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

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC₅₀ value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

The recent outbreak of coronavirus disease 2019 caused by the new coronavirus, SARS-CoV-2, has become an international emergency. Since there is no effective therapy for the treatment of this disease, drugs or vaccine that can prevent or cure the SARS-CoV-2 infection are urgently needed. The viral 3-chymotrypsin-like cysteine protease (3CLpro), which plays a key role in the replication of coronavirus, is a potential drug target for the development of anti-SARS-CoV-2 drugs. With the crystal structure of 3CLpro, we performed virtual screening from a small chemical library of a Traditional Chinese Medicine recipe- FuFang Zhenzhu Tiaozhi (FTZ). Five compounds with the best scores were screened and could be considered as potential hit compounds to be investigated further with bioassays for their anti-virus effects.

Violence against healthcare workers (HCWs) is a widespread, underreported and inadequately prevented problem. Only a few companies have efficient systems for assessing the extent of the phenomenon. In 2005, the health surveillance service of a public health company introduced a system that monitored violence experienced by HCWs by means of three items from the Violent Incident Form (VIF), integrated with departmental in-depth analyses using the participatory ergonomics group technique. In 2005, the annual rate of physical assaults was 8.2%, that of threats 12.0%, while the harassment rate was 19.6%. Over the past twenty years of observation (2005-2024), the percentage of workers who reported experiencing a physical attack in the previous year at their periodic medical examination, has fluctuated between 5.8% and 11.1%, except for the years 2020 and 2021 when, during the COVID-19 pandemic, the rate was 3.9% and 3.2%, respectively. During the same pandemic period, the annual threat rate that ranged from 9.4% to 20.1%, dropped to 7.7%, while the prevalence of harassment, that was between 13.5 and 19.6, fell to 7.2%. HCWs believe that (i) limiting visitor access (ii) a better balance of the demand for services and (iii) a better attitude towards HCWs were the causes of the reduced rate of violence during the pandemic. Recording the violence experienced during health surveillance is an economical, reliable and sustainable risk assessment method.

Measuring host communities' perceptions and attitudes towards tourism development has been increasingly common since the mid-1970s. The greater the growth of the tourism industry worldwide, the more relevant it has become to assess the impact of tourism activity on the local residents. In this paper we present the results of a study carried out in two EU countries highly dependent on tourism act though at a different stage of development. Our findings are based on qualitative and quantitative data obtained via a questionnaire survey designed in pre-covid 19 times to analyze the perceptions and attitudes of tourism college students from Croatia and Spain, today’s tourism employers and employees, towards tourism development in sun and sea desti-nations. Our aim is to contrast the hypothesis that the nationality of our sample is a significant variable when evaluating the socioeconomic and environmental impact of the development of the tourism industry. Croatia’s workforce, the most highly dependent on the EU travel and tourism industry show to be much more aware of the negative impacts of tourism development than their Spaniards counterparts; showing a tourism workforce more reluctant to further tourism development.

This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection while computational biology and machine learning have advanced methodologies of predicting virus-host gene and protein interactions. Particular focus is given to interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to resolution of questions regarding the pathogenesis of PASC.

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

SARS-CoV-2 infection remains a global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood including the kinetics of formation of genomic RNA (gRNA), sub-genomic RNA (sgRNA) and replication centers/organelles (ROs). We employed single-molecule RNA-fluorescence in situ hybridization (smRNA-FISH) to simultaneously detect viral gRNA and sgRNA, immunofluorescence to detect nsp3 protein, a marker for the formation RO, and carried out a time course analysis. We found that single molecules of gRNA are visible within the cytoplasm at 30 minutes post-infection (p.i.). Starting from 2 hr. p.i., most of the viral RNA existed in clusters/speckles, some of which were surrounded by single molecules of sgRNA. These speckles associated with nsp3 protein starting at 3 hr. p.i., indicating that these were precursors to ROs. Furthermore, RNA replication was asynchronous as cells with RNA at all stages of replication were found at any given time point. Our probes detected the SARS-COV-2 variants of concern, and BA.1 strain exhibited slower rate of replication kinetics than the WA1 strain. Our results provide insights into the kinetics of SARS-CoV-2 early post-entry events, which will facilitate identification of new therapeutic targets to early stage replication to combat COVID-19.

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

Covid-19 is one of humanity’s biggest threat in the 21st century with WHO figures reporting 636 million cases and up to 6.6 million deaths globally. SARS-CoV-2, the virus that causes the Covid-19 disease, is characterized by high mutation which contributes to its rapid spread. While several vaccines have been produced to minimize the severity of the coronavirus and diverse treatment regimens have been approved by the US FDA under Emergency Use Authorization (EUA), SARS-CoV-2 viral mutations continue to derail the efforts of scientists as the emerging variants evade the recommended therapies. Nonetheless, diverse computational models exist that offer an opportunity to overcome the barriers involved in developing new drugs. In this review, the focus is on the use of various virtual screening techniques like molecular docking, molecular dynamics simulations, QSAR, pharmacophore modeling, and homology modeling in repurposing SARS-CoV-2 therapeutics. The results have been promising from the computer-aided drug design (CADD) studies in suggesting potential compounds for treatment of Covid-19 and helping in bringing the pandemic under control.

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

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

Background: This work presents Com@Rehab, a technological patient-centred activity for individuals needing a physical rehabilitation approach and with a specific loss of functionality. Within this scope, this paper focuses on the description of the activity in virtual reality (VR), its components, design and user profile, and its versatility and future adaptability regarding different ages, pathologies and rehabilitation contexts. Methods: The VR activity has been customised according to the patient's clinical needs while replicating an activity of daily living, namely showering. In addition, to validate and get feedback on the developed system, a validation questionnaire was applied to a group of healthy individuals to test the efficiency of the technology that supports the VR activity. Results: Preliminary results show that 94% of the participants recommended the experience, the performance of the various components of the system was successfully implemented, participants quickly adhered to the VR technology, and the UI assistant’s functionality should be improved. Conclusion: This solution creates a more effective, interactive, humanised rehabilitation approach based on a Virtual Reality (VR) activity. The Com@Rehab Communication Module improves human-human and human-machine communication while contributing to health literacy.

It is crucial to immediately curb the spread of a disease once an outbreak is identified in a pandemic. An agent based simulator will enable the policymakers to evaluate the effectiveness of different hypothetical strategies and policies with a higher level of granularity. This will allow them to identify the vulnerabilities and asses the threat level more effectively, which in turn can be used to build resilience within the community against a pandemic. This study proposes a PanDemic SIMulator (PDSIM ) which is capable of modeling complex environments while simulating realistic human motion patterns. The ability of PDSIM to track the infection propagation patterns, contact paths, places visited, characteristics of people, vaccination, and testing information of the population, allows the user to check the efficacy of different containment strategies and testing protocols. The results obtained based on the case studies of Covid-19 are used to validate the proposed model. However, it is highly extendable to all pandemics in general, enabling robust planning for more sustainable communities.

Since 2020 COVID-19 has caused serious mortality around the world. Given the ambiguity in es-tablishing COVID-19 as the direct cause of death we first investigate the effects of age and sex upon all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we explore several methods to adjust single year of age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single year of age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 years in both 2020 and 2021. During 2020 (+ COVID-19 but no vac-cination) both male and female population-adjusted deaths were significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during widespread COVID–19 vaccination, however, below age 75 deaths progressively increased. This finding arises from a mix of vaccination and year of age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects for age around puberty were demonstrated where females had higher deaths rather than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may lead to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants in 2020 to 2023, we employ the proportion of total deaths at each age which are potentially due to or ‘with’ COVID-19. The original Wuhan strain, and the Alpha variant show somewhat limited divergence in the age profile with the Alpha variant shifted to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted persons below age 65. The Omicron variants showed significantly lower proportion of overall mortality, with markedly higher relative proportion of deaths above age 65 steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states – although slightly obscured by using age bands rather than single year of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID-variant. Deaths determined as ‘due to’ COVID-19 (as opposed to ‘involving’ COVID-19) in England and Wales were especially over-estimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the year of age specificity of SARS-CoV-2 var-iants are discussed. The question is posed as to whether vaccines based on different variants carry the specific age profile through into the vaccine.

ORF7b-2 is an accessory protein of the SARS-CoV-2 virus of only 43 amino acids. It has been implicated in various functional hypotheses, some of which predict its involvement as a trans-membrane protein. In this study, ORF7b-2 has often been compared to ORF7b-1 of the SARS virus to highlight differences and similarities with a protein that should have a similar biological role. Structural analysis of ORF7b-2 and its electrostatic characteristics show a polypeptide with both ends negatively charged and a diffuse negative charge over the entire structure. Therefore, its behavior in solution is like that of a weak negative polyelectrolyte, more precisely a polyanion with a net charge of – 4 at neutral pH. Its structure was modeled with two different modeling systems, one of which was ab initio. The two best models are similar, as confirmed by the Ramachandran plot, and show a central alpha-helical structure with two disordered and mobile ends. A normal mode analysis characterized the low-frequency dynamic aspects of the protein. The analysis of the structural shows a rigid central segment with mobile and fluctuating extremities, involved in a conformational equilibrium of the helix ↔ coil type. The calculation of the dipole moment shows its vector is not aligned with the main axis of the structure with an outward tilt of 24°. Molecular dynamics simulations were also conducted and the one in water is in good agreement with the previous results. While, the simulation performed by inserting a pre-oriented dimer (OMP) into a solvated lipid showed the low tendency of the protein to solvate in the apolar environment of the membrane. ORF7b-2 also shows a widespread distribution of negative surfaces that dynamically adjust to changes in structural organization. The BioGrid platform's [Biological General Repository for Interaction Datasets] through the BioGrid COVID-19 Coronavirus Curation Project shows a very large number of experimentally proven physical interactions unique to ORF7b-2, some of them with cytoplasmic proteins. These features of ORF7b-2, evaluated together, suggest a remarkable propensity of ORF7b-2 to interact with multiple molecular partners on both an electrostatic and hydrophobic basis. All this makes it unreasonable that the only biological function of this protein should be that exerted as an intramembrane protein.

