Background:Although highly strict social distancing and viral spread protection guidelines are in force, the reported numbers of COVID-19 cases across the world are still increasing. This indicates that we are still unable to completely understand the transmission routes of SARS-CoV-2. One of the possible routes that can play a significant role is the fecal-oral transmission since SARS-CoV-2 can replicate in the intestines as demonstrated by isolation of infectious virus from fecal samples of COVID-19 cases. Scope and approach:In this review, we compare the characteristics of SARS-CoV-2 with the distinctive characteristics of enteric foodborne viruses. We also discuss and respond to the arguments given in some reports that downplay the importance of foodborne transmission route of SARS-CoV-2. Key findings and conclusions:Enteric viruses such as human noroviruses (HuNoVs) and hepatitis A virus (HAV) are known to transmit through foods such as fresh produce and berries, leading to frequent multistate foodborne disease outbreaks all over the world. SARS-CoV-2 was found to share four distinctive characteristics of foodborne viruses that allow them to transmit through foods. This similarity in characteristics, recent report of detecting SARS-CoV-2 particles from frozen food packages in China, and recent suspected foodborne COVID-19 case in New Zealand, indicate that foodborne transmission of SARS-CoV-2 is more evident than previously thought possible. To support or deny this route of transmission, urgent research needs to be undertaken to answer two primary questions and many secondary ones as described in this review.

Reciprocal Personal/Public Protection (RPPP) featured with source control is introduced, Mask Discriminating Mouth and Nose (MDMN) is employed to serve the purpose, which includes polymer based mouth cover with optional nose cover. The new knowledge that mouth is a primary, active and dominant source of the virus has been well established, which is the base of MDMN. Source classification and related source control tools are discussed, mouth cover is recommended as the tool prioritized to use. Liquid droplets is identified as a hard issue related to mask, liquid droplets, mask fitting, comfort and facial recognition constitute real challenges of mask in addition to efficiency, All of these have been addressed with MDMN. Comparisons between MDMN and masks/face covering are taken on four aspects: efficiency and efficacy, tolerance and comfort, cost and waste, and civil rights and public interest. Mouth cover is recommended to replace the face covering and act as both a personal tool and a public utensil, mouth cover with nose cover can provide better protection than N95 etc. RPPP with MDMN, could be an alternative for lockdown, a parallel strategy to vaccine, and a collectively living way during the pandemic era. MDMN, featured with high efficiency protection, high degree comfort, easy wearing, tight-fitting, easy facial recognition & communication, reusability, cost-effective, environment friendly and scale manufacturing more readily and widely etc., is a simple and sustainable solution, which is essential for ordinary people to keep wearing it properly for protection.

In Kenya, millions of children have limited access to nurturing care. With the COVID-19 pandemic, it is anticipated that vulnerable children will bear the biggest brunt of the direct and indirect impacts of the pandemic. This review aimed to deepen understanding of the effects of COVID-19 on nurturing care from conception to four years of age, a period where the care of children is often delivered through caregivers or other informal platforms. The review has drawn upon the empirical evidence from previous pandemics and epidemics, and anecdotal and emerging evidence from the ongoing COVID-19 crisis. Multifactorial impacts fall into five key domains: direct health; health and nutrition systems, economic, social and child protection, and child development and early learning. The review proposes program and policy strategies to guide the re-orientation of nurturing care, prevent the detrimental effects associated with deteriorating nurturing care environments, and support the optimal development of the youngest and most vulnerable children. These include the provision of cash transfers and essential supplies for vulnerable households, and strengthening of community-based platforms for nurturing care. Further research on COVID-19 and the ability of children’s ecology to provide nurturing care is needed, as is further testing of new ideas.

To predict how the COVID-19 pandemic progresses, we developed a systematic method for predicting disease outcomes. In the method, we evaluate how personal disease outcomes are mainly affected by viral concentration and exposure time and four defense mechanisms: human innate immunity/host response, acquired immune response, inflammation resolution and micro circulation, and the available space in the thorax cage. By considering how pandemic measures affect viral exposure and those mechanisms, we found many pandemic measures are misused or abused to deliver long-term adverse impacts. We noted that lifestyles have been changed as a result of movement restriction measures. By using the method, we found that altered lifestyles are predicted to raise infection rate, disability and death risks in the future. We show that a person can use personal, environmental, emotional factors to reduce infection rate and death risk. To prove the validity of this finding, we extensively examined medical research models, holistic and reductionist models, epidemiological models, disease risk factors, etc, and found that population methods are unfit for studying holistic health, statistical population does not exist in most clinical trials, mathematical models were misused for studying disease properties for a population, mathematical equations for modeling personal diseases are beyond human ability to solve, statistical models are misused, population-derived treatments are inherently dangerous to patients, vaccines have limited benefits due to unique lung structure and rapid RNA mutation, and immune system damage is caused by fast viral replication rate. We found that altering biological properties to improve the defense mechanisms could prevent a super majority of deaths and prevent the virus from reaching a point to damage the immune system. For vulnerable persons, such measure is a viable strategy for surviving from the pandemic. As a whole, holistic personalized medicine is more powerful than population-based reductionist treatment by one to several orders of magnitudes. We urge people do their parts to force the medical establishment to abandon population treatment models that are responsible for failure of medicine and dissemination of misleading and factually wrong information on the effectiveness of medical treatments.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

