to have effective vaccine coverage globally. Based on the mutation analysis of S protein from 166 Indian SARS-CoV-2 genome, a total of 40 different SNPs comprising of 14 synonymous and 26 non-synonymous mutations were observed, and notably, Indian S protein diverged into two major clusters, D614 and G614, with 11 different types. Majority of Indian strains fall in A2a and O clusters. Alarmingly, we have observed six SNPs at RBD and notably two of them at RBM (S438F and S494P). S494P SNP, similar to Bat–SARS like-CoV, may indicate a low ACE2 binding affinity. Interestingly 38% of Indian strains harbor a characteristic D614G SNP which was found predominantly in A2a cluster, mostly comprising USA and European strains with high disease severity. The association of disease severity with D614G SNP is well-correlated in states with high death rate except Maharashtra. Notably, more than 50% of D614G mutation were observed in Northern part of India and 14% in Southern part but not in Kerala and Tamil Nadu strains. Highly conserved motif, D614 (608-VAVLYQDVNCT-618) in upstream and also few downstream, of S1/S2 furin cleavage site may indicate specific key role in efficient interaction with host proteases in pathogenesis. Further studies are warranted to clarify the impact of SD614G SNP association to disease severity . Interestingly, C2367T (Y789Y) synonymous SNP is observed in 37% of Indian strains and notably similar SNPs with degeneracy bases were observed which is a key indication for the possibility of misdiagnosis by Real-Time PCR and revised strategies are needed for the precise diagnosis. Circulation of high number of signature SNPs [D614G and C2367T (Y789Y)] in certain states may be an early indication of emergence of community transmission in India. Further large genome sequence data from India will aid in deep understanding on the diversity of circulating SASR-Cov-2 and its impact on disease severity, origin of imported cases to India, community spread, effect on diagnosis and vaccine coverage.

The COVID-19 infections in Pakistan are spreading at an exponential rate and a point may soon be reached where rigorous prevention measures would need to be adopted. Mathematical models can help define the scale of an epidemic and the rate at which an infection can spread in a community. I used ARIMA Model, Diffusion Model, SIRD Model and Prophet Model to forecast the magnitude of the COVID-19 pandemic in Pakistan and compared the numbers with the reported cases on the national database. Results depicts that Pakistan could hit peak number of infectious cases between June 2020 and July, 2020.

Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. This paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 co-crystallized with COVID-19 spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. In parallel, at all stages, authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 co-crystallized with COVID-19 spike protein. Results: Carnosine emerged as the best known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the co-crystallized protein structure, carnosine bind with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 co-crystallized with COVID-19 spike protein and hence could offer potential mitigating effect against current COVID-19 pandemic.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well-defined in resident physicians and fellows (trainees). We aimed to identify sociodemographic, occupational and community factors associated with SARS-CoV-2 infection among trainees during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in New York City (NYC). In this retrospective cohort study, we administered an electronic survey between June 26 and August 31, 2020 to trainees at the Mount Sinai Health System in NYC to assess risk factors for SARS-CoV-2 infection between February 1 and June 30, 2020. We used Bayesian generalized linear mixed effect regression and structural equation models to examine associations. SAR-CoV-2 infection was determined by self-reported IgG antibody and reverse transcriptase-polymerase chain reaction results and confirmed with laboratory results. Among 2354 trainees invited to participate, 328 (14%) completed the survey and reported test results. The cumulative incidence of SARS-CoV-2 infection was 20.1%. Assignment to medical-surgical units (odds ratio [OR], 2.51; 95% CI, 1.18-5.34), and training in emergency medicine, critical care and anesthesiology (OR, 2.93; 95% CI, 1.24-6.92) were independently associated with infection. Deployment to care for unfamiliar patient populations was protective against infection (OR, 0.16; 95% CI, 0.03-0.73). Community factors were not significantly associated with infection after adjustment for occupational factors. Our findings may inform tailored infection prevention strategies for trainees responding to the COVID-19 pandemic.

