Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

Earnings management and financial distress are two critical facets of financial management in corporations that have lately been the focus of thorough research from both scholars and practitioners. The purpose of the research is to evaluate the influence of financial distress on the earnings management of companies listed at the NSE during the pre- and post-COVID eras. Multiple linear regression was applied in this study to examine the causal association between earnings management and financial distress. To assess the effect of financial distress on earnings management, the study analyzed data from 37 listed companies during the pre-COVID and post-COVID periods. The methodology also takes into account control factors like firm size, GDP, and inflation. The pre-COVID research indicates a significant positive correlation between financial strain and earnings management. In contrast, the correlation between financial distress and earnings management is not statistically significant in the post-COVID analysis. However, research shows that firm size has a statistically significant negative influence on managing earnings. The results of this study show that smaller firms are more inclined to engage in earnings management during the post-COVID era than bigger ones.

In Los Angeles, at one point, the Covid-19 testing positivity rate was 6.25%, or one in sixteen. This translates to, on average, one in sixteen specimens testing positive and the vast majority testing negative. Usually, we run sixteen tests on sixteen specimens to identify the positive one(s). This process can be time consuming and expensive. Since a group of negative specimens pooled together for testing will produce a negative result, one single test could potentially eliminate many specimens. Only when the pooled specimen tests positive do we need further testing to identify the positive one(s). Based on this concept, we designed a strategy that will identify the positive specimen(s) efficiently. Assuming one in sixteen specimens is positive, we find that only four tests are needed. Furthermore, we can run them simultaneously, saving both resources and time. Although, in the real world, we cannot make the assumption of only one positive specimen, the same strategy works with slight modification and proves to be much more efficient than the conventional testing. Our strategy returns an answer 48% of the time in four tests and one time cycle. Overall, the average number of tests is seven or eight depending on the follow-up testing, and the average time cycle is about one and a half.

Introduction: Due to COVID-19 pandemic, performance of many program has been declined and Tuberculosis (TB) program is not an exception. TB case detection and notification has been recognized as one of worst hit area. The objective of this study was to explore the TB notification status of India during this pandemic and explore options to mitigate the issue. Methods: A secondary data analysis was performed on open source TB notification database of India. Relevant literature review was done to find out remedies based on the different initiative taken by different states of India. Results: In 2020, total TB notification decreased in all the states in comparison to 2019. The percentage of loss in the country was 34%. Private TB notification also decreased in 2020 in all the states except in Jharkhand. The percentage of loss in private TB notification in the country was 35%. Notification started declining in the month of February 2020 and it was lowest in the month of April-2020. The trend of notification began to improve since May 2020 when the States started taking innovative initiatives like Integrated TB Covid Case Search. Conclusion: Due to the ongoing COVID-19 pandemic the notifications of TB cases declined noticeably which has a serious implication in terms of silent spread within household and community. But the picture can be improved with integrated approach for TB-COVID case finding and management.

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.

Understanding the motivations and decisions behind COVID-19 vaccine acceptance is crucial for designing targeted public health interventions to address vaccine hesitancy. We conducted a qualitative analysis to explore COVID-19 vaccine acceptance among diverse ethnic subgroups of Black Americans in the United States. This study investigates the responses of 79 African American, Afro-Caribbean, and African respondents over the age of 18 in Washington State and Texas between 2021-2022. Qualitative responses were analyzed by content category and ethnic subgroup. Of the 79 responses, 60 expressed favorable perceptions, 16 unfavorable, and 3 neutral. Dominant categories among participants in favor of the vaccine included personal health (26), concern for health of family/or community members (13), and desire to protect others (11). Among the 42 vaccinated African American respondents, the primary motivation was personal health (20). The 12 unvaccinated African American respondents cited fear of side-effects as the dominate motivation. Caribbean respondents cited family or elders as motivation for their decision. African respondents were nearly unanimous in taking the vaccine (13/16), citing trust in healthcare, protecting friends and family, and personal health as reasons. Community and personal relationships were critical decision-making factors in accepting the COVID-19 vaccine with African Americans having the strongest hesitancy.