The spread of the infection caused by the new coronavirus SARS-CoV-2 (COVID-19) became pandemic on March 11, 2020. From the time of the first cases (in November 2019, Wuhan, China), to date, a large number of COVID-19 observations have been accumulated in different age groups of patients both in China and abroad. Published scientific data allows us to conclude that children suffer from COVID-19 much less often than adults and tolerate the disease in a milder form, often appear to be asymptomatic. There is currently no final answer why children are less susceptible to this virus; however, scientists are increasingly inclined to consider a complex effect of the immune response and components of the renin-angiotensin system (RAS), which according to recent studies affects not only the cardiovascular system, but is also responsible for the activation of inflammatory reactions. A hypothesis of genetic predisposition to the development of severe forms of COVID-19 has recently been made. We conducted a search for publications in the databases and showed current scientific ideas about COVID-19 pathogenesis and factors influencing the disease development in childhood. Childhood immunity may have several protective features against SARS-CoV-2: immaturity of particular elements of the innate immune response, constitutional lymphocytosis with a shift towards anti-inflammatory Th2-response, as well as "trained" immunity. The influence of renin-angiotensin system reactions in this review is shown from two perspectives: expression of ACE2 receptors and polymorphisms of certain genes of this system. It was established that ACE2 transmembrane protein is not only the entry point for the virus but also plays a regulatory role, turning the pro-inflammatory vasoconstrictor angiotensin II into anti-inflammatory angiotensin (1-7), which has vasodilating properties. Higher ACE2 content in children compared with adults helps maintain balance in the renin-angiotensin system and prevents the development of complications. It was also shown that the presence of certain genetic polymorphisms (AGTR1, AGTR2, ACE2, ACE) could determine the imbalance inside the RAS, leading to more pronounced reactions of alveolocytes, vascular endothelium and smooth muscle fibers in response to SARS-CoV-2 infection due to a shift towards vasoconstrictor, proliferative and profibrotic mechanisms.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Introduction: In Part II of this three-part series, we expose techniques that can be used by the U.S. Centers for Disease Control and prevention (CDC) and Food and Drug Administration (FDA) to manipulate and throttle the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety monitoring system open to the public. The U.S. government’s recommendation of COVID-19 vaccines during pregnancy was more a product of propaganda than of science and plagued with conflicts of interest. The extreme breach of COVID-19 vaccine pregnancy complication safety signals documented in VAERS cannot be disregarded or concealed. As a result, CDC/FDA are moving to closed, government captured platforms, including V-safe, Vaccine Safety Datalink (VSD) system, and the Biologics Effectiveness and Safety (BEST) system. Public transparency of adverse events following COVID-19 vaccination in pregnancy should be increased, not thwarted. Methods: In Part I the CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024 for adverse events (AEs) involving pregnancy complications following vaccination. In Part II we investigate tactics discovered in VAERS that concealed vaccine injuries and deaths. Conflicts of interest, as well as specific communications and publications from the CDC/FDA and the New England Journal of Medicine (NEJM) are analyzed. Results: Of all VAERS AE reports, 8.47% (138,983) of COVID-19 reports had no vaccination date and thus were missing from the data presented in Part I of this series. We unconcealed data presented in Part I of this series to include VAERS case reports that were excluded when using standard queries because of an “unknown vaccination date”. The unconcealed data in the 37 AE cases reported in this study (Part II) ranged from 0 - 38% with a mean of 8.2% (standard deviation 9.7%) and the significant breaches of VAERS safety signals in Part I of this series were largely underestimated. Another method of concealing vaccine associated AEs is to exclude the specific vaccine type rendering it as an “unknown vaccine type”. “Unknown vaccine type” has logarithmically increased since the rollout of the COVID-19 vaccines in 2021, ranging from 1 to 400 cases between 1990 to 2018 to 11,461 cases in 2021. CDC/FDA granted $67 million via a Cooperative Agreement grant to Massachusetts Department of Public Health (MDPH) between July 1, 2019, to June 30, 2025. MDPH then made subawards under this grant to 21 influential public and private health and civic organizations, including NEJM’s owner, Massachusetts Medical Society (MMS). As one of the subawardees under the grant, MMS as owner of NEJM received over $426,000 in federal HHS/CDC grant money from 2019 to 2020 for “public health and medical emergency preparedness projects”. Conclusions: CDC/FDA has failed to capture and account for a significant number of AE case reports following COVID-19 in VAERS by a variety of techniques in an apparent attempt to sanitize the data. CDC’s Rochelle Walensky and NEJM’s Editor-in-Chief Eric Rubin pushed novel untested COVID-19 vaccines in pregnant women despite clear evidence from multiple sources that safety signals had been breached.