Smoking is a risk factor for respiratory infections and there is reasonable concern that it may affect COVID-19 susceptibility and severity. Recent studies have focused on the interaction between smoking (and nicotine) and ACE2 expression, suggesting that ACE2 up-regulation could contribute to enhanced viral cell entry. However, case series have shown that there is an unexpectedly low prevalence of smoking among hospitalized COVID-19 cases. Since early April, we were the first to hypothesize that dysfunction of the nicotinic cholinergic system (NCS) may be implicated in the pathophysiology of severe COVID-19. We recently reported that many of the clinical manifestations of severe COVID-19 could be explained by dysregulation of the NCS. In this study, we present an amino acid sequence in the receptor binding domain of the SARS-CoV-2 Spike glycoprotein which is homologous to a sequence of a snake venom toxin. We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein. These findings suggest that SARS-CoV-2 could potentially interact with acetylcholine receptors causing dysregulation of the NCS and the cholinergic anti-inflammatory pathway.

COVID-19 outbreak started in the Chinese city of Wuhan and spread around the globe in months due to its high contagious level. Hence, this disease posed a great challenge to researchers and mathematicians. Numerous mathematical models have been suggested to visualize the spreading speed and trends of this pandemic. In this paper, a comparison of a widely established and accepted method, the Susceptible-Exposed-Infected-Quarantined-Recovered-Death-Insusceptible (SEIQRDP) model with a newly-proposed fractional-order SEIQRDP is studied. Densely populated Countries of Asia (Pakistan, India, and Bangladesh) have been chosen as data sets and both algorithms have been applied to their data. The same comparison technique has also been used on the data of two polar countries, New Zealand and Russia, that validated our findings. Error comparison of both algorithms has been recorded in a tabulated form which shows multi-fold erroneous trends over WHO data of selected countries.

The article revisits previous viruses such as Ebola to extrapolate the socio-economic implications of the COVID-19. Using secondary sources and the Sustainable Livelihoods Framework (SLF) to guide understanding, the article argues that unless measures are put in place to safeguard smallholder activities in Zimbabwe, COVID-19 has the potential to reproduce the same catastrophic implications created by Ebola in West African countries where peasant food systems where shattered and livelihoods strategies maimed. With a perceptible withdrawal of the government from small-scale farming towards large-scale capital intensive operations, smallholders could now be even more vulnerable. The article concludes that social assistance should now be intensified to protect its vulnerable population from the ravages of COVID-19.

COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves’ disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD is rarely observed post COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED ten days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a single stranded RNA virus which has resulted in the Coronavirus Disease 2019 (COVID-19) pandemic and has infected millions of people all over the world. SARS-CoV-2 has been mutating rapidly resulting in the emergence of multiple variants to escape the host immune system mainly by mutations in its receptor binding domain (RBD) of the spike protein. This rapid evolution of the SARS-CoV-2 posed a great challenge regarding the efficacy and effectiveness of the current SARS-CoV-2 vaccines. The RBD and full-length spike of SARS-CoV-2 is the main target of the neutralizing antibodies. Many SARS-CoV-2 variants are considered to have the potential to escape from the host immune system. In this study, the RBD of Alpha, Beta, Gamma, Kappa and Omicron and the full-length spike of BA.1, BA.2, BA.3, BA.4/5, BQ.1.1 and XBB.1.5 Omicron variants were used as coating antigens in Enzyme Linked Immuno-Sorbent Assay (ELISA) to check the neutralization capability of COVID-19 convalescent sera from patients of first wave of infection occurring in Wuhan. Our results show that the currently circulating Omicron BQ.1.1, XBB.1.5 and previous Omicron BA.1, BA.2 and BA.4/5 do not show significant reduction in neutralization, while Omicron BA.3 and previous variants Alpha, Beta, Gamma, Kappa, and Omicron showed a significantly reduced neutralization when compared to the wild-type Wuhan strain. These results indicate patients recovering from natural infection of early original Wuhan strain may have the potential to resist infection of current circulating variants and the vaccines using the prototype antigen may still working for newly emerged variants.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) utilizes Angiotensin Converting Enzyme 2 (ACE2) as its main receptor for cell entry. We have bioengineered a soluble ACE2 protein termed ACE2 618-DDC-ABD that has increased binding to SARS-CoV-2 and prolonged duration of action. Here we investigated the protective effect of this protein when administered intranasally to k18-hACE2 mice infected with the aggressive SARS-CoV-2 delta variant. k18-hACE2 mice were infected with the SARS-CoV-2 delta variant by inoculation of a lethal dose (2x104 PFU) and followed for up to 14 days. ACE2-618-DDC-ABD (10mg/kg) or PBS was administered intranasally six hours prior and 24 and 48 hours post viral inoculation. All animals in the PBS-control group had succumbed to the disease on day 7 post infection (0% survival) whereas, by contrast, there was only one casualty in the group that received ACE2-618-DDC-ABD (90% survival). Mice in the ACE2-618-DDC-ABD group had minimal disease as assessed by a clinical score and stable weight and both brain and lung viral titers were markedly reduced. These findings demonstrate the efficacy of a bioengineered soluble ACE2 decoy with extended duration of action in protecting against the aggressive delta SARS-CoV-2 variant. Together with previous work these findings demonstrate the universal protective potential against current and future emerging SARS-CoV-2 variants.

