The probability of zoonoses, such as the novel coronavirus (COVID-19), emerging is strongly related to remediable factors such as habitat encroachment and trade in wild animals. Tackling these underlying determinants is important to prevent future pandemics from the approximately 700,000 viruses with the potential to cause zoonoses. Reversing habitat destruction is also vital to halt the accelerating rate of extinction of a wide array of life forms - with all the adverse consequences these extinctions will have for human health. These insights depend on viewing health and disease from within an ecological theoretical framework. We therefore argue that preventing future zoonotic outbreaks as well as dealing with a range of contemporary health issues would be facilitated by grounding our health sciences in more a more explicitly ecological conceptual framework.

Evidence for the potential for airborne transmission of SARS-CoV-19 continues to accumulate, with important implications for healthcare workers, as well as the general public. Three lines of evidence support this conclusion.

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.

The Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) first emerged in 2019 in China and has resulted in millions of human morbidities and mortalities across the globe. It has been shown that this novel virus originated in animals, mutated, and made the cross-species jump to humans. At the time of this communication, the Coronavirus disease (COVID-19) may be on way to an endemic form, however the threat of the virus is more for susceptible (older people and immunocompromised) people. The human body has more bacterial cells than its own, thus making us more bacterial than humans. As a consequence, the bacteriomes in the human body heavily influence human health and disease. The bacteriomes in the body and the immune system seem to be in constant association during bacterial and viral infections. In this review, we identify various bacterial spp. in major bacteriomes (oral, nasal, lung, and gut) of the body in healthy humans and compare them with dysbiotic bacteriomes of COVID-19 patients. We try to identify key bacterial spp. that have a positive effect on the functionality of the immune system and human health. These select bacterial spp. could be used as potential probiotics to counter or prevent COVID-19 infections. In addition, we try to identify key metabolites produced by probiotic bacterial spp. that could have potential anti-viral effects against SARS-CoV-2. These metabolites could be subject to future therapeutic trials to determine their anti-viral efficacy.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents was not yet available. Given Omicron’s high transmissibility, the ability to assess its impact on admission and hospitalization rates in children’s hospitals is critical for the purpose of understanding the scope of its burden on the German health care system. (2) Methods: From January 24, 2022 to July 31, 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and need for respiratory support were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4–3) per reporting pediatric hospital per day were hospitalized on general wards, whereas a median of 0.1 cases (range 0–0.4 cases) were on intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with need for intensive care treatment and respiratory support due to a symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children’s hospitals.

Background: In the span of just two years, tracking the COVID-19 pandemic through wastewater surveillance has advanced from early reports of successful SARS-CoV-2 RNA detection in untreated wastewater to implementation of programs in at least 60 countries. Early wastewater monitoring efforts primarily originated in research laboratories and are now transitioning into more formal surveillance programs run in commercial and public health laboratories. A major challenge in this progression has been to simultaneously optimize methods and build scientific consensus while implementing surveillance programs, particularly during the rapidly changing landscape of the pandemic. Translating wastewater surveillance results for effective use by public health agencies also remains a key objective for the field. Objectives: We examine the evolution of wastewater surveillance to identify model collaborations and effective partnerships that have created rapid and sustained success. We propose needed areas of research and key roles academic researchers can play in the framework of wastewater surveillance to aid in the transition of early monitoring efforts to more formalized programs within the public health system. Discussion: Wastewater surveillance has rapidly developed as a public health tool Clinical testing programs are ramping down and home testing is on the rise, making wastewater monitoring important for future surveillance of COVID-19. Our experience in initiating and implementing wastewater surveillance programs in the United States has allowed us to reflect on key barriers and organizational challenges and draw useful lessons. As wastewater surveillance programs are formalized, the working relationships developed between academic researchers, commercial and public health laboratories, and data users should continue and should promote knowledge co-development. While wastewater surveillance has demonstrated utility for tracking COVID-19, there remain technical challenges and open scientific questions that researchers are equipped to address, which will contribute to building robust surveillance programs that provide public health practitioners with new insights into population health.

A novel coronavirus strain (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first appeared in December 2019 and can cause acute respiratory distress syndrome and death. However, there are only limited therapy choices and no vaccine for SARS-CoV-2 is currently available. Here we report about a case of a SARS-CoV-2 caused pneumonia successfully treated with thalidomide. Thalidomide is an immunomodulatory and anti-inflammatory agent and was combined with a low-dose glucocorticoid. We suggest, that the effects of thalidomide might be related to regulating immunity, inhibiting the inflammatory cytokine surge, alleviating anxiety to reduce oxygen consumption, relieving vomit and lung exudation.

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL^-1 s^-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host and the possible outcomes of host-pathogen interaction.

Background: The aim of this study was to investigate the persistence of SARS-CoV-2 in post-mortem swabs of subjects who died from SARS-CoV-2 infection. Methods: The presence of the virus was evaluated post-mortem from airways of 27 SARS-CoV-2 positive patients at three different time points (T1 2 hours; T2 12 hours – T3 24 hours) by real-time PCR. Detection of antibodies to SARS-CoV-2 was performed by Maglumi 2019-nCoV IgM/IgG chemiluminescence assay. Results: SARS-CoV-2 viral RNA was still detectable in 70,3% of cases within 2 hours after death and in 66,6% of cases up to 24 hours after death. Our data showed an increase of the viral load in 78,6% of positive individuals 24 hours post-mortem (T3) in comparison to that evaluated 2 hours after death (T1). Noteworthy, we detected a positive T3 post-mortem swab (24 hours after death) from 4 subjects who were negative at T1 (2 hours after death). Conclusion: The results of our study may have an important value in the management of deceased subjects not only with a suspected or confirmed diagnosis of SARS-CoV-2, but also for unspecified causes and in the absence of clinical documentation or medical assistance.

It is highly likely that the wearing of face masks reduces the rate of respiratory infections (e.g. SARS-CoV-2), to protect both the user and those around them. This paper sets out to review the areas that effect the efficacy of masks, the materials, design, hygiene and fit testing, in order to make recommendations as to how to make mask from resources found in most homes for when commercial models are unavailable. This paper finds that a mask constructed with a filter made from high thread count cotton is likely to provide a reasonable level of protection (~70% filtration) and that if a layers of other materials such as chiffon or silk is added the filtration may be much higher (~90%). There is also some promise in less available materials such as vacuum cleaner bags and air conditioner filters. Examples of fabric and rigid designs are reviewed but most are limited by the fit to the users which is hard to determine in a home setting. It would be extremely helpful if a method was devised for people to test or be tested for the fit of home made masks. In the mean time careful thought should be given to whether the user judges a good fit. Users should also be careful to practice other means of hygiene and distancing.

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in damage to the lungs and other organs. This remarkable increase in cytokines and other inflammatory molecules is primary caused by viral proteins, in particular ORF8, a unique accessory protein specific to SARS-CoV-2. In addition to its role in cytokine induction, ORF8 is attributed with various other functions, including its ability to evade type I interferon responses. Despite the evidence, the mechanisms through which ORF8 exerts these functions remains a subject of controversy. In this mini review, we discuss the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6. We also discuss data from our studies indicating that ORF8 augments production of IL-6 induced by Poly(I:C) in human embryonic kidney (HEK)-293 and monocyte-derived dendritic cells (mono-DCs).