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

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

Global rapidly evolving events, e.g., COVID-19, are usually followed by countermeasures and policies. As a reaction, the public tends to express their emotions on social media platforms. Therefore, predicting emotional responses to events is critical to put a plan to avoid risky behaviors. This paper proposes a machine learning-based framework to detect public emotions based on social media posts in response to specific events. It presents a precise measurement of population-level emotions which can aid governance in monitoring public response and guide it to put in place strategies such as targeted monitoring of mental health, to react to a rise in negative emotions in response to lockdowns, or information campaigns, for instance in response to elevated rates of fear in response to vaccination programs. We evaluate our framework by extracting 15,455 tweets. We annotate and categorize the emotions into 11 categories based on Plutchik’s study of emotion and extract the features using a combination of Bag of Words and Term Frequency-Inverse Document Frequency. We filter 813 COVID-19 vaccine-related tweets and use them to demonstrate our framework’s effectiveness. Numerical evaluation of emotions prediction using Random Forest and Logistic Regression shows that our framework predicts emotions with an accuracy up to 95%.

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

Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declined within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants received ChAdOx1 and forty-two participants received BNT162b2 were enrolled into this study which evaluated the immune responses including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript) and five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization as well as 4 and 12 weeks after receiving the booster. This study showed a significantly higher B-cell response among the BNT162b2 than the ChAdOx1 booster group, particularly against the Omicron variant, as well as a trend of good T-cell immune response in the BNT162b2 group. Moreover, the immune response rapidly declined at 12 weeks after the booster. A fourth dose or a second booster should be recommended, especially for reducing Omicron severity.

Background: Acceleration of mass vaccination strategies is the only pathway to overcome the COVID-19 pandemic. Healthcare professionals and students have a key role in shaping public opinion about vaccines. This study aimed to evaluate the attitudes of dental students globally towards COVID-19 vaccines and explore the potential drivers for students' acceptance levels; Methods: A global cross-sectional study was carried out in February 2021 using an online ques-tionnaire. The study was liaised by the scientific committee of the International Association of Dental Students (IADS), and data was collected through the national and local coordinators of IADS member organizations. The dependent variable was the willingness to take the COVID-19 vaccine, and the independent variables included demographic characteristics, COVID-19-related experi-ence, and the drivers of COVID-19 vaccine-related attitude suggested by the WHO-SAGE; Results: A total of 6639 students from 22 countries representing all world regions responded to the ques-tionnaire properly. Their mean age was 22.06 ± 2.79 (17-40) years, and the majority were females (70.5%), in clinical years (66.8%), and from upper-middle-income economies (45.7%). In general, 22.5% of dental students worldwide were hesitant, and 13.9% rejected COVID-19 vaccines. The students in low- and lower-middle-income (LLMI) economies had significantly higher levels of vaccine hesitancy compared to their peers in upper-middle- and high-income (UMHI) economies (30.4% vs 19.8%; p < 0.001); Conclusions: The global acceptance level of dental students for COVID-19 vaccines was suboptimal, and their worrisome level of vaccine hesitancy was influenced by the socioeconomic context where the dental students live and study. The media and social media, public figures, insufficient knowledge about vaccines, and mistrust of governments and the pharmaceutical industry were barriers to vaccination. The findings of this study call for further implementation of epidemiology (infectious diseases) education within undergraduate dental curricula.

Background Hokkaido is the northernmost, least populous, and coldest of the Japanese islands. It was the first prefecture to be affected by COVID-19, while Kanagawa is home to one of the most populous areas of Japan, namely the Tokyo metro area. The Japanese government responded early during the pandemic by identifying infected patients, contact tracing, and performing PCR analysis on anyone who was suspected of having been exposed to SARS-CoV-2. The government has also been publishing information about each individual who tested positive for the virus. Both Hokkaido and Kanagawa started recording COVID-19 cases in the winter of 2020 and have detailed records of thousands of patients, thus providing an invaluable resource for the transmission and behavior of the virus. Methods The current study analyzed the COVID-19 registry data from the Hokkaido and Kanagawa prefectures. The Hokkaido registry contained 1,269 cases (674 (53%) females and 595 (47%) males) recorded between February 14 and July 22, 2020. The Kanagawa registry had 3,123 cases (1,346 (43%) females and 1,777 (57%) males. The final data contained a total of 4,392 cases (2,020 (46%) females and 2,372 (54%) males). By leveraging the information on viral transmission paths available in the registry data, we performed exponential random graph model (ERGM) network analysis to examine demographic and symptomological homophilies of the SARS-CoV-2 viral transmission networks. Results We observed age, symptomatic, and asymptomatic homophilies in both prefectures. Furthermore, those patients who contracted the virus through secondary or tertiary contacts were more likely to be asymptomatic than those who contracted it from primary infection cases. The transmission networks showed that transmission occurred significantly in healthcare settings, as well as in families, although the size of the networks was small in the latter. Most of the transmissions stopped at the primary and secondary levels and no transmission beyond quaternary was observed. We also observed a higher level of asymptomatic transmission in Kanagawa than in Hokkaido. Conclusions Symptom homophilies are an important component of COVID-19 and suggest that nuanced genetic differences in the virus may affect its epithelial cell type range and can thus result in the diversity of symptoms seen in individuals infected by SARS-CoV-2. Moreover, environmental variables such as temperature and humidity may also be playing an important role in the overall pathogenesis of the virus.