Introduction: The need for therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remains unmet. Previous work has shown that a combination of three aromatic plants’ essential oil (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticosa Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care. Methods: 69 adult patients were included in a clinical, Proof-of-Concept (PoC) intervention study. Family physicians implemented the observational study in two arms (intervention and control group) during three study periods (IG2020, n=13, IG2021/22, n=25 and CG2021/22, n=31). The SARS-CoV-2 infection was confirmed by real-time PCR. The CAPeo mixture, was administered daily for 14 days, per os in the intervention group, while the control group received usual care. Results: The PoC study, found that the number and frequency of general symptoms, including general fatigue, weakness, fever and myalgia, decreased following CAPeo administration. The average presence (number) of symptoms decreased in IG (4.7 to 1.4) as well as in CG (4.0 to 3.1) by Day 7 compared to Day 1, representing a significant decrease in cumulative presence in IC (-3.3 vs. -0.9, p<0.001; η2=0.20) on Day 7 and on Day 14 (-4.2 vs. -2.9, p=0.027; η2=0.08). Discussion/Conclusion: Our findings suggest that CAPeo, possesses potent antiviral activity, in addition tο the Influenza A and B and the human rhinovirus HRV14 strains against SARS-CoV-2. The early and effective impact in alleviating key symptoms of COVID-19 may suggest this mixture can act as a complementary natural agent for mild COVID-19 patients

Since the outbreak of the COVID-19 (Coronavirus Disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants by using a molecular docking approach to inhibit the Main Protease (M^pro) and Spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine. A rule of five (RO5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was done by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding / ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine and hydroxychloroquine sulfate (anti-malarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir, but were better than chloroquine and hydroxychloroquine sulfate as M^pro inhibitors. These plant compounds have the potential to be developed as specific therapeutic agents against COVID-19. Several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate which so far are recommended in the treatment of COVID-19. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development lead compounds to treat infections caused by SARS-CoV-2.

Background: COVID-19 is a critical pandemic that has affected human communities worldwide, and there is an urgent need to develop effective drugs. Although there are a large number of candidate drug compounds that may be useful for treating COVID-19, the evaluation of these drugs is time-consuming and costly. Thus, screening to identify potentially effective drugs prior to experimental validation is necessary. Method: In this study, we applied the recently proposed method tensor decomposition (TD)-based unsupervised feature extraction (FE) to gene expression profiles of multiple lung cancer cell lines infected with severe acute respiratory syndrome coronavirus 2. We identified drug candidate compounds that significantly altered the expression of the 163 genes selected by TD-based unsupervised FE. Results: Numerous drugs were successfully screened, including many known antiviral drug compounds such as C646, chelerythrine chloride, canertinib, BX-795, sorafenib, sorafenib, QL-X-138, radicicol, A-443654, CGP-60474, alvocidib, mitoxantrone, QL-XII-47, geldanamycin, fluticasone, atorvastatin, quercetin, motexafin gadolinium, trovafloxacin, doxycycline, meloxicam, gentamicin, and dibromochloromethane. The screen also identified ivermectin, which was first identified as an anti-parasite drug and recently the drug was included in clinical trials for SARS-CoV-2. Conclusions: The drugs screened using our strategy may be effective candidates for treating patients with COVID-19.