Objective: To summarize the prevalence of PASC/Long COVID symptoms among the general population reported in published articles. This narrative review examined 21 PASC symptoms. Methods: A PubMed/manual search returned 114 articles on general PASC/Long COVID symptoms. Manuscripts were excluded if they were not research studies, didn’t report symptom prevalence, or used a pediatric population. Ninety-eight studies were selected for review and 59 met criteria for inclusion. Risk of bias was assessed with the Hoy critical appraisal tool. Results: After excluding studies with high risk of bias, meta-analysis of prevalence for 21 symptom categories ranged from 2.6-28.7% in studies based on surveys to 0.3%-7.1% in studies based on EHR data. Conclusions: PASC symptom studies are limited by variability in study design and representation of the general population. Further research is needed to effectively cluster symptoms in meaningful ways that enable focused treatment.

The main point in the present article was the comparison of the Technical Efficiency (TE) in four years for milk production in Ecuador by the period 2018 – 2021, before and after the pandemic, and the determination of the factors related to the TE for the last year. The information from the official public database in the country were analyzed by the nonparametric technique called DEA including a bootstrap simulation. Once different variables were selected including aspects as livestock and labor, the TE with Variable Returns to Scale (VRS) with “output” orientation was calculated by each year and province. Among the provinces, statistically significant differences were found (P<0.1) for the TE means, and most of the efficient units were found throughout the Andean zone, in each year. Between the most important findings, it was important that the TE average after the beginning of the pandemic was statistically lower than the last 3 consecutive years under study (P<0.1) with 3% approximately of decrease, and the main factors related to this were multiple including labor characteristics, the field composition, and the supplies access during the pandemic. Finally, some implications for public policy were found around the gender in agriculture activities, the social security, and the difficulties in supplies access.

There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. Often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub functions level. Therefore, we first aim to summarize current level of evidence supporting a negative impact of COVID-19 infection on cognitive functions. 27 studies have been included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3,786 healthy controls). We then performed a meta-analysis summarizing the results of 5 studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in Standardized Mean Differences, is -0.56 [95%CI -0.79 ; -0.34]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and to avoid long-term complication.

COVID-19 (SARS-Cov-2) is spreading around the globe in a highly contagious manner. China has shown the way to halt the progression of the disease by totally sealing Wuhan from rest of china but they could not prevent community spread resulting in more than 4000 deaths in a short period of time. India, following example of china, ordered national Lockdown early on 23 March, 2020. But it is difficult to determine the transition Here we have changed the way we look at available data to detect an early onset of the effect of Lockdown. Here a simple method is described for the first time to determine at the earliest when a change is beginning to take effect after Lockdown on the progression/regression of the spread of novel COVID-19 virus which could help to frame strategy for intervention to prevent community spread and save lives.

To mitigate the COVID-19 infection, many world governments endorsed the cessation of non-essential activities, such as the school attendance. Thereby, forcing the evolution of the teaching model to the virtual classroom. In the present work we show the application of a modified version of the adapted COVID-19 stress scales (ACSS) which also included teaching anxiety and preparedness, and resilience for academic professionals in Mexico, during the unprecedented transformation of the education system undergone in the COVID-19 quarantine. Most of the studied variables: gender, age, academic degree, household occupants, having a disease, teaching level, teaching mode, work hours, resilience, teaching anxiety and preparedness, and fear of being an asymptomatic patient (FOBAP), showed significant statistical correlation between each other (p<0.050) and to the 6 areas of the ACSS (danger, contamination, social economical, xenophobia, traumatic stress and compulsive checking). Our results further showed that the perceived stress and anxiety, fell into the category of absent to mild with only the danger section of the ACSS falling into the moderate category. Finally, resilience generated throughout the quarantine, seems to be a predictor of the adaptation the academic professional has undergone to cope with stress.

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.

The Novel Coronavirus Disease (nCOVID) has grabed the whole world recently since its origin in Wuhan city of China. There is very dire consequences the whole world is going through because of nCOVID. The unprecedented nCOVID and associated consequences pushed the public health system in the crisis. Undoubtedly, it has affected almost all countries of the world. Nevertheless, hardly a few country it has spared from its dire consequences in terms social and economical losses. However, it is worth of observing that some of the positive consequences are also results of this pandemic. Consequently, this paper discusses the pros and cons of the pandemic from various perspective such as social and economical impacts on human lives and livelihoods.