The COVID-19 pandemic has resulted in a wide range of spatial interventions to slow down the spread of the virus. The spatial limitations of narrow public circulation spaces within informal settlements, which house over one billion people around the world, make it impossible for pedestrians to practice physical distancing (or social distancing). In this paper, we propose a flexible mathematical method, named the Cluster Lane Method, for turning a planar circulation network of any size or complexity into a network of unidirectional lanes, making physical distancing possible in narrow circulation spaces by limiting face-to-face interactions. New notions and theorems about oriented graphs in graph theory are introduced. The paper ends with a discussion of the potential implementation of this cost-efficient, low-tech, sustainable solution, and with the introduction of a novel unidirectional tactile paving for the visually impaired.

Thermal sterilization is generally avoided for 3-D printed components because of the relatively low deformation temperatures for common thermoplastics used for material extrusion-based additive manufacturing. 3-D printing materials required for high-temperature heat sterilizable components for COVID-19 and other applications demands 3-D printers with heated beds, hot ends that can reach higher temperatures than polytetrafluoroethylene (PTFE) hot ends and heated chambers to avoid part warping and delamination. There are several high temperature printers on the market, but their high costs make them inaccessible for full home-based distributed manufacturing required during pandemic lockdowns. To allow for all these requirements to be met for under $1,000, the Cerberus – an open source three-headed self-replicating rapid prototyper (RepRap) was designed and tested with the following capabilities: i) 200^oC-capable heated bed, ii) 500^oC-capabel hot end, iii) isolated heated chamber with 1kW space heater core and iv) mains voltage chamber and bed heating for rapid start. The Cereberus successfully prints polyetherketoneketone (PEKK) and polyetherimide (PEI, ULTEM) with tensile strengths of 77.5 and 80.5 MPa, respectively. As a case study, open source face masks were 3-D printed in PEKK and shown not to warp upon widely home-accessible oven-based sterilization.

The relentless challenges posed by the COVID-19 pandemic have placed immense pressure on densely populated regions, such as Hong Kong, particularly in the context of an aging population. The burgeoning demand for healthcare services has necessitated the optimization of resource al-location within healthcare systems. This research presents an innovative analytical queueing model specifically tailored to address the intricate gridlock dynamics prevalent in healthcare systems, with a focused application in the challenging landscape of COVID-19 management. Hong Kong, like numerous other regions, has experienced a demo-graphic transition leading to heightened healthcare demands. Traditional methodologies for scrutinizing gridlock issues in healthcare settings, including simulation models, often prove suboptimal within the context of sophisticated optimization frameworks. This study, however, delves into analytical queueing models, offering a more efficient and effective approach. These models have been underexplored, primarily due to the intricacies involved in modeling gridlock propagation within restricted capacity, a critical concern magnified by the COVID-19 pandemic. The novel Queueing Model introduced in this research incorporates the maintenance of queue capacities and topological aspects as exogenous parameters, rendering it exceptionally adaptable for diverse gridlock-related applications. This adaptability is especially pertinent to healthcare management during the COVID-19 crisis. The model meticulously integrates the concept of gridlock, furnishing a comprehensive comprehension of its origins and repercussions. Validation of this model involves rigorous comparison with established methodologies, exact results, and simulation data, consistently high-lighting its versatility and precision. By applying the model to healthcare management, we scrutinize the dynamics of patient flow within a Hong Kong hospital, placing specific emphasis on the critical issue of bed blockage, further exacerbated by the COVID-19 pandemic. The model's gridlock decomposition unearths the nuanced impact of bed blockage on distinct hospital units, addressing the imperative requirement for quantifying in-patient bed blockage within healthcare systems during a pandemic.

The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.

Home confinement during the COVID-19 pandemic has been accompanied by dramatic changes in household food dynamics that can significantly influence health. This systematic literature review presents parental perspectives of the impact of COVID-19 lockdown on food preparation and meal routines, as well as other food-related behaviors, capturing both favorable and unfavorable changes in the family food environment (FFE). Themes and trends are identified and associations with other lifestyle factors are assessed. In overall, families enjoyed more time together around food, including planning meals, cooking, and eating together. Eating more diverse foods and balanced meals was combined with overeating and increased snacking, as parents became more permissive towards food; however, food insecurity increased among families with the lowest income. Adoption of meal planning skills and online shopping behavior emerged alongside behaviors aimed at self-sufficiency, such as bulk purchasing and stockpiling. These results are an important first step in recognizing how this pandemic may be affecting the FFE, including low-income families. Future obesity prevention and treatment initiatives, but also ongoing efforts to address food management, parental feeding practices, and food insecurity, can account for these changes moving forward.