The product is a centrifugal air extractor, whose objective is to extract the stale air of SARS-CoV-2 or Covid-19 (Coronavirus); designed for civil and commercial use, it works with a single-phase alternating current (AC) motor of 220 (V) and 50 (Hz), with high energy efficiency (EE). Developed under the Design Thinking methodology, by electromechanical simulation using NI Multisim 14.0 software, case design using Cfturbo 2020 R2.0 CAD software, and rapid 3D prototyping with the OverLord Pro printer; with a prototype of the conventional stator winding of a synchronous motor with a two-pole PMSM/IPM single-phase alternating current (AC) field winding and a 4000 (Gauss) ferromagnetic ceramic magnet rotor. Innovating online nº 15 of invention patent nº 381968 by Nikola Tesla, 5/1/1888.One of the objectives is to link the middle level or Technical Schools with the University system (and careers with a Technological profile) through Project B374 located in the Secretariat of Science and Technology (SCyT) of the National University of La Plata ( UNLP), whose title is: “Integrated Management of Design and Innovation. Contributions for a theoretical-conceptual and methodological review” by the Director: Mg. Federico del Giorgio Solfa. Just as links were sought with the Research and Development Laboratory of the Department of Industrial Design (LIDDI-FBA-UNLP) through its Director D.I. Pablo Ungaro and D.I. Ana Bocos. In 2021, the project participated in the INNOVAR National Contest of the Ministry of Science, Technology and Productive Innovation of the Nation (MINCYT), Argentine Republic; in the "Covid-19 Projects" category, having been selected in the catalog of innovative products, won the 1st. "Covid-19 Projects" position of the National Agency for Research and Technological Development and local innovation (R+D+i) dependent on MINCYT.The results showed, according to the analysis of the test bench, that the PMSM/IPM type synchronous motor used in the centrifugal fan, with the innovation of the reactance-inductive control in series plus the capacitor in parallel, reduces the power by 67% (Watts) and active energy consumption (kWh), performing 56% more mechanical work (Joules) on the fluid air (with a 50% reduction in carbon footprint). Which leads us to the following conclusion: it is possible to develop centrifugal fans that save electricity (kWh) without the need to resort to (1) the "Fan Affinity Law", nor (2) the use of variable speed drives (VDF) or frequency (which are devices with complex and expensive electronics). Which would bring an enormous saving of the cost of electrical energy.

Abstract: Our goal is to create point-of-care (POC) strategies that accelerate decision making, increase efficiency, improve outcomes, and enhance standards of care in island communities faced with global warming, rising oceans, population migration, and intensifying weather disasters. We assessed needs in the Bantayan Archipelago and mainland Cebu Province, Visayas Islands, Philippines, to map POC diagnostics, rescue times, and spatial care paths. Significant deficiencies were lack of cardiac troponin testing for rapid diagnosis of acute myocardial infarction, absence of blood gas and pH testing for support of critically ill patients, and geographic gaps prolonging patient transfers and delaying treatment. Strengths comprised primary care that can be facilitated by POC testing, logical inter-island transfers for which decision making and triage could be accelerated with onboard diagnostic testing, and healthcare small-world networks amenable to POC advances, such as pre-hospital testing, that avoid overloading emergency rooms. Healthcare resources must be distributed to archipelago islands, not concentrated in large metropolitan areas inaccessible for emergency interventions. We conclude that a point-of-need focus will help improve public health, decrease disparities in mortality among rural islanders versus urban dwellers, and pave the way for heightened resilience in anticipation of the adverse impact of global warming on vulnerable coastal areas.

Background: Both natural immunity and vaccine-induced immunity to COVID-19 may be useful to reduce the mortality/morbidity of this disease, but still a lot of controversy exists. Aims: This narrative review analyzes the literature about: a) the duration of natural immunity; b) cellular immunity; c) cross-reactivity; d) the duration of post-vaccination immune protection; e) the probability of reinfection and its clinical manifestations in the recovered patients; f) comparisons between vaccinated and unvaccinated in the possible reinfections; g) the role of hybrid immunity; h) the effectiveness of natural and vaccine-induced immunity against Omicron variant; i) comparative incidence of adverse effects after vaccination in recovered individuals vs. COVID-19-naïve subjects. Material and Methods: through multiple search engines we investigated COVID-19 literature related to the aims of the review, published since April 2020 through July 2022, including also the previous articles pertinent to the investigated topics. Results: nearly 900 studies were collected and 238 pertinent articles were included. It was highlighted that the vast majority of individuals after COVID-19 develop a natural immunity both of cell-mediated and humoral type, which is effective over time and provides protection against both reinfection and serious illness. Vaccine-induced immunity was shown to decay faster than natural immunity. In general, the severity of the symptoms of reinfection is significantly lower than in the primary infection, with a lower degree of hospitalizations (0.06%) and an extremely low mortality. Conclusions: this narrative review regarding a vast number of articles highlighted the valuable protection induced by the natural immunity after COVID-19, which seems comparable or superior to the one induced by anti-SARS-CoV-2 vaccination. Vaccination of the unvaccinated COVID-19-recovered subjects may not be indicated. Further research is needed in order to: a) measure the durability of immunity over time; b) evaluate both the impacts of Omicron-5 on vaccinated and healed subjects and of hybrid immunity.

The 2019-2020 Australian bushfires followed by the COVID-19 pandemic brought the significant mental health implications of working in healthcare to the fore. The importance of appropriate support services to ensure the resilience and recovery of healthcare workers has been highlighted. In response to healthcare staff experiences during the bushfires, the SEED Wellness Program was created in 2020 in the Illawarra Shoalhaven Local Health District, in NSW Australia. SEED used a participatory action methodology to engage and collaborate with healthcare staff teams in workplace-based restorative activities. Guided by Practice Theory, this study aimed to identify and describe SEED wellness practices that supported healthcare staff. Thirty-three healthcare workers participated in focus groups or individual interviews between June 2021 and March 2022. The analysis involved inductive thematic individual and collective exploration of SEED practices, including co-analysis with participants. Eight core practices that supported participants’ wellbeing were identified including responsive and compassionate leading, engaging staff at every stage of the recovery process, creating a sense of connection with others, and collective caring. The study found that workplace wellness initiatives are optimised when place-based and grounded in local knowledge, needs, and resources incorporating a collective and supportive team approach. Moreover, to ensure engagement in, and sustainability of these initiatives, both bottom-up and top-down commitment is required.

Hybrid organic-inorganic (dendritic polymer-silica) xerogels containing silver nanoparticles (Ag-Nps) were developed as antibacterial leather coatings. The preparation method is environmentally friendly, based on two biomimetic reactions. Silica gelation and spontaneous (Ag-Np) formation were both mediated by hyperbranched poly (ethylene imine) (PEI) scaffolds of variable Mw (2000-750000). The formation of precursor hydrogels was monitored by dynamic light scattering (DLS). The chemical composition of the xerogels was assessed by Infra-Red Spectroscopy (IR) and Energy-dispersive X-ray spectroscopy (EDS) while the uniformity of the coatings was established by scanning electron microscopy (SEM). Release properties of coated leather samples and overall behaviour in water in comparison to untreated analogs were investigated by UV-Vis spectroscopy. Antibacterial activity was tested towards Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and antibiofilm properties against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Acinetobacter baumannii, Enterococcus faecalis while SARS-Cov-2 clinical isolate was employed for the first estimation of their antiviral potential. Toxicity was evaluated using the Jurkat E6.1-cell line. Finally, water contact angle measurements were implemented to determine the enhancement of the leather surface hydrophilicity caused by these composite layers. The final advanced products are intended for use in medical applications.

ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, has transformed the understanding of many complex illnesses like cancer (1,2) and multiple sclerosis (3,4), by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS. Solve M.E. developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with Long COVID (LC) and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people. The Registry is an invaluable resource because it integrates with a symptom tracking app, as well as a biorepository, to provide a robust and rich dataset that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.

Technological advances such as blockchain, artificial intelligence, big data, social media, geographic information systems represent a building block of the digital transformation that supports the resilience of the food supply chain (FSC) and increases its efficiency. This paper reviews the literature surrounding digitalization in FSCs. A bibliometric and key-route main path analysis was carried out to objectively and analytically uncover the knowledge development in digitalization within the context of sustainable FSCs. The research began with the selection of 2140 articles published nearly over five decades. Then, the articles were examined according to several bibliometric metrics such as year of publication, countries, institutions, sources, authors, and keywords frequency. A keyword co-occurrence network was generated to cluster the relevant literature. Findings of the review and bibliometric analysis indicate that research at the intersection of technology and the FSC has gained substantial interest from scholars. On the basis of keyword co-occurrence network, the literature is focused on the role of information communication technology for agriculture and food security, food waste and circular economy, and the merge of the Internet of Things and blockchain in the FSC. The analysis of the key-route main path uncovers three critical periods marking the development of technology-enabled FSCs. The study offers scholars a better understanding of digitalization within the agri-food industry and the current knowledge gaps for future research. Practitioners may find the review useful to remain ahead of the latest discussions of technology-enabled FSCs. To the authors’ best knowledge, the current study is one of the few endeavors to explore technology-enabled FSCs using a comprehensive sample of journals articles published during the past five decades.