The aim of this study was to analyze other possible new markers of severity that can be assessed in patients with type 2 diabetes and SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus and infected with the SARS-CoV-2 virus, and 45 healthy persons as control. The serum level of ceruloplasmin at hospital admission was statistically significant directly correlated with the severity of COVID-19 (Coronavirus disease) (p=0.037) and with the serum level of IL-6 (Interleukine 6) (p=0.000). Ceruloplasmin was statistically significant inversely correlated with serum iron level (p=0.000). However, we observed that ACE (Angiotensin converting enzyme) decreased in severe forms of the infection with SARS-CoV-2 virus in patients with type 2 diabetes (p=0.001). Moreover, the decrease in ACE level was correlated with an increase in IL-6 level in these patients (p=0.001). IL-6 increase was statistically significant inversely correlated with serum iron, transferrin and ACE levels. There was a noticed a decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p=0.000). In addition to the known severity factors in the context of infection with the new coronavirus, decreased concentrations of ceruloplasmin, ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters analyzed at the hospital admission could show the evolution towards the severe forms of infection with the SARS-CoV-2 virus.

Nowadays, the presence of pathogen-specific antibodies in the blood is widely controlled by a serodiagnostic technique based on the lateral flow immunoassay (LFIA). However, its common one-stage format with an antigen immobilized in the binding zone of a test strip and a nanodis-persed label conjugated with immunoglobulin-binding proteins is associated with risks of very low analytical signals. It is caused by the presence of non-specific immunoglobulins in very large excess to the target antibodies in the tested samples thus decreasing their binding with the detected labels. In this study, the first stage of the immunochromatographic serodiagnosis was carried out in its traditional format using a conjugate of gold nanoparticles with staphylococcal immunoglobulin-binding protein A and an antigen immobilized on a working membrane. At the second stage, a labeled immunoglobulin-binding protein was added, which enhanced the coloration of the bound immune complexes. The use of two separated steps, binding of specific antibodies, and further coloration of the formed complexes allowed a significant reducing the influence of non-specific immunoglobulins on the assay results. The proposed approach was ap-plied for the serodiagnosis using a recombinant RBD protein of SARS-CoV-2. As a result, an in-crease in the intensity of test zone coloration by more than two orders of magnitude was demonstrated, which enabled to significantly reduce false-negative results. When testing a panel of 16 positive and 8 negative serum samples, the diagnostic sensitivity of the LFIA was 62.5% for the common format and 100% for the enhanced format; the diagnostic specificity of both variants was 100%.

The coronavirus disease 2019 (COVID-19) was officially declared a pandemic on the 11^th March 2020. It is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), impacting the lower respiratory tract. International travel to Australia during the early stages of the pandemic prior to border closure provided avenues for this virus to spread into Australia. There is little understanding of the clonality of SARS-CoV-2 isolates in Australia, and where they originated. This study aimed to investigate the clonality and ancestral sources of SARS-CoV-2 isolates in Australia using in silico methods. We retrieved 1,346 complete genomes from Australia along with 153 genomes from other countries from the NCBI nucleotide database and Global Initiative On Sharing All Influenza Data (GISAID). We then constructed a representative population of 270 sequences for downstream phylogenetic analysis and ancestral area reconstruction. Overall, two major clusters, one stemming from Europe and another from Asia, especially East Asia, were observed, implying at least two major transmission events with subsequent clades confirming the multiclonality of Australian isolates. We also identified three potential dissemination routes of SARS-CoV-2 into Australia. This study supports the hypothesis of multiple clonality and dispersals of SARS-CoV-2 isolates into Australia.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

The Corona Virus (COVID-19) pandemic situation has posed significant effect on tourism industry. Tourism destinations have embraced emergency health care measures and restrictions imposed on human movement around the world. Beaches and resorts are empty, peoples’ movements are stopped and travelling between territories is strictly controlled. The COVID-19 lockdown around the world has imposed negative impact on the livelihood of people and world economy as well. The present study attempts to find out the scopes for sustainable tourism development in near future from the consequences of social, economic, and environment in COVID-19 pandemic situation.