Identifying anti-spike antibodies that exhibit strong neutralizing activity against current dominant circulating variants and antibodies that are escaped by these variants have important implications in the development of therapeutic and diagnostic solutions as well as in improving understanding of the humoral response to SARS-CoV-2 infection. We characterized seven anti-RBD monoclonal antibodies for their binding activity, pairing capability and neutralization activity to SARS-CoV-2 and three variant RBDs (UK, SA and BR P.1) via lateral flow immunoassays. The results allowed us to group these antibodies into three distinct epitope bins. Our studies showed that two antibodies had broadly potent neutralizing activity against SARS-CoV-2 and these variant RBDs and that one antibody did not neutralize the SA and BR P.1 RBDs. The antibody escaped by the SA and BR P.1 RBDs retained binding activity to SA and BR P.1 RBDs but was unable to induce neutralization. Further, we demonstrated that the lateral flow immunoassay can be a rapid and effective tool for antibody characterization, including epitope classification and antibody neutralization kinetics. From these studies, the potential contributions of the mutations (N501Y, E484K and K417N/T) contained in these variants’ RBDs on antibody pairing capability, neutralization activity and therapeutic antibody targeting strategy are discussed.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

We present a new mathematical model of disease spread reflecting specialties of covid-19 epidemic by elevating the role social clustering of population. The model can be used to explain slower approaching herd immunity in Sweden, than it was predicted by a variety of other mathematical models; see graphs Fig. \ref{GROWTH2}. The hierarchic structure of social clusters is mathematically modeled with ultrametric spaces having treelike geometry. To simplify mathematics, we consider homogeneous trees with $p$-branches leaving each vertex. Such trees are endowed with algebraic structure, the $p$-adic number fields. We apply theory of the $p$-adic diffusion equation to describe coronavirus' spread in hierarchically clustered population. This equation has applications to statistical physics and microbiology for modeling {\it dynamics on energy landscapes.} To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider {\it linearly increasing barriers.} This structure matches with mild regulations in Sweden. The virus spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This behavior matches with the covid-19 epidemic, with its cluster spreading structure. Our model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. We present socio-medical specialties of the covid-19 epidemic supporting our purely diffusional model.

The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines which are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

While the history of Lough Derg is extremely well-documented, there have been com-paratively fewer ethnographic reports. Given the highly elaborate Lough Derg websites and multiple postings by Lough Derg pilgrims, this researcher anticipated that Lough Derg – like many other Irish pilgrimages - would attract mostly recreational tourists. It does not. Pilgrims to Lough Derg do not see the site as primarily a tourist destination. Instead, they see Lough Derg primarily as a locus of intense religious experience. Lough Derg 3-day pilgrimages are rigorous and entail considerable self-sacrifice: fasting, sleep deprivation, cold, bare feet, prayer, no cell phones, and exposure to jagged rocks. Lough Derg’s 3-day pilgrimages closely follow patterns established centuries ago. Lough Derg is both "modern" and "timeless." It selectively incorporates ancient ritual and 21st century technology. This paper looks at the impact of the covid19 epidemic on Lough Derg pilgrimages. The site was closed to pilgrims during the 2020-2021 season and an on-line virtual pilgrimage was offered as a substitute. One unintended consequence of this virtual pilgrimage is that many pilgrims to Lough Derg now give greater prominence to what Corin Braga has categorized as fisi (ecstatic revelations) than to the physical journey itself (i e. somanodias). Post-covid pilgrims highlight the Internet: production of virtual texts and Internet vlogs. As in most pilgrimages worldwide, contemporary pilgrims to Lough Derg arrive with varied expec-tations and myriad motives. This ethnographic report examines these motives and offers a critique of James L. Smith (2016), who, like Edith and Victor Turner (1978) before him – saw Lough Derg as a symbol of Irish nationalism. Smith highlighted Lough Derg’s “moral geography” which, he argued, stems from its long history of isolation. But Post- covid Lough Derg is no longer isolated. The site has become more accessible through organized bus tours, improved public transportation, and development of a commercial tourist infrastructure.

The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones etc. and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases etc. and the list is increasing gradually. In this review, we summarize NETs mediated pathophysiology of different diseases, focus on some updated potential therapeutic approaches against NETs and share our future perspectives.

(1) Background: The COVID-19 pandemic had a devastating impact on the world, causing widespread illness and death. It is essential to focus on prevention strategies to limit the spread of the disease. Despite the advent of vaccines, maintaining a vigilant approach to prevention remains paramount. While vaccines are essential, they do not guarantee absolute immunity, and their protective effect may diminish over time; (2) Methods: We reviewed effective strategies to prevent COVID-19 transmission. We focused on me-ta-analyses (MA), literature reviews (LR) and the health care context. Various prevention measures and interventions were reviewed. Both es-tablished practices and unresolved issues were considered; (3) Results: Standard precautions (SP) as the cornerstone of infection control, with hand hygiene and mask use as key components. Debate about the relative importance of droplet versus aerosol transmission led to differences in recommendations between agencies at the onset of the pandemic. We have clarified the role of personal protective equipment (PPE), including eye protection. The effectiveness of masks in pre-venting transmission is reviewed. The use of surgical masks is recommended to prevent droplet transmission, while eye protection is recommended in combination with masks. Although data show some risk reduction, the clear superiority of N95/FFP2 over surgical masks remains unproven. In terms of room occupancy, ventilation is critical in reducing the risk of transmission in poorly ventilated environments. The use of negative pressure isolation rooms (NPIRs) is being investigated. The presence of viral RNA on surfaces does not necessarily indicate infectivity, and the risk of transmission by surface contact is low if surfaces are properly maintained and hand hygiene is practised regularly. Testing for SARS-CoV-2 in asymptomatic persons in healthcare settings may help prevent transmission; (4) Conclusions: Prevention of SARS-CoV-2 transmission requires a multifaceted approach, including reducing particle emissions from infected persons by wearing masks, eliminating aerosols by ventilation, ensuring physical separation, and protecting exposed persons with masks and eye protection.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.