Background: Cigarette smoking (CS) is a global public health problem and a high-risk factor for various diseases. In December 2019, a novel coronavirus (HCoV-19) was identified in Wuhan, China. Because ACE2 has been identified as a receptor for HCoV-19, we hypothesize that CS affects the expression pattern of ACE2 in respiratory tract, causing differences in susceptibility to the virus. Methods: Three datasets (GSE994, GSE17913, and GSE18344), were downloaded from the Gene Expression Omnibus (GEO) database. Correlation and enrichment analysis were used to evaluate the function of ACE2. Also, the different expression of ACE2 in different groups of three datasets were analyzed. Results: Genes associated with ACE2 were enriched in important biological processes such as viral processes and immune response. Elevated ACE2 were found in intrapulmonary airways (GSE994) and oral epithelial cells (GSE17913) of smokers but not those of non-smokers or former smokers. Significant dose- and time-dependent relationships between CS and ACE2 expression were observed in mouse lung tissues, and long periods without smoking were found to significantly reduce ACE2 expression. Conclusions: Both human and rat data confirmed that CS could induce increased ACE2 in the respiratory tract, indicating that smokers have a higher susceptibility to HCoV-19.

The COVID-19 pandemic struck unexpectedly, emergency services and chronic care institutions, including dialysis centers, were overloaded. An important problem was the care of positive COVID patients, but also the care of chronically dialyzed patients who presented emergencies. In our Hospital, which has become a COVID support for dialysis patients with severe forms of the disease, we had to care for PD patients with dialysis-related emergencies. We presented 2 cases of patients managed on an outpatient basis or 1 day hospitalization, treated successfully and without compromising the quality of the care provided. We used remote monitoring, we worked in a multidiscipli-nary team, we shortened the hospitalization of patients (and implicitly the risk of contact). In pandemic conditions, the advantage of PD was represented by the possibility of patient isolation, so that in the first 6 months of the pandemic, we recorded no deaths in this category of patients. In case of hemodialysis patients, in-fection and mortality rates were high. Although we expected an increase in the number of peritoneal dialysis patients in the post-pandemic period, this did not happen. We continue to plead for the popularization of the PD method among patients and doctors, which has proven its advantages under the conditions of the pandemic.

Long Covid is a debilitating condition that has been well-documented over the past 4 years and shares many similarities with other post-viral chronic illnesses. Despite this, clinicians are not confident in recognising the signs of Long Covid, or effectively managing the symptoms of their patients. This paper presents a single patient case report from a biomedical researcher who has had Long Covid for 2 years; it is written in relatively plain language to be accessible to both patients and clinicians across multiple specialities. The author has had the ability and expertise to keep up with the Long Covid research literature, and from that has cobbled together a management strategy that has alleviated her own symptoms, and those of other people with whom she has shared her protocol. The author’s experience of developing and managing her Long Covid is presented here, in the hopes that it may be of assistance to clinicians in identifying and managing Long Covid in their own patients.

The last decade was characterized by the reduction of hospital beds throughout Europe. When facing Covid pandemic, this has been an issue of major importance as hospitals were seriously overloaded with an unexpected growth in demand. The dichotomy formed by the scarcity of beds and the need for acute care was handled by the Bed Management (BM) function. This study explores how BM was able to help the solidness of the healthcare system, managing hospital beds at best and recruiting others in different set-tings as intermediate care, in a large Local Health Authority (LHA) in central Italy. Ad-ministrative data show how the provision of appropriate care was achieved recruiting approximately 500 beds belonging to private healthcare facilities affiliated with the re-gional healthcare system and exercising at best the BM function. The ability of the system to absorb the extra demand caused by Covid was made possible using intermediate care beds, which allowed to stretch the logistic boundaries of the hospitals, and by the promptness of Bed Management in converting beds in Covid beds and reconverting them and timely managing internal patient logistic, thus creating space according to the healthcare demand.

Long COVID affects a significant number of people after acute coronavirus disease 2019 (COVID-19), and haematological changes can persist in the COVID-19 phase. This study aimed to evaluate these haematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a ‘long COVID’ clinical care programme in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected for quantification of erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalised in the acute phase had higher mean red/white cell, platelet, and plateletcrit levels and red cell distribution width. In addition, haematimetric parameters were higher in shorter periods of long COVID. Patients presenting with more than six concomitant long COVID symptoms had a higher white blood cell count, shorter prothrombin time (PT), and increased PT activity. Within up to 985 days of long COVID, our results suggest a probable benign compensation for erythrogram-related markers. Increased levels of leukogram-related markers and increased coagulation activity were observed in the worse long COVID groups, also indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.