Objective: To identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru. Methods: nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which have been considered mild, moderate and severe cases of COVID-19. Patients had to have tested positive for COVID-19, using a positive RT-PCR for SARS-CoV-2. Subsequently, the SARS-CoV-2 complete viral genome sequencing was carried out using Illumina MiSeq®. The sequences obtained from the sequence were analysed in Nextclade V1.10.0 to assign the corresponding clades, identify mutations in the SARS-CoV-2 genes and perform quality control of the sequences obtained. All sequences were aligned using MAFFT v7.471. The SARS-CoV-2 isolate Wuhan NC 045512.2 was used as a reference sequence to analyse mutations at the amino acid level. The construction of the phylogenetic tree model was achieved with IQ-TREE v1.6.12. Results: it was determined that during the period December 2020 and January 2021, the lineages s C.14, C.33, B.1.1.485, B.1.1, B.1.1.1, B.1.111 circulated, lineage C.14 the most predominant with 76.7% (n=23/30), these lineages were classified in clade 20D mainly and also within clade 20B and 20A. On the contrary, the variants found in the second batch of samples of the period September – October 2021 were Delta Variant (72.7%), Gamma (13.6%), Mu (4.6%), Lambda (9.1%), distributed between clades 20J, 21G, 21H, 21J and 21I. Conclusions: This study reveals updated information on the viral genomics of SARS-CoV-2 in the Lambayeque region, Peru, which is crucial to understanding the origins and dispersion of the virus and provides information on viral pathogenicity, transmission and epidemiology.

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases il-lustrate a common pathway whereby a viral trigger causes clonal expansion of a hematological disorder. Although the association in both cases are temporal, and that COVID-19 may be an in-cidental diagnosis, the growing evidence related to hematological effects of SARS-CoV-2 infec-tion highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era.

SARS-CoV-2 is a novel coronavirus that is the causative agent of Coronavirus infectious disease 2019 (COVD-19). As of the 17^th April 2020, it has infected 2 114 269 people resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.

Following the rapid spread of COVID-19 across the globe, the intense response that was demanded of diagnostic centers and research laboratories prompted the use of numerous products and protocols for the management of SARS-CoV-2 specimens. In these settings, proper handling of such infectious specimen is necessary to ensure the safety of personnel and to reduce the risk of active transmission. Our aim was to evaluate the inactivation efficacy of different inactivating methods, notably from commercial lysis buffers available in diagnostic kits. Heat and sodium dodecyl sulfate detergent were also included in our investigations. A cell culture-based assay was used, and supported by molecular qRT-PCR detection, to show in vitro infectivity reduction after inactivation treatment. Overall, all the investigated methods were successful in inactivating SARS-CoV-2. Ten minutes of contact with the commercial buffers completely stopped in vitro SARS-CoV-2 infectivity. Fifteen minutes at 68°C and 30 minutes at 56°C as well as one hour with sodium dodecyl sulfate detergent at 2, 1, 0.5, and 0.1% yielded the same results. These findings demonstrate the reliability of these protocols with regards to biosafety. Inactivation by heat and sodium dodecyl sulfate detergent are rather simple and can be readily available methods for rendering an infectious SARS-CoV-2 specimen inactive, especially in settings where commercial buffers are not available.

Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A dramatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this second part of the review about Cov2 in aged people, we searched for studies describing the possible efficacy of vitamins A, D, E and C in improving the immune system function and their possible activities against viruses. Results: Vitamins may shift the proinflammatory Th17 mediated immune-response arising in the autoimmune diseases towards a T-cell regulatory phenotype. These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. Conclusion: This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS-CoV-2 infection.

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become a dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its effectiveness against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of September 12, 2023, 429 participants aged ≥18 years were randomized to SCTV01E (N=215) or SCTV01E-2 (N=214) groups. Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group compared to SCTV01E. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase of nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine related SAEs, AESIs or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without safety concerns, underlining its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

3CL^pro is the main protease of the novel coronavirus (SARS-CoV-2) responsible for their intracellular duplication. Based on virtual screening technology, we found 23 approved clinical drugs such as Carfilzomib, Saquinavir, Thymopentin and etc., which showed high affinity with the 3CL^pro active sites. These findings suggest that 3CL^pro inhibitors might be potential candidates for further activity detection and molecular modification.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

Background: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild course; however, about 1% of affected children require a stay in the pediatric intensive care unit (PICU) due to the severe life-threatening course. The risk of respiratory failure, as in adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyze patients admitted to PICUs due to severe course of SARS-CoV-19 infection. Methods: A retrospective multi-center study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection, who were admitted to PICUs, in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, and the endpoint – survival or death. Results: The study analyzed 45 patients (0.075% of all children hospitalized in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n=18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system, Lung Injury Score and Pediatric Sequential Organ Failure Assessment . A significant correlation between disease severity and the patient's prognosis was shown by the liver function parameter AST (p=0.028). Analyzing patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalization, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. Conclusions: As in adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis.

Mitochondria are classically termed as powerhouse of a mammalian cell. Most of the cellular chemical energy in the form of adenosine tri phosphate (ATP) is generated by mitochondria and dysregulation of mitochondrial functions thus can be potentially fatal of cellular homeostasis and health. Acute respiratory distress has been earlier linked to mitochondrial dysfunction. SARS-CoV-2 infection severity leads to acute respiratory distress syndrome (ARDS) and can be fatal. We tried to investigate possible connection between SARS-CoV-2, ARDS and mitochondria. Here, we report identification of SARS-CoV-2 non-structural proteins (particularly Nsp12 and 13) that have recognition sequence with respect to mitochondrial entry. We also report that these proteins can potentially shuttle between cytoplasm and mitochondria based on the localization signals and help in downstream maintenance of the virus. Their properties to use ATP for enzymatic activities may cause ATP scavenging allowing viral RNA functions in lieu of host cell health.

Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms, while others that infect animals can evolve and become infectious to humans. Three recent examples of this viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19).COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 14 April 2020 show more than 2 million people had been infected with the virus, causing more than 120,000 deaths in over 210 countries worldwide. The large amount of information we receive every day concerning this new disease is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry. Because there is limited evidence of active oral infection by SARS-CoV-2 viruses, we assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Viral dynamics in hTERT TIGKs were different from those in A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells at day 3 after infection. Analysis of oral epithelial cells infected by replication competent SARS-CoV-2 viruses expressing GFP showed that the signals of GFP and SARS-CoV-2 mRNAs were not evenly distributed. Taken together, our results demonstrated oral epithelial cells were susceptible to SARS-CoV-2 viruses despite of low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for development of future vaccines and therapeutics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with ACE2 receptor located in endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease leading to irreversible tissue damage and death of patients with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated to the interaction of SARS CoV-2 with ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.

Many reports showed a dramatic decrease in the levels of physical activity during the current pandemic of SARS-COV-2. This has substantial immunometabolic implications, especially in those at risk or with metabolic diseases including individuals with obesity and Type 2 diabetes. Here we discuss the route from physical inactivity to immnometabolic aberrancies; focusing on how insulin resistance could represent an adaptive mechanism to the low physical activity levels and/or high energy intake and on how such an adaptive mechanism could derail to be a pathognomonic feature of metabolic diseases creating a vicious circle of immune and metabolic aberrancies. We provide a theoretical framework to the severe immunopathology of COVID-19 in patients with metabolic diseases. We finally discuss the idea of exercise as a potential adjuvant against COVID-19 and emphasize how even interrupting prolonged periods of sitting with short time breaks of very light activity could be a feasible strategy to limit the deleterious effects of sedentary behavior.