The current Coronavirus Disease 19 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, is unprecedented in recent history and threatens the lives and livelihoods of billions worldwide. The rapid spread and lack of modern parallels have left governments, health agencies, and the public racing to understand how to best mitigate and ultimately suppress the pandemic, but we are still working to understand the strengths and weaknesses of various interventions at our disposal. Few issues have been as contentious as the public use of face masks to control the pandemic’s spread. There is ongoing debate about their effectiveness, but an increasing body of evidence suggests that masks could be a useful in preventing the spread of coronavirus, leading several governments and health agencies to review and revise their policies. Here, we review the theory and evidence behind use of masks. The theory behind masks is that they prevent the spread of viral particles by infected persons, and inhalation of viral particles by uninfected persons. Even assuming masks are not 100% effective in preventing infection, they may reduce severity of infection by reducing viral dosing. Laboratory studies suggest masks may be effective in stopping both exhalation and inhalation of viral particles. However, real-world studies provided limited evidence for the use of masks in controlling influenza transmission and highlight potential problems associated with their misuse, such as poor compliance or improper use. Evidence for efficacy of face masks against the first SARS virus, SARS-CoV-1, implies that they may be effective against the current outbreak of SARS-Cov-2 virus. This is important as mathematical modeling suggests that even small reductions of in transmission rates can make a large difference over time, potentially slowing the pace of viral pandemics and limiting their spread. Perhaps the strongest argument for the use of masks is that countries with early adoption of masks have tended to see flatter pandemic curves, even without strict nationwide lockdowns. There is little evidence that respirators are more effective than surgical masks, but this may be due to misuse or poor compliance. Studies suggest some non-medical masks perform on par with medical masks. Improvised masks are less effective than medical masks, but may provide better protection than nothing at all. While many governments now encourage the use of improvised face coverings, more will need to be known about material, design, and who needs to wear masks, and when, to ensure effectiveness. Proper use of masks will also be important; if masks are used improperly or infrequently they may provide limited protection. It is important that public health policy makers consider the debate and the potential of masks as part of multi-faceted coronavirus control strategies.

This paper presents a two-way factor design incorporating both spatial and temporal variation in the prediction of COVID 19 in Africa. In line with this, the impact of COVID-19on the GDP in Africa is well scrutinized. In contrast to the existing works [1–3], this work also extends the two-factor design into the one-way factor design through incorporating covariates into spatial effects. The data rely on the spatial and temporal obtained from WHO datasets [4, 5]. The one-factor design with more covariates is taken into consideration to identify the major potential predictor variables responsible for the deaths and confirmed cases due to COVID 19 in Africa. The MANCOVA considered population density, temperature, humidity; perception, and wind are all considered as co-variates. Simulations show that the two-way analysis of variance has shown that there is a statistically significant difference between the spatial (Fcal= 8.2704, Pvalue= 3.099∗10−6)and temporal (Fcal= 48.7964, Pvalue= 9.147∗10−16) effects. South Africa and Nigeria are highly influencing due to the pandemic where their GDP also relatively mostly declined. A significant economic change is observed before the pandemic and after the outbreak of the pandemic(tcal= 2.9548, Pvalue= 0.01805). COVID 19 negatively influenced the economy of1 most of the African countries. The population density, temperature, and wind are found to be statistically significantly associated with COVID 19 cases and deaths.

The eruption of the COVID-19 pandemic has affected every sphere of life and may forever change how we have always lived and conducted our businesses, and no one can resist the wind of change that is blowing. Of all the sectors of governance, the educational sector, particularly at the tertiary level, appears to have been most greatly affected and therefore requires a more pragmatic approach to resolution. As of 29th June, Sub-Sahara Africa has reported 382,190 cases of COVID-19. In rejoinder to the virus epidemic, several Sub Sahara African governments implement the resolution to slam learning institutions to enclose the infection. Consequently, advanced schooling institutions obliged to reorganize their loom, becoming more digitally become forward, and changing to online platforms.