In this paper, bikeshare data in Chicago on weather-friendly days in 2019 and 2020 were analyzed to investigate the variation in bikeshare travel before and during the pandemic. Our results show that bikeshare trips during the pandemic were much longer than prior to the pandemic. The increased rate of bikeshare usage was unbalanced spatially and varied significantly for different user types. Specifically, bikeshare was used significantly more by casual users than by subscribers, and the increase occurred much more in the outskirts of the city. The increase in bikeshare travel was associated with a reduction in travel by ride-hailing and public transit, especially in the urban periphery. The correlation of bikeshare use with the bus system was much less significant than with the rail system. Bike lanes/facilities had a mixed effect on bikeshare travel. Weekend bike trips increased in areas where there was no bike lane. Weekday trips, on the contrary, increased in the vicinity of bike greenways.

The interleukin 6 (IL-6) receptor blocking antibody tocilizumab was repurposed in the coronavirus pandemic with the intention of blocking the excess inflammatory activation associated with severe disease. We retrospectively evaluated the response to tocilizumab based on measured levels of IL-6 as well as other inflammatory markers. In the sample of 41 patients with measured levels, 16 received tocilizumab. In patients who received tocilizumab, there was a statistically significant relationship between both higher IL-6 levels and measured acute phase reactants with mortality, but not in those who did not. Additionally, an improved mortality after tocilizumab was suggested with those with higher IL-6 measurements, but not in those with lower levels, but this finding failed to achieve statistical significance (p=0.14). Though this study is limited by a small sample size and retrospective design, an association is suggested between higher IL-6 levels and improved mortality after tocilizumab.

OBJETIVES: During the COVID-19 pandemic, the risk of collapse of the health system created great difficulties. We will demonstrate that Intermediate Respiratory Care Units (IRCU) provide adequate management of patients with non-invasive respiratory support, which is particularly important in patients with SARS-CoV-2 pneumonia. METHODS: A prospective observational study of patients with COVID-19 admitted to the ICU of a tertiary hospital. Sociodemographic data, comorbidities, pharmacological, respiratory support, laboratory and blood gas variables were collected. The overall cost of the unit was subsequently analyzed. RESULTS: 991 patients were admitted, 56 to the IRCU (of the 81 a critical care unit). Mean age was 65 years (SD 12.8), Barthel Index 75 (SD 8.3), Charlson 3.1 (SD 2.2), HTN 27%, COPD 89% and obesity 24%. Significant relationship (p <0.05) with higher mortality of the following: fever greater than or equal to 39oC [OR 5.6; 95% CI (1.2-2.7); p = 0.020], protocolized pharmacological treatment [OR 0.3; 95% CI (0.1-0.9); p = 0.023] and IOI [OR 3.7; 95% CI (1.1-12.3); p = 0.025]. NIMV showed less of a negative impact [OR 1.8; 95% CI (0.4-8.4); p = 0.423] than IOI. The total cost of the IRCUs amounted to €66,233. The cost per day of stay in the IRCU was €164 per patient. The total cost avoided was €214,865. CONCLUSION: The pandemic has highlighted the importance of IRCUs in facilitating the management of a high patient volume. The treatment carried out in IRCUs is effective and efficient, reducing both admissions to and stays in the ICU.

Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

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.

Telehealth has been playing a progressively major role in the management of the NCOVID-19 crisis. The enforcement of social distancing measures has had the consequence of reduced technology distance in almost every walk of life. In this paper, based primarily on the still unfolding experiences of deploying it during the current situation, we argue that telehealth has finally come of age and that it is time to move it from the peripheries to the center of the 21st century healthcare. To provide a live context to the discussion, several instances of how telehealth strengthened our healthcare systems during the NCOVID-19 crisis are presented.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Background: There have been few reports of cutaneous skin lesions in severe COVID-19 hospitalized patients which exhibit different behavior compared to outpatients. Furthermore, a notable lack of rigorous studies exits. In this study we included patients with generalized rash during the first wave of the pandemic for characterization.Methods: Hospitalized patients with severe confirmed pulmonary COVID-19 infection and a generalized cutaneous rash during the first wave in March-May 2020 were included. The study received approval from the ethics committee. Clinical presentation, histo-logical examination, blood test, and complete blood interleukin profile were assessed. Special immunohistochemical investigations were conducted. Long term follow-up of the patient was performed throuhg a phone call 24 months later. Results: A total 28 patients were studied and classified by histological examination into three groups: G1: perivascular dermatitis (18/28, 64%); G2: Drug reaction (7/28, 25%); and G3: Generalized exanthema and chilblain (3/28, 11%). The virus was not detected in the skin, by PCR and by immunohistochemical analysis, and the interleukin expression in the skin were undetectable results. Vascular cell adhesion molecule 1 (VCAM1), E-selectine, and IT Galpha 5 were unspecific. G1 exhibited the least inflammation, G2 the most in-flammatory, and G3 had previous inflammation. Discussion: Our data suggest that generalized exanthemas during severe SARS-Cov-2 infection exhibit unspecific finding and are similar to other rashes caused by inflammation. Drug reaction should be considered, as they accounted for 25% of the rashes. Further studies including higher number of patients are necessary.