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic affecting approximately 490,000 people and accounting for more than 22,000 deaths and has no generally acceptable cure. Here, the recently resolved 3D structure of SARS-CoV-2 receptor binding domain (RBD) in complex with its receptor-the angiotensin converting enzyme-2 (ACE-2) have provided the basis for screening chemical database for novel entry inhibitors. Methods: Molecular docking protocols have been used to rapidly screen FDA database for high affinity interaction at the SARS-CoV-2-RBD/ACE-2 interface. One of the top candidates, ubrogepant has been selected and further studied using atomistic molecular dynamics simulation method. Results: Molecular docking result showed that ubrogepant (UBR) and darunavir have binding energies of -10.4 kcal/mol. MMPBSA free energy analyses of UBR bound to RBD, ACE-2 and RBD/ACE-2 revealed RBD/ACE-2 > ACE-2 > RBD preference. Network analysis showed that interaction captured in the crystal structure were disrupted in UBR-bound state, hydration of the interface and increased atomic fluctuation within the RBD oligomerization interface and ACE-2 zinc binding site. Conclusions: The ability of ubrogepant to rupture the interaction at the RBD/ACE-2 interface residues of SARS-CoV-2 RBD/ACE-2 complex may result in loss of protein function with direct implication on oligomerization formation in RBD and loss of function in ACE-2 thus, making binding, cellular receptor recognition impossible. General Significance: Ubrogepant represents a new therapeutic candidate in the fight against COVID-19, as it binds with relatively high affinity with free RBD, ACE-2 receptor and SARS-CoV-2 RBD/ACE-2 complex based on binding affinity calculations.

Since December 2019, the worldwide spread of COVID-19 has brought the majority of the world to a standstill, affecting daily lives as well as economy. Under these conditions, it is imperative to develop a cure as soon as possible. On account of some of the adverse side effects of the existing conventional drugs, researchers all around the world are screening natural antiviral phytochemicals as potential therapeutic agents against COVID-19. This paper aims to review interactions of some specific phytochemicals with the receptor binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2 and suggest their possible therapeutic applications. Literature search was done based on the wide array of in-silico studies conducted using broad spectrum phytochemicals against SARS-CoV-2 and other viruses. We shortlisted 26 such phytochemicals specifically targeting the S protein and its interactions with host receptors. To validate the previously published results, we also conducted molecular docking using the AutoDockVina application and identified 6 high potential phytochemicals for therapeutic use based on their binding energies. Besides this, availability of these compounds, their mode of action, toxicity data and cost-effectiveness were also taken into consideration. Our review specifically identifies 6 phytochemicals that can be used as potential treatments for COVID-19 based on their availability, toxicology results and low costs of production. However, all these compounds need to be further validated by wet lab experiments and should be approved for clinical use only after appropriate trials.

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

Several methods can be used to evaluate antibody avidity, one of which is the modified ELISA, in which a chaotropic agent is added to disrupt the binding between the antigen and the antibody. Although the avidity index provides relevant information about the functionality of antibodies, it does not allow us to characterize which antigens the antibodies are strongly bound to. To this end, we adapted the Immunoblot and Dot-Blot techniques by adding potassium thiocyanate (KSCN) after incubating nitrocellulose membranes with serum from mice immunized with Neisseria meningitidis outer membrane vesicles (OMVs) or serum from mice immunized with recombinant receptor-binding domain (RBD) of SARS-CoV-2, with different adjuvants for each antigen. In terms of results, when standardizing the incubation time of sera with KSCN, we observed that 5 minutes was the ideal time for both assays, however, when using different dilutions of serum from mice immunized with RBD, there was an influence on the strength of antigen-antibody binding. For the N. meningitidis assay, the antibodies maintained high avidity for the antigens present in the OMVs, PorA, NadA, and Opa, especially in the presence of the aluminum hydroxide adjuvant. The research showed that standardizing the Immunoblot and Dot-Blot in the same assay optimizes time and resources, allowing qualitative analysis for two different antigens, and resulting in more robust information for immunization studies against these pathogens.

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

Little is understood about the impact of nebulisation on the viability of SARS-CoV-2. In this study, a range of nebulisers with differing methods of aerosol generation were evaluated to determine SARS-CoV-2 viability following aerosolisation. The aerosol particle size distribution was assessed using an aerosol particle sizer (APS) and SARS-CoV-2 viability was determined after collection into liquid media using All-Glass Impingers (AGI). Viable particles of SARS-CoV-2 were further characterised using the Collison 6-jet nebuliser in conjunction with novel sample techniques in an Andersen size-fractioning sampler to predict lung deposition profiles. Results demonstrate that all the tested nebulisers can generate stable, polydisperse aerosols (Geometric standard deviation (GSD) circa 1.8) in the respirable range (1.2 to 2.2µm). Viable fractions (PFU/particle, the virus viability as a function of total particles produced) were circa 5x10^-3 and were not significantly affected by relative humidity. The novel Andersen sample collection methods successfully captured viable virus particles across all sizes; with most particle sizes below 3.3µm. MMADs (Mass Median Aerodynamic Diameters) were calculated from linear regression of log10-log10 transformed cumulative PFU data, and calculated MMADs accorded well with APS measurements and did not differ across collection method types. This data will be vital in informing animal aerosol challenge models, and infection prevention and control policies.

Objective: The objective of the present study was to evaluate the activities of daily living using the Barthel Index, before and after the infection by SARS-COV-2 and to see if the results vary according to sex. Methods: The activities of daily living of 68 cohabiting geriatric patients, 34 men and 34 women, in 2 nursing homes were measured before and after SARS-COV-2 infection using the Barthel index. Results: The Covid 19 infection affects the performance of daily life activities in institutionalized elderly in nursing homes, and it does so especially the older the subject, regardless of sex. Conclusions: The Covid 19 pandemic, in addition to having claimed some victims, especially in the elderly population, has reduced the ability of these people to carry out their activities of daily life, considerably worsening their quality of life despite have been able to overcome the disease.

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

Despite widespread vaccination, early treatments, and improved understanding of the disease, the effects of SARS-CoV-2 infection remain significant worldwide. Many patients still suffer from severe COVID-19, necessitating admission to intensive care units. Remdesivir is a primary treatment option among viral RNA polymerase inhibitors for hospitalized SARS-CoV-2 patients. However, there is a lack of studies examining factors influencing its effectiveness in this context. We conducted a retrospective study throughout 2022, analyzing clinical, laboratory, and sociodemographic data from 252 hospitalized COVID-19 patients treated with remdesivir. Six machine learning algorithms were compared and validated to predict factors associated with the loss of clinical benefit from remdesivir in terms of mortality and hospital stay. Data were extracted from electronic health records. The eXtreme Gradient Boost (XGB) method achieved the highest balanced accuracy for both mortality (95.45%) and hospital stay (94.24%). Factors associated with worse outcomes of remdesivir use in terms of mortality included limitation of life support treatment, need for ventilatory support (especially invasive mechanical ventilation) on day 14 after the first dose of remdesivir, lymphopenia, low levels of albumin and hemoglobin, presence of flu and/or coinfection, and cough. Factors associated with worse outcomes of remdesivir use in terms of hospital stay included the number of doses of the COVID-19 vaccine, patchy lung density, bilateral pulmonary radiological status, number of comorbidities, oxygen therapy, troponin and lactate dehydrogenase levels, and asthenia. These findings highlight the effectiveness of XGB as a strong candidate for accurately categorizing COVID-19 patients undergoing remdesivir treatment.