Background: We studied the outcomes of SARS-CoV-2 (COVID) hospitalizations and their association with myocardial injury and thrombosis. Methods: Retrospective analysis of the National Inpatient Sample 2020 database. Results: We identified 335,799 hospitalizations with COVID. Of these, 1.6% (5,355) were diagnosed with non-ST-segment myocardial infarction (COVNSTEMI). The mean age of COVID hospitalizations was 71.7, with 60.50% being males. The population prevalence included 53.10% Whites, 17.80% Blacks, 19.20% Hispanics, and 4.10% Asians. The average length of stay (LOS) was 10 days, and 37.60% of patients died during their hospitalization. The average cost of hospitalization (TOTCHG) was $156,633. The COVSTEMI group comprised 1,364 cases, with a mean age of 67.4, in-hospital mortality of 47.4%, and the mean TOTCHG was $177,600. The DVTCOV group comprised 2,869 cases, while the PECOV group had 4,828 cases. Male predominance was observed in both groups, with mean ages of 66 years in the DVTCOV group and 64 years in the PECOV group. The DVTCOV group had a LOS of 16 days, with 24.71% mortality, while the PECOV group had a LOS of 11 days, with 19.20% mortality. The average TOTCHG in the DVTCOV group was $248,900, whereas it was $145,378 in the PECOV group. Conclusion: Our study revealed significant mortality rates across different groups, including 38% in COVNSTEMI, 47% in COVSTEMI, 25% in DVTCOV, and 19% in PECOV. These findings highlight the severity of COVID-related complications and the substantial financial burden of hospitalization.

Due to the health crisis caused by SARS-CoV-2, the creation of a new vaccine platform based on mRNA was implemented. Globally, around 13.32 billion COVID-19 vaccine doses of diverse platforms have been given, and up to this date, 69.7% of the total population received at least one injection of a COVID-19 vaccine. Although these vaccines prevent hospitalization and severe forms of the disease, increasing evidence has shown they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Recent research has also raised concerns that mRNA vaccines could induce immune tolerance, which, added to that caused by the virus itself, could complicate the clinical course of a COVID-19 infection. Furthermore, recent investigations have found high IgG4 levels in people who were administered two or more injections of mRNA vaccines. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. Altogether, evidence suggests that the reported increase in the IgG4 levels detected after repeated vaccination with the mRNA vaccines is not a protective mechanism; rather, it may be a part of the immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. IgG4-induced suppression of the immune system due to repeated vaccination can also cause autoimmune diseases, promotes cancer growth, and autoimmune myocarditis in susceptible individuals.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induce the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted in the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions which share high identity between SARS-Cov-2 anti-gens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

The COVID-19 pandemic has led to a significant and enduring influence on global health, in-cluding maternal and fetal well-being. Evidence suggests that placental dysfunction is a potential consequence of SARS-CoV-2 infection during pregnancy, which may result in adverse outcomes such as preeclampsia and preterm birth. However, the molecular mechanisms underlying this association remain unclear, and it is uncertain whether a mature placenta can protect the fetus from SARS-CoV-2 infection. To address the above hiatus, we conducted a transcriptome-based study of the placenta in both maternal and fetal compartments. We collected placental samples from 16 women, immediately after term delivery, of which seven had confirmed SARS-CoV-2 in-fection by PCR before parturition. Notably, we did not detect any viral load in either the maternal or fetal compartments of the placenta, regardless of symptomatic status. We extracted total RNA from placental tissues, separately from maternal and fetal compartments, constructed cDNA li-braries, and sequenced them to assess mRNA and small RNA expression. Our analysis revealed 727 differentially expressed genes (DEG) in the maternal placental tissue, with 608 upregulated and 109 downregulated in SARS-CoV-2-positive women compared with healthy, negative wom-en. In contrast, the fetal compartment did not exhibit any significant changes in gene expression with SARS-CoV-2 infection. Specifically, we observed significant downregulation of seven genes belonging to the pregnancy-specific glycoprotein (PSG), related to the immunoglobulin superfam-ily in the maternal compartment with active SARS-CoV-2 infection (fold change range from -13.70 to -5.28, FDR ≤ 0.05). Additionally, comparing symptomatic women with healthy, we identified 14,223 DEGs, with high expression of the inflammatory cytokine IL6 in the maternal placenta of the symptomatic women. Furthermore, KEGG analysis revealed that pathways relat-ed to viral infection, vascular smooth muscle contraction, and oxytocin signaling were altered significantly in symptomatic women. Overall, our study sheds light on the molecular mechanisms underlying the reported clinical risk of preeclampsia and preterm delivery in women with SARS-CoV-2 infection. Nonetheless, studies with larger sample sizes are warranted to further deepen our understanding of the molecular mechanisms of the placenta’s anti-viral effects in ma-ternal SARS-CoV-2 infection.