Background: During the COVID-19 pandemic, hygiene behaviors such as keeping distance, avoid-ing masses, wearing face masks and adhering to hand hygiene recommendations became impera-tive. The current study aims to determine factors interrelating with hygiene behaviors. Methods: 4,049 individuals (1,305 male, 2,709 female, aged 18-80 years) were recruited from rehabilitation clinics or freely on the internet and surveyed via online questionnaire between May 2020 and August 2021. Socio-demographics, hygiene behaviors, emotions (fear), life-satisfaction, risk factors and disability as well as communication were assessed. Results: Prevalence for hygiene behaviors was: keeping the distance 84.9%, avoiding mass gatherings 84.6%, wearing face masks 96.5% and hand hygiene 80.7%. Hygiene behaviors were significantly related to fear with linear and quad-ratic associations. Conclusion: Individuals with disabilities, risk factors and psychological symp-toms are more compliant. Especially hand hygiene should be targeted to achieve higher compli-ance rates. A medium level of fear is more functional than too elevated fear. Behavioral interven-tions and targeted communication aiming at improving different behaviors in orchestration can help individuals to remain healthy and maintain a high life-satisfaction. Thereby, communication in the healthcare setting is imperative and all involved individuals should become more aware of this to ensure high hygiene standards and patient safety.

The COVID-19 pandemic has exposed the inadequacies of the current healthcare system and needs a paradigm change, which is holistic, and community based illustrated by the healing wheel. The present paper proposes that existential positive psychology (PP 2.0) represents a promising approach to meet the rising needs in palliative care. This framework has a twofold emphasis on (a) How to transcend and transform suffering as the foundation for wellbeing, and (b) how to cultivate our spiritual and existential capabilities to achieve personal growth and flourishing. We propose that these objectives can be achieved simultaneously through dialectical palliative counselling, as illustrated by Wong’s integrative meaning therapy (Wong, 2020) and Lo’s Conceptual Model of CALM Therapy in palliative care (Lo et al., 2014). We then discuss existential suffering in general and at the last stage of life in particular; we also review recent research and interventions on existential suffering in palliative patients. Finally, we outline the objectives and the strategies of IMT in providing palliative counselling for palliative care and hospice patients.

A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

To safeguard against meat supply shortages during pandemics or other catastrophes, this study analyzed the potential to provide the average household’s entire protein consumption using either soybean production or distributed meat production at the household level in the U.S. with: 1) pasture-fed rabbits, 2) pellet and hay-fed rabbits, or 3) pellet-fed chickens. Only using the average backyard resources, soybean cultivation can provide 80%-160% of household protein and 0%-50% of a household’s protein needs can be provided by pasture-fed rabbits using only the yard grass as feed. If external supplementation of feed is available, raising 52 chickens while also harvesting the concomitant eggs or alternately 107 grain-fed rabbits can meet 100% of an average household’s protein requirements. These results show that resilience to future pandemics and challenges associated with growing meat demands can be incrementally addressed through backyard distributed protein production. Backyard production of chicken meat, eggs, and rabbit meat reduces environmental costs of protein due to savings in production, transportation, and refrigeration of meat products and even more so with soybeans. Generally, distributed production of protein was found to be economically competitive with centralized production of meat if distributed labor costs were ignored.

One of the critical tools for early detection and subsequent evaluation of the incidence of lung diseases is chest radiography. At a time when the speed and reliability of results, especially for COVID-19 positive patients, is important, the development of applications that would facilitate the work of untrained staff involved in the evaluation is also crucial. Our model takes the form of a simple and intuitive application, into which you only need to upload X-rays: tens or hundreds at once. In just a few seconds, the physician will determine the patient's diagnosis, including the percentage accuracy of the estimate. While the original idea was a mere binary classifier that could tell if a patient was suffering from pneumonia or not, in this paper we present a model that distinguishes between a bacterial disease, a viral infection, or a finding caused by COVID-19. The aim of this research is to demonstrate whether pneumonia can be detected or even spatially localized using a uniform, supervised classification.

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. This suggests a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents.

COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBD_Spike). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction. In this current study, we adopt a protein design approach to predict and propose non-virulent structural mimics of the RBD_Spike which can potentially serve as its competitive inhibitors in binding to ACE2. The RBD_Spike is an independently foldable protein domain, resilient to conformational changes upon mutations and therefore an attractive target for strategic re-design. Interestingly, in spite of displaying an optimal shape fit between their interacting surfaces (attributed to a consequently high mutual affinity), the RBD_Spike–ACE2 interaction appears to have a quasi-stable character due to a poor electrostatic match at their interface. Structural analyses of homologous protein complexes reveal that the ACE2 binding site of RBD_Spike has an unusually high degree of solvent-exposed hydrophobic residues, attributed to key evolutionary changes, making it inherently ‘reaction-prone’. The designed mimics aimed to block the viral entry by occupying the available binding sites on ACE2, are tested to have signatures of stable high-affinity binding with ACE2 (cross-validated by appropriate free energy estimates), overriding the native quasi-stable feature. The results show the apt of directly adapting natural examples in rational protein design, wherein, homology-based threading coupled with strategic ‘hydrophobic ↔ polar’ mutations serve as a potential breakthrough.

Nowadays, the development of civilization requires a vision of balancing the interests of employees and employers in the sphere of work as never before. Work-life balance is directly linked to social sustainability. The aim of this article is to analyse various dimensions of mutual enrichment of the professional and private life of an individual and to describe how positive experiences in professional and non-professional life influence the improvement of satisfaction, health and achievements, thus enabling the sustainable development of the individual. The conducted research was of a qualitative nature. Thematic exploration was used to analyse the findings of 34 in-depth interviews with experienced HR managers and employees at various levels of enterprises in Poland. The research shows that the work and personal life of the respondents interact, complement, and enrich in different ways, depending on the stage of the employee’s life. Habits developed by practicing a specific sport discipline or other type of hobby are helpful in the effective implementation of professional tasks. Also, non-professional interests, including communing with culture and art have a positive impact on professional activities. On the other hand, the respondents emphasized that thanks to their professional activities, specific to the type of work they perform, they are sometimes more extroverted, meticulous, organized and consistent when performing activities outside of work and in other aspects of private life.

Accurate diagnosis at an early stage of infection is essential for the successful management of any contagious disease. The COVID-19, caused by the SARS-CoV-2 virus is a pandemic that has affected 214 countries affecting more than 30.8 million people causing 0.957 million deaths as of third week of September, 2020. The primary diagnosis of the infection is done either by the molecular technique of RT-qPCR by detecting portions of the RNA of the viral genome or through immunodiagnostic tests by detecting the viral proteins or the antibodies produced by the host. As the demand for the test increased rapidly many naive manufacturers entered the market with novel kits and more and more laboratories also entered the diagnostic arena making the test result more error-prone. There are serious debates globally and regionally on the sensitivity and specificity of these tests and about the overall accuracy and reliability of the tests for decision making on control strategies. The significance of the test is also complexed by the presence of asymptomatic carriers, re-occurrence of infection in cured patients as well as by the varied incubation periods of the infection and shifting of the viral location in the host tissues. In this paper, we review the techniques available for SARS-CoV-2 diagnosis and probable factors that can reduce the sensitivity and specificity of the different test methods currently in vogue. We also provide a check-list of factors to be taken care to avoid fallacious practices to reduce false positive and false negative results by the clinical laboratories

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.

Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.

To mitigate the spread of the COVID-19 coronavirus, some countries have enforced more stringent non-pharmaceutical interventions in contrast to those widely adopted (for e.g. the state of Kuwait). In addition to standard practices such as enforcing curfews, social distancing, and closure of non-essential service industries, other non-conventional policies such as the total confinement of highly populated areas has also been implemented. In this paper, we model the movement of a host population using a mechanistic approach based on random walks, which are either diffusive or super-diffusive. Infections are realised through a contact process, whereby a susceptible host may be infected if in close spatial proximity of the infectious host. Our focus is only on the short-time scale prior to the infectious period, so that no further transmission is assumed. We find that the level of infection depends heavily on the population dynamics, and increases in the case of slow population diffusion, but remains stable for a high or super-diffusive population. Also, we find that the confinement of homogeneous or overcrowded sub-populations has minimal impact in the short term. Finally, we discuss the possible implications of our findings for total confinement in the context of the current situation in Kuwait.

In the context of the COVID-19 epidemic, and on the basis of the Theory of Dynamical Systems, we propose a simple model for the expansion of contagious diseases, with a particular focus on viral respiratory tracts. The infection develops through contacts between contagious and exposed people, with a rate proportional to contact duration and turnover, inversely proportional to the efficiency of protection measures, and balanced by the average immunological response. The obvious initial exponential increase is readily hindered by the size reduction of the exposed population. The system converges towards a stable attractor whose value is expressed in terms of the ratio C/D of contamination vs decay factors. Decreasing this ratio below a critical value leads to a tipping point beyond which the epidemic is over. By contrast, significant values of C/D may bring the system through a bifurcating hierarchy of stable cycles up to a chaotic behaviour.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected around 1.5 million individuals with a mortality rate ranging from 5 to 10%. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (M^Pro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of M^Pro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae M^Pro in five clusters specific to viral hosts. This clustering was also corroborated with the comparison of M^Pro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 M^Pro. In agreement with this, we performed screening of the custom-made library of ~7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 M^Pro as the primary target. We identified several natural molecules that strongly binds to SARS-CoV-2 M^Pro among which top seven molecules are d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin and Phyllaemblicin B. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp and hACE-2. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.