Background: from December 2019 and the spreading of syndemics, a lot of medical centers reg-istered data about their patients. In Italy, the most relevant quantity of patients was hospitalized in internal medicine wards. Methods: In this observational, retrospective cross-sectional study, all data of the COVID-19 patients, admitted Latio hospitals, from March 01 to December 31, 2020, were collected and their Epidemiological data, demographics, signs and symptoms on admission, comorbidities, laboratory findings, chest radiography and CT findings, treatment received and mortality rate were analyzed by gender to find any differences of gravity of disease. Clinician details were registered on database (one for every hospital). Cost analysis was performed by length of stay and antiviral drugs use, using point of view of Italian Healthcare System. Results: 2256 patients with mean age of 71.01 ± 28.02 years were included. For men, frequency of hyper-tension, COPD, use of oxygen therapy, Tocilizumab were significantly higher and epidemiolog-ical link was related to rehabilitation ward and community. The gender difference about hospi-talization was one day more for man. No strong significant difference by gender in the death rate was observed. Considering antiviral drugs and hospitalization, a man costs €1000 more than woman. Conclusions: In male patients, hypertension and COPD were observed more frequently and the epidemiological link was related to rehabilitation ward and community. In female sub-jects, the epidemiological link was related to Hospital and we observed significantly higher atypical chest-X ray. Tocilizumab, oxygen therapy and antiviral drugs were prescribed more in male subjects. No differences by gender we report in other treatments and outcomes. Future studies should be analyzed to get a more comprehensive understanding of COVID-19 by gender.

Background: This study investigated the biological effects on circulating monocytes after challenge with SARS-CoV-2 recombinant spike protein. Methods: Whole blood collected form seven ostensibly healthy healthcare workers was incubated for 15 min with 2 and 20 ng/mL recombinant spike protein of Ancestral, Alpha, Delta and Omicron variants. Samples were analyzed with Sysmex XN and DI-60 analyzers. Results: Cellular complexity (i.e., presence of granules, vacuoles and other cytoplasmic inclusions) increased in all samples challenged with the recombinant spike protein of Ancestral, Alpha and Delta variants, but not in those containing Omicron. The cellular content of nucleic acids was constantly decreased in most samples, achieving statistical significance in those containing 20 ng/mL of Alpha and Delta recombinant spike proteins. The heterogeneity of monocyte volumes significantly increased in all samples, achieving statistical significance in those containing 20 ng/mL of recombinant spike protein of Ancestral, Alpha and Delta variants. The monocyte morphological abnormalities after spike protein challenge included dysmorphia, granulation, intense vacuolization, platelet phagocytosis, development of aberrant nuclei and cytoplasmic extrusions. Conclusions: The SARS-CoV-2 spike protein triggers important monocyte morphological abnormalities, more evident in cells challenged with spike protein of the more clinically severe Alpha and Delta variants.

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

COVID-19 (coronavirus disease 2019) is a public health emergency of international concern caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of this time, there is no known effective pharmaceutical, phytopharmaceutical or traditional medicine for cure or prevention of COVID-19, although it is urgently needed. In this review, based on the current understanding of the disease molecular mechanisms of novel Coronavirus SARS-CoV-2 and its closest relative SARS-CoV and other human Coronaviruses, I have identified some naturally occurring plant based substances and Ayurvedic medicinal herbs that could feasibly be tested as a matter of urgency for prevention as well as therapeutic option for COVID-19 in India and other parts of the world. I conclude that dried rhizome of Curcuma longa L. i.e. turmeric, and its active ingredient curcumin may be effective in preventing as well as cure the COVID-19 pandemic due to its proven antiviral activities, this however need to be tested by appropriate clinical trials as research priority.

(1) Background: Immunosuppressed patients, especially those receiving B-cells depleting therapies (BCDT), are at major risk to develop reduced vaccine seroconversion and contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. The aim of our study is to assess safety and efficacy of the pre-exposure prophylactic combination of Tixagevimab and Cilgavimab (TGM-CGM) in a cohort of rheumatic patients diagnosed with Autoimmune Rheumatic Diseases; (2) Methods: We performed a prospective study using the clinical medical charts of 25 patients treated with Rituximab and received a single injection of TGM/CGM. The cohort was followed for 6 months from the injection and compared to a control group of 25 immunosuppressed patients who did not receive TGM-CGM. We assessed the incidence and the severity of Covid-19 in both groups, as well as early and late adverse events; (3) Results: Despite the small sample, we noticed a downward trend in the incidence and severity of symptomatic infection in the group treated with TGM/CGM. In the experimental cohort, one patient was completely asymptomatic, four patients were oligosymptomatic infection, and just one had mild-moderate infection versus 4 oligosymptomatic and 5 mild-moderate infection in the control group. We observed also a reduction in time to nasopharyngeal swab negativization. No adverse events were reported in our data. We collected the dosage of anti-Receptor-Binding Domain (RBD) SARS-CoV2 spike protein for 21 patients, revealing adequate seroconversion in 12 patients out of 21; (4) Conclusions: Even though the study was conducted during the Omicron wave, notably known to be less responsive to monoclonal antibodies, we proved that TGM-CGM could be a risk-free additional tool to prevent SARS-Cov2 infection in rheumatic immunosuppressed patients.

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

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

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

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

Multisystem inflammatory syndrome related to SARS-CoV-2 infection (MIS-C) is a rare severe illness affecting pediatric patients. No data are available in literature about the presence of SARS-CoV-2 RNA in faeces in patients with MIS-C. The SARS-CoV-2 positivity was evaluated in fecal samples obtained in a prospective cohort of pediatric patients admitted to our tertiary Hos-pital and diagnosed with MIS-C or COVID-19 between April 15, 2020, and February 29, 2021. The real-time RT-PCR was performed using a validated kit. The assay measures 3 target genes: SARS-CoV-2 gene E, gene N, gene ORF1ab. Overall, 16/63 (25%) fecal samples revealed the pres-ence of SARS -CoV-2 RNA. No differences were detected about time from presumptive viral ex-posure and the time of stool collection (14 vs 8 days, p> 0,05) as well as about the presence of gas-trointestinal symptoms (p>0.05) between patients with positive (+) stools for SARS-CoV-2 RNA and patients tested negative (-). Among children with MIS-C, stools were collected 27.5 days as median (95% CI 14-34) after presumed contact and the positivity rate was 12.5% (4/32). According to our data, we could suggest contact precautions with all patients with MIS-C. Further sample collection is ongoing to verify our preliminary data.

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

Sanitisation has become a major component of everyday life, with emphasis on the hands and surfaces. The face remains unsanitised due to the lack of an acceptable sanitiser. The use of masks has been mandated to reduce the spread of the pathogens by covering the face, however, there remain issues with the use of personal protective equipment. The face remains a harbour for upper respiratory tract infections, with constant deposition of microbes. By reducing microbial load, the risk of both infection and severity are reduced. HOCl has proven antimicrobial and anti-inflammatory activity, including efficacy against SARS-CoV-2. A facial sanitiser, alongside hand sanitisers and masks, improves protection against SARS-CoV-2. The advantages of regular sanitising of the face and mask include reduced level of microbial contamination, risk of biofilm formation, and respiratory tract and skin infections. HOCl was reviewed as a face and mask sanitiser, concluding that it was an ideal product.

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

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

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

(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: Recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.

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

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.