The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

One of the main problems for managing global crises is to clarify and reduces drivers of systemic weaknesses to face complex emergencies. This study here analyzes the relation between public debt, healthcare expenditures and fatality rates in the presence of pandemic crises, such as COVID-19. Statistical evidence, based on a sample of European countries, here shows that high public debt over time reduces health expenditures and increases the vulnerability of countries to face emergencies, such as COVID-19 pandemic crisis. Regression analysis with a log-log model suggests that when European countries experience a 1% increase in healthcare expenditure per capita, in general they have a 1.2% reduction in the COVID-19 fatality rate. Main implications of this study to reduce the systemic risk and vulnerability to environmental threats are that countries must reduce public debt with good governance and institutions without reducing the allocation of economic resources to the healthcare sector in order to improve the preparedness to unforeseen emergencies and crises, such as pandemics, natural disasters, conflicts, and other environmental threats.

Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.

The prevalence of internet gaming disorders (IGD) is considerably high among youth, especially with social isolation imposed by the ongoing COVID-19 pandemic. IGD adversely affects mental health, quality of life, and academic performance. The Internet Gaming Disorder Scale (IGDS9-SF) is designed to detect IGD according to DSM-IV diagnostic criteria. However, inconsistent results are reported on its capacity to diagnose IGD evenly across different cultures. To ensure the suitability of the IGDS9-SF as a global measure of IGD, this study examined the psychometric properties of the IGDS9-SF in a sample of Sri Lankan university students (N = 322, mean age =17.2 ± 0.6, range = 16-18 years, 56.5% males) and evaluated its measurement invariance across samples from Sri Lanka, Turkey, Australia, and the USA. Among Sri Lankan students, a unidimensional structure expressed good fit, invariance across different groups (e.g., gender, ethnicity, and income), adequate criterion validity (strong correlation with motives of internet gaming, daily gaming duration, and sleep quality), and good reliability (alpha = 0.81). Males and online multiplayers expressed higher IGD levels, greater time spent gaming, and more endorsement of gaming motives (e.g., Social and Coping) than females and offline players. Across countries, the IGDS9-SF was invariant at the configural, metric, and scalar levels, albeit strict invariance was not maintained. The lowest and highest IGD levels were reported among Turkish and American respondents, respectively. In conclusion, the IGDS9-SF can be reliably used to measure IGD among Sri Lankan youth. Because the scale holds scalar invariance across countries, its scores can be used to compare IGD levels in the studied countries.

On February 24, 2022 Russia started the full-scale invasion of Ukraine, which created an unprecedented number of refugees. To estimate the influence of this humanitarian disaster on the COVID-19 pandemic dynamics, the averaged daily numbers of cases and reproduction numbers in Ukraine, the UK, Poland, Germany, the Republic of Moldova, and in the whole world were calculated for the period February-April 2022. The registered numbers of cases were compared with ones calculated with the use of the generalized SIR-model and corresponding parameter identification procedure for the previous epidemic waves in Ukraine, Poland, Germany, and the world. Since before February 24, 2022 the estimation of the number of infectious persons per capita in Ukraine 3.6 times exceeded the global figure, the increase of the number the new cases and the pandemic duration was expected. In March 2022 the increase of the averaged number of new cases in the UK, Germany, and worldwide was visible. A simple formula to estimate the effective reproduction number based on the smoothed accumulated numbers of cases is proposed. The results of calculations agree with the figures presented by John Hopkins University and demonstrate a short-term growth of the reproduction number in the UK, Poland, Germany, Moldova, and worldwide in March 2022.