The COVID-19 pandemic has significantly reshaped global power dynamics, impacting economies, political landscapes, international relations, and technological advancements. Historically, pandemics have acted as catalysts for social and economic transformations, and COVID-19 has followed this pattern by intensifying existing trends and creating new opportunities for power shifts. Economically, the pandemic led to unprecedented disruptions, with East Asian countries demonstrating greater resilience and adaptability compared to Western economies. This has resulted in notable economic power shifts, particularly benefiting China, which experienced a swift recovery. Politically, the pandemic exacerbated geopolitical tensions, notably between the United States and China, while also fostering new forms of international cooperation, such as vaccine diplomacy and multilateral health initiatives. Technologically, the pandemic accelerated digital transformation and innovation in biotechnology, with significant advancements in healthcare systems. Socially, it exposed and exacerbated inequalities, prompting discussions on social justice and healthcare reforms. Environmentally, short-term improvements were observed, but the need for sustainable development and green recovery strategies became evident. This article examines these shifts, highlighting the interconnectedness of global challenges and the necessity for coordinated, multilateral responses to build a more equitable and sustainable future.

Long COVID is the collective term used to describe the persistence of symptoms in individuals who have recovered from SARS-CoV-2 infection. Some people who have healed from COVID-19 continue to experience new or persistent symptoms that last for weeks or months. While Long COVID is becoming more widely recognized, its fundamental causes and effective therapies remain largely unclear. This study aims to explore the potential of phytochemical medications as a cutting-edge therapeutic strategy for treating Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC).G protein-coupled receptors (GPCRs), which play a critical role in cell signaling, were the focus of this study. GPCRs are known to be involved in immunological and inflammatory responses and are considered potential targets for Long COVID therapy. The GPCRs examined included chemokine receptors, serotonin receptors, adrenergic receptors, and histamine receptors. The docking results demonstrated high binding affinity between phytochemical drug structures and these receptors for most drug-receptor combinations.The study consists of three main parts. First, data on receptors and drugs were retrieved from the Protein Data Bank (PDB) and PubChem, respectively. The receptors selected are those predicted to be linked to Long COVID. The structure of the drugs was converted from SDF to PDB format using OpenBabel from ChemInfo. Docking studies were performed to assess the binding affinity between the drugs (ligands) and their respective receptors (binding sites) using iGemDock v2.1.In conclusion, the findings of this study could have significant implications for the development of alternative therapies for Long COVID.

The neurologic effects of long-COVID are a therapeutic challenge. This article discusses the immunologic manifestations of long-COVID and proposes a non-androgenic, synthetic analog of dehydroepiandrosterone (DHEA), bromo-epi-androsterone (BEA), as a candidate for clinical trials for this exigent collection of neurologic conditions. Moreover, because there is an association between long-COVID and Alzheimer’s disease, the evaluation of BEA in long-COVID may serve as a proxy for its effect on neuroinflammatory biomarkers of Alzheimer’s disease that are shared with long-COVID.

A severe consequence of SARS-CoV-2 infection that manifests as systemic inflammation and multi-organ involvement is called Multisystem Inflammatory Syndrome in Children (MIS-C). This review examines the possible relationship between gut barrier integrity, the microbiome, dysregulation of interleukin-6 (IL-6) signaling, and MIS-C. Clinical and biochemical features of MIS-C are similar to those of other hyperinflammatory syndromes, suggesting a dysregulated immune response. One possible explanation for the systemic inflammation seen in MIS-C patients is SARS-CoV-2-induced dysregulation of the IL-6 signaling pathway. In addition, new data suggest a reciprocal link between gut barrier integrity and IL-6. SARS-CoV-2 exhibits bacteriophage-like behavior, highlighting the role of bacteria as a reservoir for the virus and emphasizing the importance of understanding the bacteriophagic mechanism of the virus in fecal-oral transmission. Increased translocation of viral products and bacterial toxins may result from disrupting the intestinal barrier and cause systemic inflammation. On the other hand, systemic inflammation can weaken the integrity of the intestinal barrier, which feeds back into the loop of immunological dysregulation. In the context of MIS-C, understanding the interaction between SARS-CoV-2 infection, IL-6, and gut barrier integrity may shed light on the etiology of the disease and guide treatment options.

For this research we are selected three indicators of wheat: yield (t/ha), producer price (USD/t) and share of the harvested area under wheat in relation to the total land area of country (%). The mentioned indicators were analyzed for the period 2006-2021 in thirty-two European countries. The purpose of the research is to determine which of the mentioned indicators achieve average annual growth/decrease rates, what is the correlation between them, how European countries are grouped with their similarities and differences. The research examines the impact of the COVID-19 pandemic on the mentioned indicators in a two time phases: Phase I, before the pandemic (2006-2019); Phase II, during the pandemic (2020-2021). The methodological approach to the research topic involved the application of descriptive statistics, as the method of principal components analysis (abbr. PCA) with graphics. A positive correlation exists only between the yield of wheat and the share of the harvested area under wheat in the total area of the land (0.291). PCA method showed that countries are grouped differently depending on the observed indicator and the analyzed time phase.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

Estimating the infection risks in indoor environments comprises the assessment of the behavior of virus-laden aerosols, i.e. spreading, mixing, removal by air purifiers etc. A promising experimental approach is based on using non-hazardous surrogate aerosols of similar size, e.g. salt particles, to mimic the virus aerosol behavior. This manuscript addresses the issue how a successful transfer of such experiments can be accomplished. Corresponding experiments in two very different environments, a large community hall and a seminar room, with optional use of air purifiers in various constellations were conducted. While high particle concentrations are advantageous in terms of avoiding influence of background aerosol concentrations, it is shown that appropriate consideration of aggregation and settling are vital to theoretically describe the experimentally determined course of particle concentrations. A corresponding model equation for a well-mixed situation is derived and the required parameters are thoroughly determined in separate experiments independently. It is demonstrated that clean air delivery rates (CADR) of air purifiers determined with this approach may differ substantially from common approaches not explicitly taking into account aggregation.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

A change in biological properties of the SARS-CoV-2 virus can enhance its transmissibility and virulence, complicate the disease course, and reduce the effectiveness of anti-viral therapy and vaccination. We have studied 16 genetic lineages of the Omicron variant. The viral reproduction course was analyzed based on plaque morphology in the agar layer and the maximum titer in Vero E6 cells. BALB/c mice and Syrian hamsters were used as animal models. Viral load and infectious SARS-CoV-2 titer were determined in the nasal tissue and lungs. The severity of infectious process was assessed using histological methods. An increased plug size was observed in CH.1.1 and BQ.1.2.1 strains after six passages. This was due to substitutions D614G, H655Y, and N764K in the coronavirus S protein. The same changes in gene variants Gamma and BA.1 were caused by the substitution R682W, which is not present in lineages CH.1.1 and BQ.1.2.1. A similar substitution, namely R682P, was observed in the BA.5.1 strain. We characterized BA.1 (as a reference), BA.5.2, and XBB.3 strains in vivo as representatives of the main circulating genetic lineages. For the BA.1 strain, ID50 was 1.3 and 14 TCD50 in Syrian hamsters and BALB/c mice, respectively. An insignificant increase in the BA.5.2 virulence compared to that of BA.1 was noted (ID50 was 07. and 10 TCD50, respectively). The XBB.3 pathogenicity in laboratory animals is similar to that of BA.1 (ID50 was 1.8 and 15 TCD50, respectively). Experiments showed a consistent decrease in the virulence of Omicron strains compared to previously circulating SARS-CoV-2 variants. A co-evolutionary change in amino acid sequences, affecting the conformation of the coronavirus S protein and its surface epitopes in representatives of different genetic lineages, was noted. The emergence of potential proteolysis sites and alterations of the furin cleavage site have been observed in numerous Omicron coronavirus variants.

This study delves into the dynamics of relational energy (RE) within organizational context, examining some of its antecedents and decedents. Specifically, it investigates the influence of psychological capital (PsyCap) and humor on RE, and subsequently, the latter’s impact on job performance (JB) mediated by job engagement (JE). A research model based on structural equation modelling carried out with 481 employees in private service industries demonstrates several key relationships. It reveals that both PsyCap and affiliative humor positively affect RE, while aggressive humor exerts a negative influence. Furthermore, RE shows positive association with JE and JP, with JE serving as a mediator. To the authors’ knowledge, this is the first study to present an integrated model encompassing this exact combination of influencers and consequences of RE as well as to be investigated within Western Balkans cultural context. Therefore, it represents a novel approach. Additionally, the research addresses crucial questions regarding the existence and strategic significance of RE within organizational interactions. The findings offer valuable insights for organizations seeking to enhance employee engagement, performance, and wellbeing – even during health crises such as COVID-19 – by fostering RE. The study advances the understanding of RE in organizational settings and provides a foundation for future research in this domain.

Discovery and development of effective strategies to treat emerging and often drug resistant strains of viral and microbial pathogens presents one of the greatest challenges of the 21st century. Despite nearly a century of progress in developments in antimicrobial and antiviral therapies, infectious diseases still account for a substantial proportion of deaths worldwide, including over 100 million globally in the recent pandemic to date. In recent decades, the plague of antimicrobial resistance also represents an additional and alarming signal for both human and animal healthcare and signals a renewed sense of urgency in addressing this issue. This has made the search for novel classes of antibiotics, antivirals and therapeutics found to be capable of bypassing the microbial and viral resistance mechanisms necessary to in order to replenish our current arsenal of antimicrobial and antiviral drugs and update our therapeutic regimens. In addition, the tremendous impact exerted by viral infections and related pathologies on our lives during the recent decade has forced scientists to acknowledge the opportunities and challenges associated with tackling infectious diseases by developing effective antiviral agents endowed with novel mechanisms of action. The discovery of new antimicrobial/antiviral agents, as well as the repurposing of existing drugs and therapeutic options will be crucial to fight the ever-increasing resistance of “superbugs”, pathogenic fungi, viruses, and parasites. Proponents of modern biophoton therapy proposed in this paper can trace its origins to the Russian scientist Alexander Gurwitsch, who a century ago observed ultra-weak emissions of light emerging from an onion root and soon found additional living tissues to be emanating similar energetic phenomena, thus energizing research which continues to the present day and projected toward the development of useful applications of the new-found biological photonic phenomena. The purpose of the present paper is to introduce the past experiences, potential applications and highly successful outcomes of biophotonic therapy as an option to treat infectious diseases including HIV, Hepatitis C, MRSA, and others, with emphasis on efficacy of using biophotonic therapies to treat and ameliorate the drug resistant variants of the above infectious agents, including potential applications for the current COVID-19 pandemic and in preparation for the emergence of the next epidemic or pandemic.