The dynamical equations of the susceptible-infected-recovered/removed (SIR) epidemics model play an important role to predict and/or analyze the temporal evolution of epidemics outbreaks. Crucial input quantities are the time-dependent infection ($a(t)$) and recovery ($\mu (t)$) rates regulating the transitions between the compartments $S\to I$ and $I\to R$, respectively. Accurate analytical approximations for the temporal dependence of the rate of new infections $\dot{J}(t)=a(t)S(t)I(t)$ and the corresponding cumulative fraction of new infections $J(t)=J(t_0)+\int_{t_0}^tdx\dot{J}(x)$ are available in the literature for either stationary infection and recovery rates and for a stationary value of the ratio $k(t)=\mu (t)/a(t)$. Here a new and original accurate analytical approximation is derived for general, arbitrary and different temporal dependencies of the infection and recovery rates which is valid for not too late times after the start of the infection when the cumulative fraction $J(t)\ll 1$ is much less than unity. The comparison of the analytical approximation with the exact numerical solution of the SIR-equations for different illustrative examples proves the accuracy of the analytical approach.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

Objective: On March 11, 2020 the WHO declared that COVID-19 is pandemic. Among the risk factors for many infectious diseases, a role of the ABO blood group system is reported in the literature. We argue whether it is necessary to investigate the relationship between ABO blood groups and susceptibility to SARS-CoV-2 infection and if we should consider some blood groups as potential risk factors for COVID-19. Results: Based on the scientific evidence reported in this letter, we believe that further studies are needed to investigate how the ABO polymorphism influences the host susceptibility, individual response and clinical risk for SARS-CoV-2 infection.

The SARS-CoV-2 high infectivity is due to the functional polybasic furin cleavage site in the S protein. How it was acquired is unknown. There are two challenges to face: (i) an evolutionary model, to fit the origin of the coronavirus; and (ii) a molecular mechanism for the site acquisition. Here we show genomic fingerprints which are specific of Pangolin-CoVs, Bat-SARS-like (CoVZC45, CoVZXC21), bat RatG13 and human SARS-CoV-2 coronaviruses. This, along with phylogenetic analysis, we found that these species have the same evolutionary origin in the bat, including a genetic recombination of S gene between Pangolin-CoV (2017) and RatG13 ancestors. However, this does not explain why SARS-CoV-2 is the only of them with the furin site, which consists in four amino acid (PRRA) motif. The Arginine doublet is encoded by CGGCGG codons. Surprisingly, none of the Arginine doublet of other furin site of viral proteins from several type of viruses, are encoded by the CGGCGG codons. This makes it difficult to consider a virus recombination as mechanism for the PRRA acquisition. The origin of SARS-CoV-2, is the origin of the recognition cleavage site. The bat coronavirus RaTG13 appears to be the closest relative of the SARS-CoV-2, but was isolated in 2013. So, new RatG13 samples would provide insights into the acquisition of the polybasic motif.

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

Background: Vaccinating children against COVID-19 is an essential public health approach for preventing infection in children and adults. This study aimed to explore parents' attitudes toward and the rate of COVID-19 vaccine hesitancy among children in Oman. Methods: This cross-sectional study used an online, self-administered questionnaire. The 9-item questionnaire was validated earlier and administered between June 2021 and May 2022. Multiple logistic regression was used to determine the factors associated with vaccine hesitancy. The parents received a pre-validated Google questionnaire. Responses from the parents of children younger than 11 years of age were accepted. Results: 384 participants completed the questionnaire, including 207 males (54%). The response rate was 86% (384/447). Of the 384 participants, 69% of the parents hesitated to vaccinate their children aged 1-11-year-old children). In parents of children aged 1–4 years, parental vaccination status was significantly associated with vaccine hesitancy (odds ratio [OR]: 0.116, 95% confidence interval [CI]: 0.044–0.306; p < 0.001). Additionally, vaccine hesitancy was significantly more common in mothers than in fathers (OR: 0.451, 95% CI: 0.240–0.848; p = 0.013). . Mothers of children were 77% more likely to be hesitant than fathers (.78, 95% confidence intervals (CI) = 0.50–0.1.23; p = 0.283). Conclusion: Many parents hesitated to vaccinate their children against COVID-19. Consequently, future awareness campaigns and strategies should target new vaccines. The results of our study show that the Arabic version of the 5-point Likert Scale for Vaccination Hesitancy is a valid and reliable tool.

SARS-CoV-2 was identified as the pathogenic agent causing the COVID-19 pandemic. Among the proteins codified by this virus, the Spike is one of the most external and exposed. A fragment of the Spike protein, named the Receptor Binding Protein (RBD) interacts with the ACE2 receptors of human cells, allowing the entrance of the viruses. RBD has been proposed as an interesting protein for the development of diagnosis tools, treatment and prevention of the disease. In this work, a method for recombinant RBD production using Pichia pastoris as a cell factory in a Stirred Tank Bioreactor (SRTB) up to 7 L was developed. Using a basal saline medium with glycerol, methanol and compressed air in a four stages procedure, around 500 mg/L of raw yRBD (RBD produced by yeasts) and 206 mg/L of purified (>95%) RBD were obtained. Thereby, the proposed method represents a feasible, simple, scalable and cheap procedure for the obtention of RBD for diagnosis kits and vaccines formulation

As reported by us and others previously (1, 2), the D614G mutation appeared in the spike glycoprotein (SPG) of the SARS-CoV-2 (the pathogen behind COVID-19) at the early stages of the pandemic and then G614 containing variant of SARS-CoV-2 became the predominant strain in most human populations across the world. However, one of the most recent reports from India (3) stated the incidence of G614 to be only 26% in the Indian population. This report is contradictory to the information available through the GenBank (4) SARS-CoV-2 sequence deposits made by various laboratories from India. The above stated report currently circulating in the Indian media is likely to create a public perception that the Indian strain is less contagious and such a notion could be harmful to people’s welfare. In view of this concern we have re-evaluated, updated and recalculated the incidence of the G614 variant in the Indian population by analyzing 395 Indian SARS-CoV-2 genomic sequences available in the GenBank as of June 26, 2020. In our analysis we have categorized the samples by the month in which the samples were collected. We have used an alignment-free software tool named Compare (5, 6), and the Basic Local Alignment Search Tool (BLAST) (7) in the present analysis. We finally inspected each of the 395 sequences physically for the presence of aspartic acid (D) or glycine (G) at the 614^th position of the spike glycoprotein. We analyzed an Australian cohort in parallel for comparison. We have found that the prevalence of G614 variant in the Indian samples for the month of June 2020 is 90.6%. The trends are similar with the Australian samples.

This paper reports the design, development, and testing of a novel, yet simple and low-cost portable device for the rapid detection of SARS-CoV-2. The device performs loop mediated isothermal amplification (LAMP) and provides visually distinguishable images of the fluorescence emitted from the samples. The device utilises an aluminium block embedded with a cartridge heater for isothermal heating of the sample and a single-board computer and camera for fluorescence detection. The device demonstrates promising results within 20 minutes using clinically relevant starting concentrations of the synthetic template. Time-to-signal data for this device are considerably lower compared to standard qPCR machine (~10-20 minutes vs &gt;38 minutes) for 1×105 starting template copy number. The device in its fully optimized and characterized state can potentially be used as simple to operate, rapid, sensitive, and inexpensive platform for population screening as well as point-of-need SARS-CoV-2 detection and patient management.