The collective considerations presented here lead to a crucial question: What truly constitutes the primary public health challenge posed by SARSCoV-2 infection and its variants?The findings of Bowen et al.(1) and Noé et al.(4) have offered us new insights into the actual repercussions of SARSCoV-2 virus infections on public health. They unmistakably point to the late sequelae and complications arising as secondary effects of the viral infection, causing severe and long-term damage to global public health. Rather than the acute infection which has a very low mortality rate in the general population, as initially and commonly believed.

Global research on the Covid-19 vaccine’s effectiveness is using methods that are misleading the scientific community and public opinion. There is a golden rule in medicine: to measure the effectiveness of an experimental medicine you need to have two groups. The group that will take medicine and the group that will not take medicine. You follow the health status of both groups for a few months and you will get objective results. This is the only proper methodology to verify the effectiveness of a new medicine. Articles cited from 1-5 did not use the gold rule. They develop different kinds of methodologies that all have no statistical significance. On the basis of their methodologies, they conclude that Covid-19 vaccines have a positive effect on public health. By comparing graphs of the intensity of vaccination and the rate of mortality we see that after the period of intense vaccination follows the period of higher excess mortality. Basic statistical data are confirming that Covid-19 vaccines increased the mortality rate.

Medical surveillance and risk mitigation protocols to reduce viral transmission have underpinned the return of elite football during the COVID-19 pandemic. This article describes the evidence-informed approach and surveillance findings from the English Football League across a 9-week period at the end of the 2019-20 season. Protocols were devised by the lead EFL Medical Advisor with specialist occupational medicine input. Isolation requirements for cases and contacts were in-line with UK Government regulations, with external contact tracing conducted by local public health authorities. Quantitative PCR testing was conducted twice weekly and within 72 hours of fixtures. 43 individuals, including 18 players returned positive tests. No positive results were returned after week 5 (round 10). Our findings support those from other leagues that with appropriate compliance, elite football can continue safely during this pandemic. We recommend that protocols and compliance should be revised as necessary according to community prevalence and changes in viral transmission dynamics.

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.

Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question as to whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known ‘risk factors’ for AF, and in particular exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots are cytotoxic by inducing hypoxia/reperfusion and other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.

HIV/AIDS and COVID-19 discourses are often compared; however, theorizing them together in terms of political efficacy and possibility is more novel. The collective of academics, activists, artists, and others–What Would an HIV Doula Do? (WWHIVDD) which for years has responded to the HIV/AIDS pandemic, has turned their attention to experiences of living with COVID-19. Through a qualitative analysis of two texts–a zine and a guide for authors writing about these pandemics–that specifically address experiences of/with COVID-19 by WWHIVDD, we examine how HIV/AIDS and COVID-19 discourses can productively be considered as chronic illness/COVID discourses that have the potential for more fruitful collective/political action and scholarly theorization of people living with pandemics.

COVID-19 affected health and wellbeing globally. Graduating nursing students face a variety of stressors and entering the nursing profession during the pandemic added additional stress. Mood, perceived stress, resilience, and coping were assessed in an Australian sample of 112 graduating nursing students, who completed the Brunel Mood Scale (BRUMS), Perceived Stress Scale (PSS-4), and Brief Resilient Coping Scale (BRCS). Mean BRUMS scores for tension, fatigue, and confusion were significantly above population norms, and vigour scores significantly below. Mean PSS-4 scores were reflective of population norms, but showed higher levels of stress for younger and on-campus students compared to those who were older or who studied externally. BRCS data showed that 82.1% of the graduating nursing students were medium or high resilient copers. Mood profiles suggested that 19.6% of participants had elevated mental health risk, 23.2% showed potential risk of burnout, and only 17.9% reported mood profiles associated with positive mental health. High mean tension scores reported by the graduating nursing students indicated apprehension about joining the profession, although stress, resilience and coping scores suggested they were adequately managing the additional stressors generated by a global pandemic.