The use of food waste disposers in gastronomical facilities influence the municipal wastewater composition. Ground food waste poses problems in the operation of the sewerage network and generates high electric energy consumption in wastewater treatment plants (WWTP). The study aimed to determine, for five towns with a PE of 4,000 to 220,000, the volumes of catering waste discharged to the WWTPs. The towns differed in the number of inhabitants, beds in hotel and catering places. The calculations were made based on data received from the operators of WWTP. The pollutant concentrations in 2019, were compared with data from the "pandemic" year - 2020. The loads of catering waste entering the sewerage system in 2019 ranged from 32.7 to 1062 tons. In town with the largest tourist base, the BOD value in 2020 accounted for 62.3% of 2019 value. In the largest town, the annual energy consumption for food waste treatment could be up to 2,539,770 kWh. If the waste was fermented, it could be obtained up to 1,376,650 m3 of methane. There is a strong need for implementing a collection system for food waste from catering facilities and its fermentation to produce methane, which can be used for energy purposes.

During COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Basing on previous data on Methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly associated to the intrinsic antimetabolic activity of these drugs, but also to a specific antiviral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, Pralatrexate and Trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.

Mounting evidence supports the connections between exposure to environment types––such as green spaces and biodiversity––and human health. However, the mechanistic links that connect biodiversity (the variety of life) and human health, plus the level of supporting evidence, are less clear. Here, we undertook a scoping review to map the links between biodiversity and human health and summarise the levels of associated evidence using an established weight of evidence framework. Distinct from other reviews, we provide additional context regarding the environment-microbiome-health axis, evaluate the environmental buffering pathway (e.g., biodiversity impacts on air pollution), and draw upon expert opinion to provide case studies on three underrepresented linkages. The case studies include (1) biodiversity and Indigenous Peoples’ health, (2) biodiversity and urban social equity, and (3) biodiversity and COVID-19. We observed a moderate level of evidence to support the environmental microbiota-human health pathway and a moderate-high level of evidence to support broader nature pathways (e.g., green space) to various health outcomes, from stress reduction to enhanced wellbeing and improved social cohesion. However, studies of broader nature pathways did not typically include specific biodiversity metrics, indicating clear research gaps. Further research is required to understand the connections and causative pathways between biodiversity (e.g., using metrics such as taxonomy, diversity/richness, structure, and function) and health outcomes. There are well-established frameworks to assess the effects of broad classifications of nature on human health. These can assist future research in linking biodiversity metrics to human health outcomes. Our case studies on underrepresented linkages highlight the roles of biodiversity and its loss on urban lived experiences, infectious diseases, and Indigenous Peoples’ sovereignty and livelihoods. More research and awareness of these socioecological interconnections are needed.

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platforms research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced Th1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine.

The COVID-19 pandemic is one of the worst catastrophes that we have faced globally in recent years. It has not only taken its toll on the economic sector but also on the education sector. The social distancing norms that are in place as a direct response to the pandemic have turned conventional classroom teaching into a problematic minefield; as such, students all over the world have been forced into unprecedented situations that have served only to worsen the situation. The current pandemic has given rise to one of the worst crises the 21^st Century has ever seen, resulting in a surge of unemployment. Many companies have taken the route of firing employees or making redundancies, as they cannot afford the monthly reimbursement for staff. While this issue primarily concerns full-time workers, it also carries significant consequences for students – a considerable number of students are required to earn their daily living costs, and, without a job, they cannot pay their educational fees, accommodation costs, or living expenses. This comprehensive study briefly discusses the multitude of problems faced by students in the UK regarding higher education, as a direct result of the coronavirus pandemic. It contains six individual sections: a detailed introduction; the methodological procedures employed; educational disruptions, covering issues from hindrances in field research to examinations and student evaluations; personal problems experienced by students, such as accommodation and loss of income; concerns arising from the global pandemic; and finally, a conclusion and summary of the study’s findings.

Background Oil palm (OP), Elaeis guineensis , is by far the most important global oil crop, supplying about 40% of total traded vegetable oil. Palm oils are key dietary components consumed daily by over three billion people, mostly in Asia, and also have a wide range of important non-food uses including in cleansing and sanitising products. Main body Oil palm is a perennial crop with a >25-year life cycle and an exceptionally small land footprint compared to annual oilseed crops. Oil palm crops globally produce an annual 81 million tonnes (Mt) of oil from about 19 million hectares (Mha). In contrast, the second and third largest vegetable oil crops, soybean and rapeseed, yield a combined 84 Mt oil but occupy over 163 Mha of increasingly scarce arable land. Despite this advantage, oil palm has acquired a poor environmental reputation, especially in Europe and North America, although soybean planting is now responsible for more deforestation. Oil palm crops face other challenges in the 2020s. On the demand side, these include changing consumer purchasing habits, threats to global trade systems, and diminishing demand for liquid fuels as transport systems become increasingly electrified. On the supply side, major issues include stagnant yields in ageing plantations, sluggish replanting of improved varieties, labour shortages, diseases and climatic/ environmental threats. The latter include the increasing incidence of new and existing pests/diseases and a general lack of climatic resilience, especially relating to elevated temperatures and increasingly erratic rainfall patterns. This review surveys the oil palm sector in the 2020s and beyond, its major challenges and options for future progress. Conclusions Oil palm crops face many future challenges, including emerging threats from climate change and new pests and diseases, that require more effective international collaboration. Nevertheless, new breeding technologies are providing the promise of improvements, such as much higher yielding varieties, improved oil profiles, enhanced disease resistance and modified crop architecture to enable harvesting mechanisation. The industry also needs to redouble its efforts to engage with global consumers in a constructive dialogue aimed at addressing its image problem and explaining the many benefits of its products.

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

Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease COVID-19, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications like preterm labor and premature rupture of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The ACE2- and TMPRSS2-positive (ACE2+TMPRSS2+) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in ACE2+TMPRSS2+ STBs and EVTs. The ACE2+TMPRSS2+ STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester ACE2+TMPRSS2+ EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry and show that these cells can potentially drive viremia in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections in pregnancy.

We conducted many model simulations to understand the causes of the damages of coronavirus (COVID-19) to lung tissue and constructed a diagram showing apparent viral reproduction, immune response and damage accumulation curves. We found that lung damages include virus-caused damage, tissue damage caused by immune responses and tissue damage caused by accumulated wastes. The virus-caused damage is proportional to the phase lag between the viral reproduction curve and the delayed adaptive immune response curve, while waste-induced damage is attributed to imbalance in removing viral, cellular and metabolic by-products. We found that treatment strategies should slow down viral reproduction and speed up immune response, and improve blood micro-circulation in the lungs. Consistent with the strategies, measures are taken to void direct lung infection, strengthen innate responses, promote immune responses, dilute viral concentration in lung tissue, maintain waste removal balance, protect heart and kidneys, control other infections, avoid allergic reactions and other inflammation, etc. We show that medical, dietary, emotional, lifestyle, environmental, mechanical factors, etc. may be simultaneously used to mitigate lung damages and prove that multiple factor health optimization method is magnitudes more powerful than a single factor treatment. Such a method does not depend on molecular specificity and can be used in parallel to antiviral drugs.

Starting from December 2019, coronavirus disease 2019 (COVID-19) has emerged as a once-in-a-century pandemic with deadly consequences, which urgently calls for new treatments, cures and supporting apparatuses. Remdesivir was reported by World Health Organization (WHO) as the most promising drug currently available for the treatment of COVID-19. Here, we use molecular dynamics simulations and free energy perturbation methods to study the inhibition mechanism of remdesivir to its target SARS-CoV-2 virus RNA-dependent RNA polymerase (RdRp). In the absence of a crystal structure of the SARS-CoV-2 RdRp, we first construct the homology model of this polymerase based on a previously available structure of SARS-CoV NSP12 RdRp (with a sequence identify of 95.8%). We then build the putative binding mode by aligning the remdesivir + RdRp complex to the ATP bound poliovirus RdRp. The putative binding structure is further optimized with molecular dynamics simulations and demonstrated to be stable, indicating a reasonable binding mode for remdesivir. The relative binding free energy of remdesivir is calculated to be -8.28 ± 0.65 kcal/mol, much stronger than the natural substrate ATP (-4.14 ± 0.89 kcal/mol) which is needed for the polymerization. The ~800-fold improvement in the K_d from remdesivir over ATP indicates an effective replacement of APT in blocking of the RdRp binding pocket. Key residues D618, S549 and R555 are found to be the contributors to the binding affinity of remdesivir. These findings demonstrate that remdesivir can potentially act as a SARS-CoV-2 RNA-chain terminator, effectively stopping its RNA reproduction, with key residues also identified for future lead optimization and/or drug resistance studies.

Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, are responsible for approximately 2.65 million deaths per year. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: 1) Supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; 2) Supplementation above the RDA, but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and 3) Public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.