Like all RNA viruses, SARS-CoV-2 shows high mutation rate, which has led to the emergence of new variants. Among them, Gamma and Delta developed at the turn of 2020-2021 in Amazonas and India, two ecoregions characterized by hot-humid weather, very similar to that of the summer season due to climate change in Italy, the first Western country to have been hit hard by COVID-19 and to experience lockdown restrictions in a democratic framework of 58,85 million people. Methods: during the state of national health emergency and the Draghi government, the Civil Defense Department daily released the aggregate data coming from the Ministry of Health, the Higher Institute of Health, the Independent Provinces and the Italian Regions, in order to inform about the pandemic situation in Italy. Among these data there were the number of deaths, hospitalizations in intensive care units (ICU), non-ICU patients, contagions, and performed swabs. By means of a team effort, we have collected and elaborated all these data, comparing COVID-19 pandemic in Italy during the summers 2020 (following the nationwide lockdown), 2021 and 2022. Results: from summer 2020 (before mass vaccination) to summers 2021 (after primary mass vaccination) and 2022 (after booster mass vaccination) all pandemic trend indicators have showed a sharp worsening in Italy. COVID-19 deaths increased by ≈298% and ≈834%, ICU hospitalizations by ≈386% and ≈310%, non-ICU hospitalizations by ≈224% and ≈600%, contagions by ≈627% and ≈6.850% (i.e. ≈68,50 times), swabs by ≈354% and ≈370%, and the mean positivity rate passed from ≈1% to ≈2% and ≈20%, respectively. Conclusions: SARS-CoV-2 can be transmitted in any climate, including areas with hot and humid weather, and the emergence of variants adapted to hot-humid climate may result in summer COVID-19 outbreaks, even in neither tropical nor subtropical countries. Although COVID-19 vaccines can confer cross-protection against newly emerging variants, this cross-immunity is obviously not absolute but limited, also taking into account that vaccine protection wanes considerably after 6 months. It follows that a subject vaccinated at the beginning of winter will not be completely covered in the height of summer, without forgetting the unvaccinated. As a final remark, the long nationwide lockdown made it possible to flatten SARS-CoV-2 circulation and, therefore, its negative impact on Italy during summer 2020.

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

The COVID-19 pandemic drew public attention back to the living conditions related to housing, access to green areas in close neighbourhood and nearby recreation. Several studies confirm that visiting green spaces improved the health and wellbeing in times of crisis. This representative study for the metropolitan area of Vienna, Austria’s capital, confirms the high relevance of contact with nature, particularly for citizens to cope with the negative consequences and perceived stress, anxiety, nervousness and many other negative symptoms experienced during the health crisis. It highlights the importance of nearby smaller but also medium to large scale green areas in cities for health and wellbeing of the population. Moreover, it specifically adds novel insights on age effects in use and perception of urban green spaces during COVID-19 pandemic. The online panel survey (n=1012) was conducted in summer 2021. In order to obtain a representative sample reflective of the population’s characteristics, a (stratified) random sample was selected by applying the quota method. The objective was to obtain a sample which represented gender, age and regional distribution of the population of the City of Vienna as well as the immediately surrounding local communities. Interestingly, particularly young people spent more time outside in green areas during the pandemic, discovered novel spaces for the first time and stated a high relevance of contact with nature for their wellbeing. Elderly people above sixty five, on the contrary, stayed more frequently at home. Significant differences are visible between the age groups also with regard to negative symptoms experienced in case of restricted access to green areas due to strict pandemic measures such as lockdowns and quarantine. All age groups, however, similarly acknowledged the importance of green areas for their physical, mental and emotional health in general during the pandemic.

INTRODUCTION: The purpose of the study was to determine (a) the overall preclinical character; (b) the cumulative cutoff values and the risk ratio, and (c) the factors associated with severity by a unidimensional and multidimensional analysis on 2173 Sars-Cov2 patients. METHODS: The machine learning study population consisted of 2173 patients (1587 mild and non symptoms patients, 377 moderate patients, 209 severe patients). The status of the patients was recorded from September 2021 to March 2022. RESULTS: The Covid19 Severity directly links with a significant correlation to Age, Score index of the chest X-ray, percentage and quantity of neutrophils, Albumin, C reactive protein, and ratio of Lymphocytes. Their important cut off values (from regression analysis) respectively are: 77.56 years old (the mild-moderate group), 5.53 (the mild-moderate group) and 10.51 (the moderate-severe group), 84.80% (the mild-moderate group) and 87.74%(the moderate-severe group), 11.77G/L (the moderate-severe group), 29.73g/L (the moderate-severe group), 7.46mg/dL (the mild-moderate group), 6.32% (the moderate-severe group). Their significant (p<0.0001) R score correlation with the severity of Covid19, are: 0.44, 0.52 and 0.52, 0.33 and 0.44, 0.42, -0.43, 0.40, -0.41. Their significant risk ratio (p<0.00001) from the meta-analysis, respectively are: 4.19 [3.58-4.95], 3.29 [2.76-3.92] and 3.03 [2.4023;3.8314], 3.18 [2.73-3.70] and 3.32 [2.6480;4.1529], 3.15 [2.6153;3.8025], 3.4[2.91-3.97], 0.46 [0.3650;0.5752] (p<0.00001), 0.34 [0.2743;0.4210]. The pair ALT – Leucocytes and Transferrin – Anion Chloride get the most important correlation shift. ALT – Leucocytes show the important negative link (R=-1, p<0.00001) in the mild group to the significant positive correlation in the moderate group (R=1, p<0.00001). Transferrin–anion Chloride has an important positive association (R=1, p<0.00001) in the mild group with a significant negative correlation in the moderate group (R=-0.59, p<0.00001). The network map and HCA show that in the mild-moderate group, the closest neighbors with the Covid19 severity are ferritins, Age. Then there is C-reactive protein, SI of X-ray, Albumin, and Lactate dehydrogenase, which are the next close neighbors of these three factors. In the moderate-severe group, the closest neighbors with the Covid19 severity are Ferritin, Fibrinogen, Albumin, the quantity of Lymphocytes, SI of X-ray, white blood cells count, Lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: Complete multidimensional study in 2173 Covid19 patients in Vietnam shows the whole picture of all the preclinical factors, which may become the clinical reference marker for surveillance and diagnostic management