The pandemic was an enormous experience all over the world. The type of living, working and study were changed irreversibly. Facing the opportunity to establish old frames of education in universities is impossible. The adoption of new ways of teaching and assessments reveal their convenience and in the same way their weak points. In response to that stage, on 14 December 2022, the EU parliament accepted the "Digital Decade Policy Programme 2030", for the establishment of a digital transformation community (EU 2022). Trakia University had an online assessment system, quizzes for self-training, and final exams, developed in 2008 on Moodle virtual learning environment. During the pandemic, online exams and lectures were conducted using platforms like BigBlueButton in Moodle or Google Meets. The article gives the results of online exams before, during, and after the pandemic. The outcome, without doubt, displays the lowering knowledge level or performance during the social isolation due to COVID-19, and after, and the reasons are discussed. During the second year of the pandemic was mentioned also a high dropout of students. Now the situation is returning to the previous levels, before the pandemic, but the quality of education is not yet reached. The article values the grades results of session exams and has the intention to clarify the influence of the pandemic period on the excellence of high institution education.

Researchers and organizations are pursing 100 Day Vaccine Development to reduce the impact of any new pandemic-causing virus. They propose monitoring viral emergence and developing vaccines for discovered viruses which would undergo safety testing in humans. If one of these viruses emerges, phase III trials would then take place. There are two problems with this approach - first, phase III trials are too long for the 100-day goal and second, the virus that emerged might not have been discovered in their surveillance. An alternative approach would be to first develop vaccines for viral families similar to the pan coronavirus vaccines being proposed for next generation COVID vaccines. Phase III trials for them would be run even if a virus in the family wasn’t having an outbreak. If a virus in a family for which a vaccine has been developed has an outbreak and the phase III trialed vaccine is not effective against it, develop a booster based on the phase III trialed vaccine. Since booster development and approval takes less than 100 days, the 100 Day Vaccine Development goal would be met.

Background. The SARS-CoV-2pandemic has become the greatest public health challenge worldwide. Intensive research started to develop vaccines and by the late 2020 vaccination campaign started. Objective. Collecting information from European countries, how and in what extent were family physicians/general practitioners/FPs/GPs involved in the vaccinations-campaign in 2021 and how was it organized at national level. Method. A short questionnaire was distributed through the secretariats of WONCA-Europe and the European Forum for Primary Care. Results. In most of the countries participation of FPs/GPs was compulsory. The vaccination was usually centrally organized by governmental authorities. At the beginning (web-based) registration of patients was required, mainly at national level. By the mid of 2021, vaccination on walk in basis became available in almost every country for the first and for the booster injections. The remunerations of GPs/FPs were differed, in some countries without extra payment. The Pfizer’s vaccine was used in all countries; while in 9 countries not EMA approved vaccines were also used in primary care settings and at vaccination centres. In some countries, professional homepages helped the GPs. The involvement of PHC providers did not correlate to the vaccination coverage of the entire population of the respective countries. It was the highest in the more developed countries with higher living standard, where participation of GPs was voluntary and appropriate financial incentives were offered for them. Conclusion. The vaccination campaign was a professional and logistic challenge and an excellent performance of PC providers. Experiences gained could be used in the future to manage similar pandemic challenges.

The Covid 19 pandemic threaten the life of individuals and there was a lack of information in treatment, handling of patients and disposal of waste. The psychological and behavioral impact on Humans due to outbreak of Covid is studied and based on that a person-centered care center is suggested. The research methodology used are surveys, interviews among stake holders and design details of person-centered care center. Based on the surveys and interviews conducted during pandemic, it is found that 94% of the respondents prefer to use private vehicles with at least one member to ac-company them. People prefer to use 3 ply facemasks, followed by cotton masks and N95. Existing literature discusses the physical effects on the individual, but this paper focuses more on pros and cons on human life during the pandemic and lock down period. Based on the study, care center with facilities to treat patients with different levels of infections and counselling center for the persons suffered from Covid and other infectious diseases to overcome their psycho-logical and behavior changes are recommended.

Background: The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long Covid is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long Covid, living in communities recognised as more deprived. Methods: The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual ‘clinic’ was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual’s participation and their completion of the intervention. Results: Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long Covid difficulties. Conclusions: This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long Covid.

Abstract: Service polycentricism, in the face of the pandemic, took on a new significance because of sanitary requirements. Population concentrations in large service centres face a high risk of infection both at their destination and during the trip. Higher-tier services were largely closed during the threat’s peak. In this paper, the focus of the study has been placed on the urban scale of a large city’s polycentricism as seen through the prism of service concentrations, which, to a degree, are commuter destinations, but primarily act as attractors that are not associated with work—they satisfy higher-tier service needs. To formulate the investigative apparatus used to study the functio-spatial structure of Cracow. The current threat, as well as the high probability of similar situations happening in the future, will probably lead to changes in behaviour patterns of consumers and service providers in reference to siting. Local service centres that are accessible to pedestrians, due to safety-related considerations, can gain significant popularity.