The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation and regulation such as the FDA and EMA are revising their emergency authorization use of several COVID-19 neutralizing antibodies. These MAbs proved to be unlikely effective against new variants especially Omicron descendants and several pharmaceutical companies are pursuing the development of more potent neutralizing antibodies. To address this issue, we used In Silico method we previously developed to assess 10 anti-SARS-CoV-2 antibodies propensity to neutralize the new Omicron’s subvariants EG.5, BA.2.86 and JN.1, based on comparative binding affinity of 3D generated models and previous experimental and clinical observations. Nine of these MAbs were once granted emergency use authorization, and one is currently under clinical investigation. The results showed that one antibody showed a marked increase of the binding energy for EG.5 compared to two antibodies that showed a significant increase with Pirola (BA.2.86) and JN.1. This data indicates that the new SARS-CoV-2 variant escapes neutralization of most of the available therapeutic NAbs. Furthermore, the data showed new potential therapeutic MAbs combination that could be effective for the treatment countermeasure of the new Omicron’s descendants or potential novel variants.

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) and Long COVID are characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and Long COVID, suggesting that use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation, as well as neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and Long COVID.

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

The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation and regula-tion such as the FDA and EMA are revising their emergency authorization use of several COVID-19 neutralizing antibodies. These NAbs proved to be unlikely effective against new variants espe-cially Omicron descendants and several pharmaceutical companies are pursuing the development of more potent neutralizing antibodies. To address the issue of using in silico prediction for the rapid assessment of anti-SARS-CoV-2 MAbs neutralization power, we used a computational method we developed previously, to evaluate 10 SARS-CoV-2 antibodies propensity to neutralize the new Omicron’s subvariants Eris (EG.5) and Pirola (BA.2.86) based on comparative binding affinity and previous experimental and clinical observations. Nine of these MAbs were once granted emergency use authorization, and one is currently under clinical investigation. The rapid, cost-effective in silico evaluation provided reliable predictions consistent with published clinical and experimental data. Furthermore, our data showed new potential therapeutic MAbs combi-nation that could be effective for the treatment countermeasure of the new Omicron’s subvariants Eris (EG.5) and Pirola (BA.2.86).

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against ancestral and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5 and XBB.1.5) in human serum. For ancestral strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity. The assay was robust against changes to virus/serum incubation time, cell seeding density, virus content per well, cell passage number, and serum interference. Analyte in serum samples was stable up to 5 freeze/thaw cycles and for up to 12 months of storage at –80 ± 10 °C. Similar results were observed for the variant-adapted MN50 assays. The conversion factor to convert assay result units to WHO international standard units (IU/mL) was determined to be 0.62 for the ancestral prototype strain. This MN50 assay will be useful for vaccine immunogenicity analyses in clinical trial samples, enabling assessment of vaccine immunogenicity for ancestral and variant strains as variant-adapted vaccines are developed.

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

This paper proposes a concise literature review aimed at identifying the current body of knowledge on the adoption of Social Networks in Crisis Management. The major input is a structured research question based on the initial reading around the topic. Before the recent pan-demic, most literature has focused on local crises, with a relatively low number of exceptions. Additionally, self-organizing system are spontaneous established between people who are af-fected by a crisis. Among the identified challenges, there is the need to integrate official commu-nication by emergency agencies with citizen-generated contents in a contest of credibility and trustworthiness. In certain cases, it has been reported a lack of specific competence, knowledge, and expertise, as well as a lack of sufficient policies and guidelines in the use of Social Networks. Those challenges need to be framed by considering the classic difficulties to provide timely and accurate information, to deal with fake news, unverified or misleading information, and infor-mation overload. Bridging major gaps though advanced analytics and AI-based technology is expected to provide a key contribution to establish and safely enable in practice an effective and efficient communication, to contrast dissonant mental models, which are often fostered by Social Networks, and to enable a shared situational awareness.

A machine learning method for classifying Lung UltraSound is here proposed to pro- vide a point of care tool for supporting a safe, fast and accurate diagnosis, that can also be useful during a pandemic like as SARS-CoV-2. Given the advantages (e.g. safety, rapidity, portability, cost-effectiveness) provided by the ultrasound technology over other methods (e.g. X-ray, computer tomography, magnetic resonance imaging), our method was validated on the largest LUS public dataset. Focusing on both accuracy and efficiency, our solution is based on an efficient adaptive ensembling of two EfficientNet-b0 models reaching 100% of accuracy, which, to our knowledge, outperforms the previous state-of-the-art. The complexity of this solution keeps the number of parameters in the same order as an EfficientNet-b0 by adopting specific design choices that are adaptive ensembling with a combination layer, ensembling performed on the deep features, minimal ensemble only two weak models. Moreover, a visual analysis of the saliency maps on sample images of all the classes of the dataset reveals where the focus is on an inaccurate weak model versus an accurate model.

The COVID-19 pandemic first observed in December 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has influenced every individual on the planet. The virus has influenced our lifestyle, education, economy and the environment. Though the vaccines against COVID-19 have provided protection against the disease; new strains of the virus have lowered the efficiency of the vaccines. There is still no effective therapy for the treatment of the disease. Understanding the protein structure of the virus may lead to the development of effective therapies for the disease. We recently mapped the structural proteins and non-structural proteins of SARS-CoV-2. The accessory proteins (Open reading frames, Orfs) of SARS-CoV-2 modulate the host environment to favor virus replication. This paper reports mapping the accessory proteins (Orfs) of SARS-CoV-2.

Background: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2. In Colombia, many commercial methods are now available to perform the RT-qPCR assays, and the laboratories must evaluate its diagnostic accuracy to ensure reliable results to suspected COVID-19 patients. The purpose of the study was to compare four commercial RT-qPCR assays for detection of SARS-CoV2 virus, from nasopharyngeal swab samples referred to Laboratorio Carvajal IPS, SAS of Tunja, Boyacá - Colombia. Methods: This prospective study was conducted on 152 samples of respiratory tract samples (Nasopharyngeal Swab) from patients with suspected SARS-CoV-2 infection. Diagnostic accuracy of GeneFinderTM COVID-19 Plus RealAmp (In Vitro diagnostic), One-Step Real-Time RT-PCR (Vitro Master diagnostica), Berlin modified protocol and gold standard Berlin protocol (Berlin Charite Probe One-Step RT-qPCR Kit, New England Biolabs) as reference was assessed. Operational characteristics were estimated in terms of sensitivity, specificity, agreement, and predictive values. Results: Using Berlin Charite Probe One-Step RT-qPCR Kit as reference, the sensitivity/specificity for the diagnostic tests were found to be GeneFinderTM COVID-19 Plus RealAmp Kit 100%/92.7%, One-Step Real-Time RT-PCR, One-Step Real-Time RT-PCR 92.75%/67.47%, and Berlin modified protocol 100%/96.39%. The results of four commercially available methods were found to be consistent with those obtained from Berlin Modified protocol analysis for % of the samples and showed good agreement (κ= 0.96). Concordant SARS-CoV2 negative and positive RT-qPCR results were reported for xxx and xxx samples, respectively. Summarize something about the Ct. Conclusion: Our data demonstrate that all commercially available methods are rapid and reliable for the identification of SARS-CoV-2 virus associated with COVID-19. One-Step RT-qPCR Kit and GeneFinderTM COVID-19 Plus RealAmp assay show optimal sensitivity compared with Belin modified protocol. In addition, there is no significant correlation between xxxxx

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

This paper presents the findings of an exploratory study on the continuously generating Big Data on Twitter related to the sharing of information, news, views, opinions, ideas, knowledge, feedback, and experiences about the COVID-19 pandemic, with a specific focus on the Omicron variant, which is the globally dominant variant of SARS-CoV-2 at this time. A total of 12028 tweets about the Omicron variant were studied, and the specific characteristics of tweets that were analyzed include - sentiment, language, source, type, and embedded URLs. The findings of this study are manifold. First, from sentiment analysis, it was observed that 50.5% of tweets had the ‘neutral’ emotion. The other emotions - ‘bad’, ‘good’, ‘terrible’, and ‘great’ were found in 15.6%, 14.0%, 12.5%, and 7.5% of the tweets, respectively. Second, the findings of language interpretation showed that 65.9% of the tweets were posted in English. It was followed by Spanish or Castillian, French, Italian, Japanese, and other languages, which were found in 10.5%, 5.1%, 3.3%, 2.5%, and <2% of the tweets, respectively. Third, the findings from source tracking showed that “Twitter for Android” was associated with 35.2% of tweets. It was followed by “Twitter Web App”, “Twitter for iPhone”, “Twitter for iPad”, “TweetDeck”, and all other sources that accounted for 29.2%, 25.8%, 3.8%, 1.6%, and <1% of the tweets, respectively. Fourth, studying the type of tweets revealed that retweets accounted for 60.8% of the tweets, it was followed by original tweets and replies that accounted for 19.8% and 19.4% of the tweets, respectively. Fifth, in terms of embedded URL analysis, the most common domains embedded in the tweets were found to be twitter.com, which was followed by biorxiv.org, nature.com, wapo.st, nzherald.co.nz, recvprofits.com, science.org, and other URLs. Finally, to support similar research and development in this field centered around the analysis of tweets, we have developed an open-access Twitter dataset that comprises tweets about the SARS-CoV-2 omicron variant since the first detected case of this variant on November 24, 2021.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiological agent of the current pandemic worldwide. The pathological condition induced by this pathogen is known as COVID-19 disease. SARS-CoV-2 associated pandemic has been defined as a “public health emergency of international concern” by the International Health Regulation Emergency Committee of the World Health Organization. To date, considerable efforts are in progress to develop more advanced strategies against SARS-CoV-2. Despite the numerous scientific studies published, our knowledge regarding this pathogen is still incomplete, as this virus has been identified only recently. Therefore, scientific investigation of the SARS-CoV-2 has been possible only for a short period of time and effective management of the serious forms of this disease is still lacking. Considerable efforts are in progress worldwide with the purpose to develop more advanced strategies against this pathogen. In this review, we have analyzed the structural and the biological SARS-CoV-2 characteristics and those of other well-known RNA viruses, with the aim to identify possible similarities and analogies between all these pathogens, may be a very useful approach. These infectious agents have been widely studied since several years ago and, a large series of scientific reports are available in the literature regarding this topic. Therefore, focusing on the Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Influenza viruses (IVs), we have collected their historical data, clinical manifestations, pathogenetic mechanisms and related infections. Taking advantage of the results of our research, we have assembled this narrative review, with the aim to get useful insights and lessons from HIV, HCV and IVs characteristics and, consequently, to transfer the obtained knowledge to the study of SARS-CoV-2 biology. There are well known differences between all these pathogens. In particular, they present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne pathogens, whereas HIV and HCV are bloodborne infectious agents. However, these viruses exhibit some potential common clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2. Accordingly, we have analysed and discussed the following points: 1) the biology, the pathogenesis and the clinical manifestations of SARS-CoV-2, HIV, HCV and IVs in mankind; 2) the onset and spreading of pandemics caused by respiratory viruses according to a perspective historical point of view; 3) the possible development of a persistent SARS-CoV-2 reservoir worldwide; 4) the possibility of SARS-CoV-2 reinfection/reactivation; 5) the possible involvement and impact of climatic factors in increasing the risk of SARS-CoV-2 spreading.