Introduction: The SARS-CoV-2/COVID-19 pandemic has triggered the need for developing rapidly effective and safety vaccines to prevent infection, particularly in those at-risk populations such as medical personnel. The objective of this study was to assess perception of COVID-19 vaccination amongst Colombian physicians featuring two different sceneries of COVID-19 vaccination. Methods: A cross-sectional analytical study was carried out through an online survey, directed at medical staff in several cities in Colombia. The percentage of physicians who have a positive perception to be vaccinated and the associated factors that determine that decision were determined. A binomial regression analysis adjusted for age and sex was carried out, taking as a dependent variable the acceptance of free vaccination with an effectiveness of 60 and 80%. The most significant factors were determined in the non-acceptance of vaccination. Results: Between 77.1% and 90.8% of physicians in Colombia, accept COVID-19 vaccination, according to the scenario evaluated where the effectiveness of the vaccine was 60 or 80%, respectively. Medical specialty, have ever paid for a vaccine, recommend administrating the vaccine to their parents or people over 70 years and dispense the vaccine to their children were the factors to be vaccinated for free with an effectiveness of 60% and 80%. Conclusions: There is a high perception of the intention to vaccinate physicians in Colombia against COVID-19. But it is very similar to that of the general population, according to results reported in other studies.

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

Objectives: As institutions modified medical practices to mitigate the spread of the SARS-CoV-2 virus, providers were forced to modify care through the implementation of telemedicine. The objective of this article is to review the current practices of otolaryngology during the COVID-19 pandemic and the limitations of telemedicine in current practice. Methods: A thorough review of the PubMed and MEDLINE databases was performed for publications between 2020 and 2021. Studies discussing telemedicine in otolaryngology during COVID-19 pandemic were selected. Results: As worldwide cases of COVID-19 continue to oscillate, we must continue to be vigilant in our clinical practice, implementing safe techniques to mitigate the spread of the SARS-CoV-2 virus through the continual use of telemedicine in all specialties of otolaryngology. Trends of increased patient acceptance of the use of telemedicine have been seen across subspecialities, including otolaryngology. Conclusion: Currently there are challenges associated with the implementation of telemedicine in the field of otolaryngology that rely heavily on adjunct physical examination, imaging studies, and specialty procedures. However, telemedicine has tremendous potential and can be adapted to include in the otolaryngologist’s toolbelt during public health emergencies such as the COVID-19 pandemic.

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

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

The world is facing a major health crisis, the global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus, for which no approved antiviral agents or vaccines are currently available. Here we describe a collection of codon-optimized coding sequences for SARS-CoV-2 cloned into Gateway-compatible entry vectors, which enable rapid transfer into a variety of expression and tagging vectors. The collection is freely available via Addgene. We hope that widespread availability of this SARS-CoV-2 resource will enable many subsequent molecular studies to better understand the viral life cycle and how to block it.

Regardless of the SARS-CoV-2 pandemic containment, it remains paramount to comprehensively understand its underlying mechanisms to mitigate potential future health and economic impacts, comparable to those experienced throughout the course of the pandemic. The angiotensin-converting enzyme 2 (ACE2) provide anchorage for SARS-CoV-2 binding, thus implicating that ACE and ACE2 might contribute to the variability in infection severity. This study aimed to elucidate predisposing factors influencing the disease course among people infected by SARS-CoV-2, focusing on angiotensin-converting enzyme (ACE) and ACE2 polymorphisms. Notably, despite similar demographics and comorbidities, COVID-19 patients exhibit substantial differences in prognosis. Genetic polymorphisms in ACE and ACE2 have been implicated in disease progression, prompting our investigation into their role in COVID-19 evolution. Using next-generation sequencing (NGS), we analyzed ACE and ACE2 genes in a sample group comprising six subjects infected by SARS-CoV-2. Our findings revealed a correlation between specific polymorphisms and COVID-19 outcomes. Specifically, ACE and ACE2 intronic deletions were observed in all deceased patients, suggesting a potential association with mortality. These results highlight the significance of genetic factors in shaping the clinical course of COVID-19, emphasizing the importance of further research into the impact of genetic variations on COVID-19 severity.

Abstract: (1) Background: After the COVID-19 pandemic, there is increasing concern regarding the immunity of population to SARS-CoV-2 variants, particularly the Omi-cron variant and its sub-lineages. (2) Methods: The study involved analyzing the im-mune response and symptomatology of 27 vaccinated individuals who were subse-quently infected by Omicron sub-lineages. Blood samples were collected for serological analysis, including the detection of IgG antibodies reactive to the Nucleocapsid (N) and Spike (S) antigens of SARS-CoV-2. Additionally, participants were interviewed to assess the intensity of symptoms during the infection. (3) Results: Despite the high levels of anti-Spike IgG observed after vaccination, all participants were infected by Omicron sub-lineages. The most common symptoms reported by participants were fever or chills, sore throat, and cough. Surprisingly, the levels of anti-Spike IgG found prior to infection did not correlate with symptom severity post-infection. However, it was observed that high post-infection anti-Nucleocapsid IgG levels correlates with mild symptoms during the course of the disease, suggesting a potential role for anti-N antibodies in disease resolution. (4) Conclusions: The high levels of IgG anti-Spike resulting from vaccination may not provide complete protection against infection by the Omicron variant. Addi-tionally, our data suggest that anti-Nucleocapsid IgG titers are negatively correlated with the intensity of the symptoms during mild infections. These findings underscore the importance of ongoing surveillance of viral variants and continuous adaptation of vaccination strategies to ensure efficacy against SARS-CoV-2 variants.

Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019 and has since spread worldwide, is the latest human pandemic, and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented.

The unprecedented COVID-19 pandemic posed major challenges to local, regional, and global economies and health systems, and fast clinical diagnostic workflows were urgently needed to contain the spread of SARS-CoV-2. Here, we describe the platform and workflow established at the Cornell COVID-19 Testing Laboratory (CCTL) for high-throughput testing of clinical samples from the university and the surrounding community. This workflow enabled efficient and rapid detection, and successful control of SARS-CoV-2 infection on campus and its surrounding communities. Our cost-effective and fully automated workflow enabled testing of over 8,000 pooled samples per day and provided results for over 2 million samples. Automation of time- and effort-intensive sample processing steps such as accessioning and pooling increased laboratory efficiency. Customized software applications were developed to track and store samples, deconvolute positive pools, track and report results and for workflow integration from sample receipt to result reporting. Additionally, quality control dashboards and turn-around time tracking applications were built to monitor assay and laboratory performance. As infectious disease outbreaks pose a constant threat to both human and animal health, the highly effective workflow implemented at CCTL could be modeled to establish regional high-capacity testing hubs for infectious disease preparedness and emergency response.

Cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been well-identified since the beginning of the current coronavirus disease 2019 (COVID-19) pandemic. Such conditions can occur of various etiologies, such as respiratory failure and hypoxemia, direct cardiac tissue damage due to viral replication, indirect myocarditis as systemic inflammation, and the interaction of different medications. Recently, with the start of the COVID-19 vaccination programs, COVID-19 vaccine-associated cardiac adverse events (AEs) have emerged and are increasingly being reported. Although these AEs are usually mild and self-limited, they can sometimes cause severe, catastrophic outcomes. This review compares the pathophysiology, diagnosis, and treatment of the de novo SARS-CoV-2 infection-related and COVID-19 vaccine-related myocarditis and pericarditis.