COVID-19 induces coagulopathy at the base of SIC (sepsis-induced coagulopathy) and it is an important cause of death in the patients. Cytokine storm causes imbalance in coagulation and fibrinolytic system. A combination of hypercoagulability state, decrease or inhibition of fibrinolytic and endothelialopathy causes thromboembolic events. Underlined disease with a high rate of mortality in COVID-19 like diabetes, hypertension and some conditions like aging and obesity are the main disorders with hemostatic disturbance and increase of coagulopathy. Therefore, it seems that the combination of COVID-19 infection and these risk factors increase the risk of thromboembolic all together.

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

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (M^pro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 M^pro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 M^pro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 M^pro inhibitors. However, further research is necessary to investigate their potential medicinal use.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

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.

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have abnormally hard outer shell (low M disorder; i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far was found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2 especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 amd later in Omicron, is associated with attenuation according to the Shell-Disorder-Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.

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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological biomarkers of LongC, we investigated the soluble proteins present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected from 2020-2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1b was significantly increased in both nLongC and Cov and IL-8 elevated in only nLongC. Both brain-derived neurotropic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

SARS-CoV-2, the virus that causes theCOVID-19 disease, has been demonstrated to cause immune suppression in certain individuals. This can manifest as a reduced ability for the host's immune system to effectively control the infection. Studies have reported that patients with COVID-19 can exhibit a decline in white blood cell counts, including natural killer cells and T cells, which are integral components of the immune system's response to viral pathogens. These cells play critical roles in the immune response to viral infections, and their depletion can make it harder for the body to mount an effective defense against the virus. Additionally, the virus can also directly infect immune cells, further compromising their ability to function. Some individuals with severe COVID-19 pneumonia may develop a "cytokine storm," an overactive immune response that may result in tissue damage and organ malfunction. The underlying mechanisms of immune suppression in SARS-CoV-2 are not entirely comprehended at this time, and ongoing research is being conducted to gain a more comprehensive understanding. Research has shown that severe SARS-CoV-2 infection promotes the synthesis of IgG4 antibodies. In this work, we propose the hypothesis that the IgG4 antibody produced by B cells in response to infection by SARS-CoV2 generates immunological tolerance that prevents its elimination, and leads to persistence and chronic infection. In sum, we believe that this constitutes another immune evasion mechanism that bears striking similarities to that developed by cancer cells to evade immune surveillance.

Chronic diseases affect a disproportionate number of United States (U.S.) Veterans, causing significant long-term health issues and affecting entitlement spending. This longitudinal study examined the health status of U.S. Veterans as compared to non-Veterans pre- and post-COVID utilizing the annual Center for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System (BRFSS) survey data. Age-adjusted descriptive point estimates were generated independently for 2003 through 2021, while complex weighted panel data were generated from 2011 and onward. General linear modeling revealed that the average U.S. Veteran reports a higher prevalence of disease conditions except for mental health disorders when compared to the non-Veteran. These findings were consistent with both pre- and post-COVID, however, both groups reported a higher prevalence of mental health issues during the pandemic years. The findings suggest that there have been no improvements in reducing Veteran comorbidities to non-Veteran levels and that COVID adversely affected the mental health of both populations.

The Coronavirus disease-19 (COVID-19) pandemic dramatically impacted on oncologic patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated also for oncologic population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy de-livery were not available. We aimed to evaluate potential factors influencing the outcome of COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing COVID-19 vaccination with gas-tro-entero-pancreatic and neuroendocrine neoplasms, treated at our Institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection 86.9% received two-doses of Pfizer-BioNTech and the remains Moderna vaccine. All patients obtained a subsequent im-mune-response. A significantly lower values of IgG for patients treated with chemotherapy versus other anti-cancer agents (p=0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs >7 days from the last systemic treatment (p=0.77) and lymphocytes count (p=0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue but rather the quality of the subset of lymphocytes before the vaccination to deter-mine the efficacy level of immune-response in this population.