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

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

The novel coronavirus COVID- 19 disease is extremely contagious and has been spread worldwide. First COVID-19 case was identified in December, 2019 and within three months, more than one million affected cases and over 65,000 deaths have been reported. SARS-coronavirus 2 (SARS-CoV-2) also known as 2019-nCoV is a causative agent of COVID-19 disease and belongs to the SARS CoV (Severe Acute Respiratory Syndrome corona virus) family. The SARS-CoV-2 enters the human body by binding its viral surface spike protein with the host angiotensin-converting enzyme 2 (ACE2) receptors and cause infection. To prevent the virus entry and its transmission in the human body, we focused on the two domains of ACE2: i) the N-terminal extracellular binding domain (18-740 residues) reported for coronavirus spike interaction, and ii) the C-terminal cytoplasmic region (762-805 residues) to prevent the virus transmission. Therefore, we proposed: i) inhibition of receptor binding domain (RBD) of SARS-CoV-2 and human ACE2 protein may prevent the virus entry to the host and ii) inhibition of phosphorylation at Ser-787 of ACE2 protein may prevent the transmission of the virus in the COVID-19 patients. In the past, the critical role of Ser 787 in human ACE2 protein has been experimentally verified in SARS-CoV transmission, that upon binding to the receptor, SARS- CoV induces CKII- mediated phosphorylation of ACE2 at Ser-787 that in-turn facilitate virus entry to host cells, followed by replication and activation of ACE2, initiates downstream signaling leading to lung fibrosis. Therefore, in this study, we have suggested post-translational modification (PTM) O-β-GlcNAcylation, and two compounds Chloroquine and 2-hydroxybenzohydrazine might share the common pathways to prevent the COVID-19 infection in human. The addition of O-β-GlcNAcylation at same or neighboring Ser/ Thr residues results in phosphorylation inhibition and a change in protein structural and functional confirmations. Thereby, using neural networking methods, we have identified Ser/ Thr residues in ACE2 that are potential sites for phosphorylation and / or O-β-GlcNAcylation. Molecular docking showed that UDP-GlcNAc has more binding affinity with Ser-787 than the phosphoryl group. Moreover, chloroquine and 2-hydroxybenzohydrazine also showed great potential to bind at Ser-787 that may result in inhibition of Ser-787 phosphorylation and downstream signaling. Furthermore, O-β-GlcNAcylation, chloroquine and 2-hydroxybenzohydrazine showed their high affinity at ACE2-SARS-CoV-2receptor binding domain that may prevent the entry of SARS-CoV-2 into human body. In conclusion, inhibition of human ACE2 phosphorylation at Ser-787 and ACE2-SARS-CoV-2 binding domain could be promising targets against SARS-CoV-2 infection.

Understanding how the coronaviruses invade our body is an essential point, and the expression profile of coronaviruses receptor may help us to find where the coronavirus infects our body. We found that the coronavirus receptors, including angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-Cov-2, are digestion-related enzymes in human enterocytes. Coronaviruses are continually altering the binding receptor and binding modes during their evolution, but the potential target cell in the small intestine is constant when in the lung is inconstant. Enterocytes may act as a conserved cell reservoir for coronaviruses, which may be partially explained by the Red Queen hypothesis. We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies.

Long COVID is a persistent symptom that appears in many COVID-19 patients, regardless of whether they are asymptomatic, mild, or severe. At least 10% worldwide are suffering from long COVID. The anti-inflammatory effect was evaluated in LPS-treated RAW264.7 cells using six Korean national insurance-covered herbal prescriptions with therapeutic potential for mitigating inflammation in the respiratory tract, and additional network pharmacology analysis was performed. Soshihotang (SST) significantly downregulated iNOS and COX2 expression, reduced the production of NO (nitric oxide) and inflammatory cytokines, such as TNFα, IL-1β, and IL-6, and inhibited IκBα phosphorylation and reduced the nuclear translocation of NF-κB in LPS-treated RAW264.7 cells. Network pharmacological analysis showed that SST was closely related to the NF-κB signaling pathway. Further study on the potential of herbal prescriptions will be needed before they can be used clinically by long COVID patients.

Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

The SARS-CoV-2 Omicron variant and its sublineages continue to cause COVID-19—associated pediatric hospitalizations, severe disease, and death globally. BNT162b2 and CoronaVac are among the top most widely used COVID-19 vaccines. Much less is known on the Wuhan-Hu-1 strain based vaccines in the pediatric population compared to adults. Given the worldwide need for booster vaccinations to stimulate the immune response against new Omicron variants of SARS-CoV-2, we characterized the humoral and cellular immune response against Omicron variant BA.1 in a pediatric population aged 10 to 16 years who received heterologous vaccination based on two doses CoronaVac, two doses CoronaVac (2x) plus one booster doses BNT162b2 [CoronaVac(2x) + BNT162b2 (1x)], two doses CoronaVac plus two booster doses BNT162b2 [CoronaVac(2x) + BNT162b2 (2x)], and three doses BNT162b2. We observed that [CoronaVac(2x) + BNT162b2 (2x)] vaccination showed higher anti-S1 and neutralizing antibody titers and CD4 and CD8 T cell immunity specific to the Omicron variant compared to immunization with two doses CoronaVac alone. Furthermore, from all groups tested, immunity against Omicron was highest in individuals who received three doses BNT162b2. We conclude that booster vaccination with BNT162b2 promotes greater immunity against SARS-CoV-2 in the pediatric population compared to two doses CoronaVac alone.

The pathogenesis of coronavirus disease 2019 (COVID-19) is associated with a hyperinflammatory response. The mechanisms of SARS-CoV-2-induced inflammation are scantly known. Methylglyoxal (MG) is a glycolysis-derived by-product, endowed with a potent glycating action, leading to the formation of advanced glycation end products (AGEs), the major of which is MG-H1. MG-H1 exerts strong pro-inflammatory effects, frequently mediated by the receptor for AGEs (RAGE). Here, we investigated the involvement of MG-H1/RAGE axis as a potential novel mechanism in SARS-CoV-2-induced inflammation by resorting to human bronchial (BEAS-2B) and alveolar (A549) epithelial cells, expressing different levels of ACE2 receptor (R), exposed to SARS-CoV-2 spike protein 1 (S1). Interestingly, we found in BEAS-2B cells that do not express ACE2-R, that S1 exerted a pro-inflammatory action through a novel MG-H1/RAGE-based pathway. RAGE expression levels in nasopharyngeal swabs from SARS-Cov-2 positive and negative individuals, as well as glyoxalase 1 expression, the major scavenging enzyme of MG, seem to support the results obtained in vitro. Altogether, our findings reveal a novel mechanism involved in the inflammation triggered by S1, paving the way to the study of MG-H1/RAGE inflammatory axis in SARS-CoV-2 infection as a potential therapeutic target to mitigate COVID-19 associated pathogenic inflammation.

Balanced fear supports human rational decision making and useful behavioral responses. In contrast, overwhelming, persistent, and unbalanced fear can paralyze the individual and result in heightened anxiety, lack of cognitive flexibility, fear-based public compliance and serious mental health issues. Psychobiotics research has established that a healthy microbiome is required for balanced fear and mental health protection via control of fear extinction. The recent Covid-19 pandemic featured daily, persistent, fear-of-a single contagion conditioning on a global scale paired with various behavioral mandates (e.g., lockdowns of the healthy, masks, isolation from environmental microbes and each other) that degraded the human microbiome and isolated us from each other and useful environmental microbes. It also ignored the historic role of secondary bacterial pathobionts, in pandemic deaths. This narrative review examines how institutional promotion of fear-of-a single contagion, lack of balanced risk communication, and appalling disregard of our fundamental nature (as majority-microbial human superorganisms) resulted in problems rather than solutions. This review concludes that government-public health-media promotion of pervasive fear and microbiome-degrading behaviors: 1) increased public compliance, 2) reduced cognitive flexibility, and 3) increased risk of mental health conditions. It further argues that microbiome-first public health should be embraced to ensure that human freedom, rather than paralyzing fear, dominates our future.