Measures in the SARS-CoV-2 pandemic were based on rough ideas regarding transmission routes of pathogens. Quantified models of physical transmission routes are mostly lacking, a gap to be filled. Vaccines and medicines, important, are not studied here. We first survey main routes, from primary production in the alveoli and intestines to emissions, environmental routes, to exposure and alveolar infection. Next, specific routes are modelled, mostly at a preliminary state, open to systematic improvement. Starting from a standardized emitter, modelling results show extreme differences in potential exposure, in a range covering up to 4 orders of magnitude. The outcomes are pathogen-specific, already different between SARS-CoV-2 and influenza. Extreme exposures may result in smaller spaces; with lower ventilation rates; with a high density of emitting persons per m3; who stay there for several hours; and visitors staying more than a few minutes. In spaces where a build-up of concentrations is low, exposures are low, lowest in open air situations. A main conclusion for the next pandemic is that a quantified model can give strong guidance on where measures are primarily due. For SARS-CoV-2, ventilation can be improved short-term. Longer-term, effective ventilation rules and adaptation of buildings may reduce high exposures substantially.

Abstract: A prevalence boundary (PB) marks the point in prevalence where the false omission rate, RFO=FN/(TN+FN), exceeds the tolerance limit for missed diagnoses. Objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise: Tier-1) 90%, 95%; Tier-2) 95%, 97.5%; and Tier-3) 100%, ≥99%, respectively. Repeating a T2 test improves the PB from 44.6% to 95.2% (RFO 5%). In the FDA-university-commercial evaluation, RAgTs generated sensitivity of 34.4%, which improved to 55.3% when repeated, then 68.5% with the third test. With RFO=5%, PBs were 7.37/10.46/14.22%, respectively. PB analysis suggests RAgTs should achieve clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.

Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.

Advances in biological sciences have been applied in medicine, agriculture and industry with great benefit. Some recent trends in society, governance structures and communications, however, appear to be hampering the use of new scientific findings for controlling infectious diseases. These limitations are illustrated with examples related to (i) the adaptation of fresh water mosquito vectors of major arboviral diseases to salinity in coastal areas with consequences for disease transmission, (ii) understanding the implications of reduced dengue transmission during the COVID-19 lockdown for dengue control, (iii) causes underlying the rapid spread of the malaria vector Anopheles stephensi in South Asia and Africa, (iv) the application of serodiagnostic techniques for Lyme disease and tick-borne relapsing fever caused by tick-borne bacteria of the genus Borrelia, and (v) COVID-19 prevention.

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNFα suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNFα, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

Coronavirus Disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm,” and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson's disease (PD), which is characterized by the formation of Lewy Bodies made of α-Synuclein protein encoded by synuclein alpha (SNCA). This study presents the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis, the study identifies the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream Effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

Despite extensive investigations of the Depression Anxiety Stress Scales-21 (DASS-21) since its development in 1995, its factor structure and other psychometric properties still need to be firmly established, with several calls for revising its item structure. Employing confirmatory factor analysis (CFA), this study examined the factor structure of the DASS-21 and five shortened versions of the DASS-21 among psychiatric patients (N = 168) and the general public (N = 992) during the COVID-19 confinement period in Saudi Arabia. Multigroup CFA, Mann Whitney W test, Spearman’s correlation, and coefficient alpha were used to examine the shortened versions of the DASS-21 (DASS-13, DASS-12, DASS-9 (two versions), and DASS-8) for invariance across age and gender groups, discriminant validity, predictive validity, item coverage, and internal consistency, respectively. Compared with the DASS-21, all three-factor structures of the shortened versions expressed good fit, with the DASS-8 demonstrating the best fit and highest item loadings on the corresponding factors in both samples (χ2(16, 15) = 16.5, 67.0; p = 0.420, 0.000; CFI= 1.000, 0.998; TLI = 0.999, 0.997; RMSEA = 0.013, 0.059, SRMR = 0.0186, 0.0203). It expressed configural, metric, and scalar invariance across age and gender groups. Its internal consistency was comparable to other versions (α = 0.94). Strong positive correlations of the DASS-8 and its subscales with the DASS-21 and its subscales (r = 0.97 to 0.81) suggest adequate item coverage and good predictive validity of this version. The DASS-8 and its subscales distinguished the clinical sample from the general public at the same level of significance expressed by the DASS-21 and other shortened versions, supporting its discriminant validity. Neither the DASS-21 nor the shortened versions distinguished patients diagnosed with depression and anxiety from other conditions. The DASS-8 represents a valid short version of the DASS-21, which may be useful in research and clinical practice for quick identification of individuals with potential psychopathologies. Diagnosing depression/anxiety disorders may be further confirmed in a next step by clinician-facilitated examinations. Brevity of the DASS-21 would save time and effort used for filling the questionnaire and support comprehensive assessments by allowing the inclusion of more measures on test batteries.

Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.