Abstract: This brief policy is written after experience treating COVID-19 positive radiation therapy patients to reduce risk to therapy staff and patients in radiation oncology department. It is important to prioritize the safety of staff and non-infected patients while ensuring the continuation of radiation oncology services. Radiation therapists have sustained contact with covid-19 patients in an enclosed vault. Protocols for correct disinfecting of equipment and room and therapists following methods for less transmission of virus is crucial. This policy covers prevention methods from COVID-19 transmission from patient to patient, patient to staff, staff to patient and staff to staff as follows A.Risk reduction by screening and preparing staff and rooms B.Radiation Therapist Policy for COVID-19 positive patient with CCC (Critical Cancer Care)

Abstract: It is assumed that upon SARS-CoV-2 infection granulocytes can undergo potentially destructive oxidative burst. Therefore, the aim of this study was to evaluate some parameters of redox and inflammatory signaling in granulocytes of recovered and of deceased COVID-19 pa-tients. Granulocytes were isolated from the blood of 32 COVID-19 patients on admission to the hospital (16 survived and 16 died within a week). The levels of proteins (immunoassay), eico-sanoids (UPLC-MS) and antioxidants activity (spectrophotometry) were examined. Enhanced activation of Nrf2 and NFκB and the levels of heme oxygenase and proinflammatory cytokines where found in granulocytes of all COVID-19 patients, while Cu,Zn-SOD and Mn-SOD activities were decreased, especially in deceased patients. Moreover, in patients who died increased levels of pro-inflammatory eicosanoids (PGE2 and TXB2) and decreased of anti-inflammatory (15d-PGJ2 and 5-HETE) were observed. However TXB2 was decreased, and IL-2 and IL-10 levels were in-creased in survivors, if compared both to healthy subjects and deceased patients, who did not change their cytokine generation. Therefore, it seems that by triggering transcription factors granulocytes activate redox signaling, leading to the production of pro-inflammatory eicosanoids, while reducing cellular antioxidant capacity via SOD, they express altered response to COVID-19, which might result in the onset of the vicious cycle of systemic oxidative stress in deceased patients.

The COVID-19 pandemic has forced Indian engineering institutions (EIs) to bring their previous half-shut shades completely down. Fetching new admissions to EI campuses during the pandemic has become a ‘now or never’ situation for EIs. During crisis situations, institutions have struggled to return to the normal track. The pandemic has drastically changed students’ behavior and family preferences due to mental stress and the emotional life attached to it. Consequently, it becomes a prerequisite, and emergencies need to examine the choice characteristics influencing the selection of EI during the COVID-19 pandemic. The purpose of this study is to critically examine institutional influence and pandemic influence due to COVID-19 that affects students’ choice about an engineering institution (EI) and consequently to explore relationships between institutional and pandemic influence. The findings of this quantitative research, conducted through a self-reported survey, have revealed that institutional and pandemic influence have governed EI choice under the COVID-19 pandemic. Second, pandemic influence is positively affected by institutional influence. The study demonstrated that EIs will have to reposition themselves to normalize pandemic influence by tuning institutional characteristics that regulate situational influence and new enrollments. It can be yardstick for policy makers to attract new enrollments under pandemic situations.

Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.

Unprecedented in scale, immense COVID-19 immunization programmes have been rolled out globally. This article explores aspects of hypothetical vaccine acceptability in Soweto, South Africa, shortly before such vaccines became available. Whereas hypothetical acceptance was normative, this has not translated into uptake today, which remains concerningly low in South Africa, especially in Soweto. For that reason, we mobilise anthropological concepts to analyse acceptance, hesitancy, and denial, respectively, to gauge and understand public proclivity to inoculate. We find that COVID-19’s haphazard mediatization generated a ‘field of suspicion’ towards authorities and vaccination, which, amplified by dis- and misinformation, fostered othering, hesitancy, and denial considerably. It remains paramount during vaccination rollouts to unveil and address aspects detrimental to vaccine confidence and selectivity, especially in lower-income groups for underlying, context-specific cultural, spiritual, historical, and socioeconomic reasons. Appropriate mediazation alongside a debunking of counterfactual claims is crucial in driving forward immunization.