While vaccines are a well-established method of controlling the spread of infectious diseases, vaccine hesitancy jeopardizes curbing the spread of COVID-19. Through the Vaccine Information Network (VIN), this study explored barriers and motivators to COVID-19 vaccine uptake. We conducted 18 focus group discussions with male and female community members, stratified by country, age group, and—for Zimbabwe only—by HIV status. Participants’ median age across both countries was 40 years (interquartile range of 22–40) and most (65.9%) were female. We conceptualized the key themes within the World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE) 3Cs (convenience, confidence, complacency) vaccine hesitancy model. Barriers to vaccine uptake—lack of convenience, low confidence, and high complacency—included inaccessibility of vaccines and vaccination sites, vaccine safety and development concerns, and disbelief in COVID-19’s existence. Motivators to vaccine uptake—convenience, confidence and low complacency—included accessibility of vaccination sites, user-friendly registration processes, trust in governments and vaccines, fear of dying from COVID-19 and knowing someone who had died or become infected with COVID-19. Overall, vaccine hesitancy in South Africa and Zimbabwe was influenced by inconvenience, a lack of confidence, and high complacency around COVID-19 vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cell receptor angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert its fusiogenic activity, the spike protein is typically processed at a specific site (S1/S2 site) by cellular proteases such as furin. The C488 residue, located at the spike–ACE2 interacting surface, is critical for the fusiogenic and infectious roles of the SARS-CoV-2 spike protein. We further demonstrated that the C488 residue of spike protein is involved in subcellular targeting and S1/S2 processing. C488 mutant spike localization to the Golgi apparatus and cell surface were impaired. Consequently, the S1/S2 processing of the spike protein, probed by anti-Ser-686-cleaved spike antibody, markedly decreased in C488 mutant spike proteins. Moreover, brefeldin A-mediated endoplasmic reticulum-to-Golgi traffic suppression also suppressed spike protein S1/S2 processing. As brefeldin A treatment and C488 mutation inhibited S1/S2 processing and syncytia formation, the C488 residue of spike protein is required for functional spike protein processing.

Gal-3BP is a multifunctional glycoprotein involved in cell-cell and cell-matrix interactions known to be upregulated in cancer and various viral infections, including HIV-1, HCV and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP’s complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of IFN and pro-inflammatory cytokines, including interleukin-6, mainly interacting with galectin-3, targeting TRAF-6 and TRAF-3 complex, thus having a putative role in the modulation of TGF-β signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.

Background. A previous study demonstrated the performance of the Salivette® (SARSTEDT, Numbrecht, Germany) as a homogeneous saliva collection system to diagnose COVID-19 by RT-qPCR, notably for symptomatic and asymptomatic patients. However, for convalescent patients, the corroboration of molecular detection of SARS-CoV-2 in paired nasopharyngeal swabs (NPS) and saliva samples was unsatisfactory. Objectives. The aim of the present work was to assess the concordance level of SARS-CoV-2 detection between paired sampling of NPSs and saliva collected with Salivette® at two time points, with ten days of interval. Results. A total of 319 paired samples from 145 outpatients (OP) and 51 healthcare workers (HW) were collected. Due to significant waiting rate at hospital, most of the patients ate and/or drank in waiting their turn. Consequently, a mouth washing was systematically proposed prior saliva collection. None of the HW were diagnosed SARS-CoV-2 positive using NPS or saliva specimens at both time points (n=95) by RT-qPCR. The virus was detected in 56.3% (n=126/224) of the NPS samples from OP, but solely 26.8% (n=60/224) of the paired saliva specimens. The detection of the internal cellular control, the human RNase P, in more than 98% of the saliva samples, underlined that the low sensitivity of saliva specimens (45.2%) for SARS-CoV-2 detection was not attributed to an improper saliva sample storing or RNA extraction. Conclusions. Then, the mouth washing decreased viral load of buccal cavity conducting to impairment of SARS-CoV-2 detection. Viral loads in saliva neo-produced appeared insufficient for molecular detection of SARS-CoV-2. At the time that saliva tests could be a rapid, simple and noninvasive strategy to assess on large scale schooled children in France, the determination of the performance of saliva collection become imperative to standardize procedures.

Alcoholism is a condition associated with psychiatric and psychiatric problems, where the respiratory system is damaged through the mucociliary ladder mechanism and alveolar macrophage dysfunction. In the time COVID-19 has been observed a dramatic increase in alcohol consumption mediated by levels of anxiety and situations of confinement. In this work we analyze the relationship between alcoholism and SARS, especially with SARS-CoV-2, explained by a degradation of the host defenses of the respiratory epithelium by changing the barrier function, the discharge of cytokines and the functions of the cilia. All of them involved in the defense mechanism. of the lungs. This leads to a worse prognosis for patients precisely because of alcohol consumption. Based on this approach, alcoholism will exacerbate the consequences of COVID-19.

We report the first detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from a dog in Connecticut during February 2021. Complete genome sequencing and phylo-genetic analysis of the hCoV-19/USA/CT-CVMDL-Dog-1/2021 (CT_Dog/2021) virus were con-ducted to identify the origin and lineage of the virus. The CT_Dog/2021 virus belonged to the GH/B1.2. genetic lineage and was genetically close to SARS-CoV-2 identified from humans in the U.S. during the winter of 2020-2021. However, it was not related to other SARS-CoV-2 identified from companion animals in the U.S. It contained both D614G in spike and P323L in nsp12 substitutions which have become the dominant mutations in the United States. The continued sporadic detections of SARS-CoV-2 in companion animals warrant public health concerns about their potential to become a new reservoir species of SARS-CoV-2.

Angiotensin-converting enzyme 2 (ACE2) is an important player of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II into angiotensin (1-7). While expressed on the surface of human cells, such as lung, heart, kidney, neurons, and endothelial cells (EC), ACE2 is the entry receptor for SARS-CoV-2. Here, we would like to highlight that ACE2 is predominant on the EC membrane. Many of coronavirus disease 2019 (COVID-19) symptoms have been associated with the large recruitment of immune cells, directly affecting EC. Additionally, cytokines, hypoxia, and complement activation can trigger the activation of EC leading to the coagulation cascade. The EC dysfunction plus the inflammation due to SARS-CoV-2 infection may lead to abnormal coagulation, actively participating in thrombo-inflammatory processes resulting in vasculopathy and indicating poor prognosis in patients with COVID-19. Considering the intrinsic relationship between EC and the pathophysiology of SARS-CoV-2, EC-associated therapies such as anticoagulants, fibrinolytic drugs, immunomodulators, and molecular therapies have been proposed. In this review, we will discuss the role of EC in the lung inflammation and edema, in the disseminate coagulation process, ACE2 positive cancer patients, and current and future EC-associated therapies to treat COVID-19.

The novel coronavirus named by WHO and Coronavirus Study Group (CSG) as SARS-COV-2 is the etiological agent of the newly emerged Coronavirus disease (COVID-19). COVID-19 has become a pandemic threat as the WHO declared it a public health emergency of international concern. Early and precise detection of the virus is important for effective diagnosis and treatment. Various testing kits and assays, including real-time reverse Transcriptase PCR, thermal screening guns, ELISA-based immunoassays, and Point-of-Care (POC), have been implemented or are being explored to detect the virus and/or characterise cellular and antibody responses to the infection. However, these approaches have inherent limitations such as non-specificity, high cost, characterize by long turnaround times for test results, and can be labour intensive. Aptamers, which are single-stranded oligonucleotides, generated artificially by SELEX (Evolution of Ligands by Exponential Enrichment) may offer the capacity to generate high affinity bioprobes for monitoring relevant SARS-COV 2 and COVID-19 biomarkers. This article discusses the prospects of implementing aptasensing technologies for rapid point-of-care detection of SARS-COV-2.