Negative mental health in students currently is classified as a global crisis with the highest and lowest student achievers recognized at greatest risk. Public schooling, in reproducing accepted psychosocial beliefs through standardized learning, developed separately from necessitating student mental health, in contrast to self-directed learning. Differing from standardized learning, the objective of self-directed learning in public schools is the creation of relevant support structures for student mental health, promoting positive psychosocial outcomes. The designed separation of public schooling from both mental health and self-directed learning was first acknowledged—and lamented—by John Dewey, over 100 years ago, in anticipating today’s mental health crisis. Yet, in responding effectively to the limitations of COVID-19, self-directed learning became an acknowledged learning method in public schools, potentially able to be accommodated by them regularly in support of mental health through the use of online technology. This study investigates the COVID-19 results of self-directed online learning in public schools through a Google Scholar search of peer reviewed research regarding self-directed learning, online learning, and mental health during COVID-19, recommending support for self-initiated self-directed online learning so that self-directed learning can continue, post COVID-19, improving student mental health in public schools, leading to positive psychosocial outcomes.

Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread among the population. Aim: to study the evolution of SARS-CoV-2 humoral immunity in the Belarusian population relative to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing population immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health with the participation of the St. Petersburg Pasteur Institute (SPPI), taking into account WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by questionnaire using a cloud (internet server) service. To monitor population immunity, a cohort of 4,661 people (participating in all stages of seromonitoring) was formed from the overall volunteer group. Volunteers were randomized by age group (1-17, 18-29, 30-39, 40-49, 50-59, 60-69, 70+ years), region, and professional group. For the detection of antibodies (Abs) to nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), corresponding assay systems were used following manufacturer instructions. The study was conducted in 4 stages according to a single scheme. Results. In the 1st stage (pandemic month 15), collective immunity was due mainly to Nc+RBD+ Ab status alone. By the 2nd stage (carried out after 4 months), their share decreased 1.2-fold, while the share of volunteers who had only RBD Abs increased 1.7-fold. In the 3rd and 4th stages (carried out after 9 and 19 months), the share of persons with RBD+Nc‒ compared to the 2nd stage decreased by 3.5%; the proportion of persons with Nc+RBD‒ Abs increased by 1.5-fold. The most important factor in population immunity was vaccination of the population, the coverage of which reached 70% by the 4th stage. Among vaccines, the Sputnik V and Sputnik Light vector designs were used most often. The whole-virion, inactivated BIBP-CorV vaccine was used less often. Conclusion. The evolution of collective SARS-CoV-2 humoral immunity included a set of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence to nearly zero.

SARS-CoV-2 belongs to the group of RNA viruses with a pronounced tendency to mutate. Omicron BA.2.75 is a subvariant believed to be able to suppress the currently dominant BA.5. Omicron BA.2.75 is characterized by a greater infectivity compared to earlier Omicron variants. However, Gibbs energy of biosynthesis of virus particles is slightly less negative compared to those of other variants. Thus, the multiplication rate of Omicron BA.2.75 is lower than that of other variants. This leads to slower accumulation of newly formed virions and less damage to host cells, indicating evolution of SARS-CoV-2 towards decreasing pathogenicity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S), envelop (E), membrane (M), and nucleocapsid (N). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps (nsp3, nsp4, nsp6) and Orf3a are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

The use of the Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKIs are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib is the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in an early phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions associated with the treatment of CLL with BTK inhibitors, and examines its further implications.

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

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Since there is not a clear consensus about the possibility for COVID-19 to be an airborne disease, exists a controversy regarding the need to use surgical masks to prevent its spread. Here, using the Kepler conjecture for ideal packaging, the number of virions of different sizes that can be accommodated inside droplets was calculated and are proportional to the 3^rd potency of the droplet/virion diameter. The differences between particles of 5 um and 100 μm are around four orders of magnitude, explaining why the airborne spread is much more difficult but still possible. There is no solid evidence yet that the airborne coronaviruses may reach enough concentration to infect, but this may be the case under certain circumstances. The WHO partially recognizes now this fact in a warning to health workers (from my point of view too late, as it was the declaration of a pandemic). Another issue is whether the virus stays infective in aerosols generated from patients. This has not been directly proved yet except with artificial aerosols, but there are no reasons why the virus cannot remain in the air and be infective if the viral charge and time of exposure are enough. We must also consider whether the virus can infect the intestine; there are some signs in this sense. Finally, and most importantly, we need to reduce interactions by using surgical masks to flatten the curve, leave the quarantine and avoid a rebound. For cultural reasons, a social distance of 2 meters (2M) is extremely hard to manage. Surgical masks do reduce the interactions in conditions of proximity and, therefore, help to “flatten the curve”. The WHO and CDC “laissez-faire” on this matter do not help and we are running out of time. Anticipated actions, such as the use of surgical masks for the general population, are critical.

Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage of formation, these maladies can be effectively treated, leading to successful outcomes; curative therapies can halt illnesses from advancing, thus improving the quality of life, and long-term survival of the patient. Still cutting-edge upgrades in precision technologies are necessary for early, reliable, affordable, and rapid disease detection, but also are vital for the well-being of people and the future of global public health. The emerging role and utility of non-invasive and repeatable diagnostic test approaches for detection of health conditions has been liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator or signature (e.g., proteins), to provide valuable information on individual’s wellness and/or disease. Among the bodily secretions used for non-invasive diagnostics is sputum, a complex viscous gel-like biopolymeric network, that has gained growing recognition as a rich source of biomarkers of airway infections, pulmonary diseases, and serves as a determinant to reveal other illnesses. As per the World Health Organization, the burden of respiratory conditions is exacerbated by factors, ranging from considerable subjection to air pollution and occupational contaminants, to tobacco smoking and second-hand smoke, in addition to poor socio-economic status. Due to the likely increase of these determinants, respiratory tract ailments are on the rise, affecting the health of many individuals, in addition to putting stress on healthcare facilities and services worldwide. We therefore highlight the need to use expectorated or induced sputum specimens as a routine sample source for testing valuable protein biomarkers to diagnose these chronic maladies, to predict inflammation and disease progression, as well as monitor the effectiveness of treatments. Further, we discuss the urgency for fast and reliable point-of-care methods to detect and quantify crucial protein biomarkers in sputum specimens, and limitations faced when dealing with their complex matrices.

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance of inactivated SARS-COV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-COV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprising of UV-inactivated SARS CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (Limit of Detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a twenty amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates.

The Single Site Order – a policy restricting staff from working at multiple long-term care homes – was mandated by the Public Health Agency of Canada to control the spread of COVID-19 in long-term care homes, where nearly 70% of COVID-19-related deaths in Canada occurred. This mixed methods study assesses the impact of Single Site Order on long-term care residents in British Columbia. Interviews were conducted (residents (n=6), family members (n=9), staff (n=18), and leadership (n=10) from long-term care homes (n=4)) and analyzed using thematic analysis. Administrative data was collected between April 2019 – March 2020 and April 2020 – March 2021 and analyzed using descriptive statistics and data visualization. Qualitative and quantitative data were triangulated and demonstrate staffing challenges became worse during implementation of the SSO resulting in the mental and physical health deterioration of LTC residents. Qualitative data demonstrated decreased time for personalized and proactive care, increased communication challenges, and increased loneliness and isolation. Quantitative data showed a decline in activities of daily living, increased antipsychotic medication use, pressure ulcers, behavioural symptoms, and an increase in falls. Addressing staff workload and staffing shortages during SSO-related policy implementation is essential to avoid resident health deterioration.

Background: The exacerbation of psychosocial problems among children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic necessitates an assessment of the long-term mental health impact of pandemic interventions. Focusing on both pandemic-related factors and demographic variables, such as gender and daily habits, an analysis was conducted to under-stand how these elements continue to affect young populations in the post-pandemic era. Methods: In April 2023, a comprehensive online survey was administered to families in South Tyrol, Italy, with children aged 7–19 years, to ensure age and gender representation. The survey included par-ent ratings and adolescent (11–19 years) self-reports using standardized instruments to measure the symptoms of mental health problems (Strengths and Difficulties Questionnaire, SDQ), anxiety (Screen for Child Anxiety Related Emotional Disorders, SCARED), and depression (Patient Health Questionnaire-2, PHQ-2). Statistical analyses included descriptive statistics, chi-square tests, and unadjusted odds ratios (ORs). Results: Of the 4,525 valid responses, 1,831 were self-reported by adolescents. Notable gender differences in mental health outcomes were identified, along with significant demographic predictors, such as age, single parenthood, parental mental health problems, and immigrant background. Negative effects were associated with reduced family climate and increased screen time, whereas physical activity showed beneficial effects. Proxy reports overestimated adolescents' mental health problems, whereas self-report tended to underestimate them. Conclusions: Persistent mental health problems and gender disparities high-light the need for a public health approach. This should include accessible support services, resili-ence building, targeted support for vulnerable families and gender-specific interventions.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic in 2020, following which a global genetic vaccination program has been rapidly implemented as a fundamental solution. However, it has been reported worldwide that the modified mRNAs encoding spike proteins and lipid nanoparticles, which are used as drug delivery systems, not only cause thrombosis and cardiovascular disorders post vaccination, but might also cause diverse diseases involving all organs and systems, including the nervous system. Furthermore, the toxicity and pathogenicity of spike proteins may necessitate defining these proteins as nonbiological infective material. Based on these reports and the abundant evidence that has come to light in the past few years, this paper aims to draw the attention of medical professionals to the various risks associated with transfusion using blood products derived from long COVID patients or from genetic vaccine recipients, and to make proposals regarding specific inspection items, testing methods, regulations, etc. This paper provides insights to address the post-vaccination syndrome and its consequences following such genetic vaccination programs.