A population-based seroepidemiological and molecular survey for detection of earlier and re-cent SARS-CoV-2 infection was done in children aged 14 years or less in Tehran between 19 September 2020 and 21 June 2021. Demographic data, COVID-19 symptoms and infection status were recorded and IgG antibodies and RNA of SARS-CoV-2 were detected in sera and nasopha-ryngeal swab samples, respectively. Out of 1517 participants, cardinal symptoms of COVID-19 (fever >38 oC and/or cough and/or diarrhea) were detected in 18% and serological history of SARS-CoV-2 infection and PCR positivity were confirmed in 33.2% and 10.7% of the weighted-population, respectively. SARS-CoV-2 infection was significantly higher among 10–14-year-old children. Active infection was significantly higher in symptomatic children and during autumn 2020 and spring 2021. The RT-qPCR positivity was related to contact with in-fected persons. RT-qPCR positivity was significantly higher among families with a lower socio-economic status, while no association between RT-qPCR- or seropositivity was determined with household size, underlying diseases, or gender. In conclusion, high SARS-CoV-2 infection prev-alence and seroprevalence was detected in children in Tehran in different seasons. The infection was significantly higher in older age children, and those with a positive-history of close contact with infected cases and/or lower socioeconomic status.

Background and Objectives: The COVID-19 pandemic influenced the management of patients with immune mediated rheumatic and musculoskeletal diseases (imRMDs) in various ways. The goal of our systematic review was to determine the influence of the first period of the COVID-19 pandemic on the management of imRMDs. Materials and Methods: Systematic literature search of PubMed, Cochrane and Embase databases, including studies with adult patients on the influence of the COVID-19 pandemic on management of imRMDs. There were no restrictions regarding to study-design except for systematic reviews and case reports that were excluded as well as articles on the disease outcomes in case of SARS-CoV-2 infection. Two reviewers screened the studies for inclusion, and, in case of disagreement, consensus was reached after discussion. Results: A total of 5969 potentially relevant studies were found, and, after title, abstract and full-text screening, 35 studies were included with data from 182’746 patients and 2018 rheumatologists. Non-availability of drugs, e.g., hydroxychloroquine and tocilizuab, was frequent (16–69% of patients). Further, medication non-adherence was reported among patients with different RMDs and between different drugs in 4–46% of patients. Changes to preexisting medication were reported in up to 33% of patients (e.g. reducing dose of steroids or cessation of biological disease-modifying antirheumatic drugs). Physical in-office consultations and laboratory testing decreased and as a consequence newly implemented remote consultations increased greatly with an increase of up to 80%. Conclusion: The COVID-19 pandemic influenced the management of imRMDs, especially at the beginning. Influences were wide-ranging, affecting availability of pharmacies, adherence to medication or medication changes, doctor visits and laboratory testing. New systems of care were set up, including virtual clinics and video consultations. These new forms of health care delivery should be spread and implemented worldwide to routine clinical practice to be ready for future pandemics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.

COVID-19 has been extremely difficult to control. The lack of understanding of key aspects of pandemics has affected virus transmission. On the other hand, there is a demand to incorporate Computational Thinking (CT) in the curricula with applications in STEM. However, there are still no exemplars in the curriculum that apply CT to real-world problems such as controlling a pandemic or other similar global crises. In this paper, we fill this gap by proposing exemplars of CT for modeling the pandemic. We designed exemplars following the three pillars of the APEC InMside framework for CT: algorithmic thinking, computational modeling, and machine learning. For each pillar, we designed a progressive sequence of activities that covers from elementary to high school. In an experimental study with elementary and middle school students from 2 schools of high vulnerability, we found that the computational modeling exemplar can be implemented by teachers and correctly understood by students. We conclude that it is feasible to introduce the exemplars at all grade levels, and that this is a powerful example of STEM integration that helps reflect and tackle real-world and challenging public health problems of great impact for students and their families.