The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatic tools and resources, and advocate for greater openness, interoperability, accessibility and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a clear and present need for a fit-for-purpose, open source SARS-CoV-2 contextual data standard. As such, we have developed an extension to the INSDC pathogen package, providing a SARS-CoV-2 contextual data specification based on harmonisable, publicly available, community standards. The specification is implementable via a collection template, as well as an array of protocols and tools to support the harmonisation and submission of sequence data and contextual information to public repositories. Well-structured, rich contextual data adds value, promotes reuse, and enables aggregation and integration of disparate data sets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19.

The pandemic respiratory disease COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan in December 2019 and then spread throughout the world; Italy was the most affected European country. Despite the close pet-human contact, little is known about the predisposition of pets to SARS-CoV-2. Among these, felines are the most susceptible. In this study, a domestic cat with clear symptoms of pneumonia, confirmed by Rx imaging, was found to be infected by SARS-CoV-2 using quantitative RT–qPCR from a nasal swab. This is the first Italian study reporting on the request of the scientific community to focus attention on the possible role of pets as a SARS-CoV-2 reservoir. An important question remains unanswered: did the cat die from SARS-CoV-2 infection?

This paper is purposed to delineate the current situation around Bangladesh as well as impacts of Coronavirus Disease-2019 (COVID-19) around the country and how the people over here are encountering this threatening pandemic. COVID-19 is an international epidemic that has got rapid wide-spread throughout different countries of the world to date. After its first outbreak in China different continents started to make sense and get aware against COVID-19 though, due to its special strategy of transmission several countries have been quite deteriorated preventing it. All the countries are moving at their best forward to find out any solution so that whole world could get rid of this horrifying situation as soon as possible. The authors here have reported an overview of how the outbreak of COVID-19 had put its commence in Bangladesh and to date how people over here have been tracing the way to tackle this havoc. Also, the changes that have brought around due to the crisis have offered us some fertile lessons that are enunciated here by the authors. To conclude, special considerations are anticipated to be highlighted pertaining COVID-19 outbreak in Bangladesh.

Background: The question of whether children are less likely to pass on SARS-CoV-2 is important for planning society’s response to the pandemic. A document available on the Charité hospital website has not been formally published but is frequently referred to as supporting the notion that viral loads are similar in children and adults. Methods: The summary data from this document was extracted and used to produce summary statistics for three age groups: younger children (ages up to 11), older children (ages 12 to 19) and adults (ages 20 and above). Viral loads between the two children’s groups and the adult group were compared using Welch’s t test, which only requires group means and standard deviations and which is robust against moderate departures from normality. Findings: Viral loads were significantly lower than in adults for both younger children (p=0.04) and older children (p=0.04). Overall, viral loads were lower in children than adults (p=0.005). Interpretation: For both younger and older children, on average those with detectable SARS-CoV-2 have significantly lower viral loads than adults. Funding: No funding was received for this analysis.

Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A drammatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this first part of the review about Cov2 in aged people, we searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We sed them as a paradigm with the purpose to retrieve pathogenetic mechanisms in common among these pathological conditions and SARS-CoV-2 infection, as well as the alteration induced in immune system function by this virus, or by its homologous SARS-CoV. Results: SARS-CoV-2 infection induces an important immune system dysfunction with the development of an exhuberant proinflammatory response in the host, and with the development of a life-threatening condition defined as Cytokine Release Syndrome (CRS). This leads to the Acute Respiratory Syndrome (ARDS), mainly in the aged people. High mortality and lethality rates have been observed in the elderly subjects with CoV-2-related infection. Conclusion: These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS- CoV-2 infection.

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2); ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019 (COVID-19). Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2 soonest. The author recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author recommends more trials for interferons to be tested against SARS CoV-2 especially in severe and critical cases.

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread so rapidly and severely affected the people of almost every country in the world. The highly contagious nature of this virus makes it difficult to take control of the present pandemic situation. With no specific treatment available, the coronavirus disease 2019 (COVID-19) presents a threat to people of all ages including the elderly people and people with other medical complications as a vulnerable group to this disease. Better understanding of viral pathogenesis, appropriate preventive measures, early diagnosis and supportive treatments of the infected patients are now the general solutions to fight against this viral transmission. But, as an emerging disease, most about it remains still poorly understood. This article holds an overview on the origin and structure, pathogenesis, diagnosis and possible therapeutic options for the causative agent, SARS-CoV-2 and disease, COVID-19. However, few therapeutic options, laboratory experiments and other strategies proposed here need to be further clinically tested.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

Next generation sequencing (NGS) from SARS-CoV-2-positive swabs collected during the last months of 2022 revealed a large deletion between ORF7b and ORF8 (426 nt) in six patients infected with the BA.5.1 Omicron variant. This extensive genome loss removed a large part of these two genes, maintaining in frame the first 22 aminoacids of ORF7b and the last 3 aminoacids of ORF8. Interestingly, the deleted region was flanked by 2 small repeats, likely involved in the formation of a hairpin structure. Similar rearrangements, comparable in size and location to the deletion, were also identified in 15 sequences in the NCBI database. In this group, 7 out of 15 cases from the USA and Switzerland presented both the BA.5.1 variant and the same 426 nuclotides deletion. It is noteworthy that 3 out of 6 cases were detected in patients with immunodeficiency and is conceivable that this clinical condition could promote the replication and selection of these mutations.

The COVID-19 pandemic has brought marked changes worldwide to the management of airborne infectious diseases. It sparked the development of the SARS-CoV-2 vaccine and pharmacotherapeutics to prevent infection and increase the survival rate during the acute viral phase and the comorbidities associated with COVID-19. Periodontal disease may increase the morbidity and perhaps the mortality of a COVID-19 infection. However, the molecular interaction between periodontitis and COVID-19 infection remains undetermined. A potential pathogenic co-morbidity may involve periodontal pathogenic release of destructive cytokines in the highly inflamed connective tissue and risk for COVID-19. Additional biomarkers such as C-reactive proteins appear to play a role for risk and pathogenesis of COVID-19. The potential of herpesviruses, especially as it is related to aggressive periodontitis may also be a comorbidity for COVID-19. This paper reviews available evidence on the bidirectional association between periodontitis and COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the COVID-19 pandemic still able to infect the population in many countries. The Omicron strain is the most mutated variant of SARS-CoV-2. The high transmissibility of the strain and the ability to evade immunity require a priority study of its properties in order to quickly create effective means of preventing it. The present work is devoted to the study of in silico interaction of piRNAs with the genome of the SARS-CoV-2 (gRNA) in order to identify endogenous piRNAs and propose synthetic piRNAs with high antiviral activity for drug development. The studies were carried out using proven bioinformatic methods of interaction of the entire SARS-CoV-2 genome with more than eight million piRNAs. Binding sites (BSs) of piRNAs in the 5'UTR were located with overlapping nucleotide sequences called clusters of BSs. Several clusters of BSs were found in the nsp3, nsp7, RNA-dependent RNA polymerase, endoRNAse, S surface glycoprotein, ORF7a and nucleocapsid. 16 synthetic piRNAs have been proposed that interact with gRNA with free binding energy from -170 kJ/mol to -175 kJ/mol, which can be used to create drugs that suppress the reproduction of SARS-CoV-2.

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, viral RNA extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, Soap powder (1.60 x 104, 1.04 x 103), Soap powder and Lysoform® (1.60 x 104, 1.04 x 103) and Alcohol 70% (1.02 x 103, 5.91 x 101) respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51759, p 0.05). In conclusion the sodium hypochlorite role on cloth masks disinfection may also have implications for future health emergencies as well as recommended by WHO.

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

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

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