Neutrophils play an important role as the first line of innate immune defense. One function of neutrophils, called neutrophil extracellular traps (NETs), has been discovered recently. NETs are extensive fibrous structures released extracellularly from activated neutrophils in response to infection. They are composed of cytosolic protein assembled on a scaffold of released chromatin. These structures suppress the dissemination of micro-organisms in blood by trapping them mechanically, and by exploiting coagulant function to segregate them within the circulation. In addition, NET components (DNA, histone, and granule proteins) also contribute to the triggering of an inflammatory process. NET function, however, can be regarded as a double-edged sword. On one hand, NET formation is an efficient strategy for neutralizing invading micro-organisms. On the other hand, NET can be harmful to the host, as its exposed by-products that are toxic to endothelial cells and parenchymal tissue. We present here the analogous biological and physiological features of the harmful positive amplification loop between inflammation and tissue damage induced by NETosis dysregulation and Coronavirus Disease-2019 (COVID-19) pathogenesis. Considering the rapid evolution of this disease symptoms and its lethality, we hypothesize that COVID-19 progresses under an amplifier loop, leading to an massive, uncontrolled inflammation process. We also describe the correlations of COVID-19 symptoms and biological features with those consecutive to uncontrolled NET formation causing various sterile or infectious diseases. General clinical conditions, and numerous pathological and biological features, are analogous with NETs deleterious effects. We postulate that Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) induces a disproportionate virus-induced NET release, and that this plays a key role in COVID-19 pathogenesis. While neutrophils are the principal starting point for extracellular and circulating DNA release, targeting NETs rather than neutrophils themselves may stand for an effective strategy. This paper offers an in-depth review of NET formation, function and pathogenic dysregulation, as well as of current and future therapies to control NET unbalance. As such, it enables us also to suggest new therapeutic strategies to fight COVID-19. In combination with or independent of the latest tested approaches, we propose that, in the short term, deoxyribonuclease I (DNase-1) treatment should be evaluated; we also advocate a significant increase in research on the development of toll-like receptors (TLR) and C-type Lectin like receptors (CLEC) inhibitors, and on anti-IL26 therapies.

Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.

Health services research is a multidisciplinary discipline that aims to improve population health by studying healthcare services' organization, delivery, and financing. Over time, the field has worked to define its boundaries and establish a set of core research topics and methods addressing population wellbeing, access, quality, and cost. Although the influence of health technology is significant, our literature survey on health services research showed that SCs in general—containing their management, cost, and policy—had received little attention. Importantly, our assessment also showed that the system’s readiness to handle supply policy and supply device deficiencies like those encountered during pandemic was hardly ever mentioned. Reduced open areas and water bodies, deteriorating infrastructure, and changes in the biological morphology all affect cities’ uncontrollable and unplanned growth. Urban amenities, facilities, and healthcare services were unevenly distributed due to this unchecked urban population development. In light of this, this research suggests two reliable models for site selection issues for one of Hong Kong’s main hospitals. Levels of uncertainty, infeasibility tolerance, and reliability are taken into consideration. Then, two categories of uncertainty—symmetric and bound-ed—were examined. As a result, the challenge of scheduling in uncertainty has been considered, and potential solutions have been presented using a specified probability distribution function. The paper concludes by introducing the specific justice and health problems and outlining four typical strategies. In order to ensure that medications and other healthcare supplies are produced, distributed, and given to patients, a vast network of systems, components, and procedures must be effectively managed. This research contributes in this regard. Also, its grantee fairness in health systems and the populations health locally, nationally, and globally. It highlights health inequity, advances the measurement of health inequity, and promotes public dialogues on health inequity.

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.

Abstract Background COVID-19 vaccination program among Adults in India is one of the highly successful vaccination drives globally. Indian children aged 15–18 years old became eligible for COVID-19 vaccination on 3rd January, 2022 followed by 12-14 years old children on 16th March, 2022. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination for children in India. Aim To assess parental perceptions and intention to get COVID-19 vaccination for their children (aged<18 years), Materials and Methods A cross-sectional anonymous web-based survey was designed. Healthcare workers of a tertiary care institute in Eastern U.P. having any children aged <18 years were the study population. They were recruited through snowball sampling and were sent the study questionnaire in Google form through email and WhatsApp. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with socio-demographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior routine childhood immunization. Bi-variate analysis was performed to find out the predictors of child vaccination intention among the parents. Results A total of 388 healthcare workers parents (HCWPs) having A child < 18 years of age completed the survey. Mean age of the parents were 40.28 ±11.34 years with majority(97.0%) completing recommended 2 doses of COVIID-19 vaccine. Around 91% of the parents agreed that COVID-19 vaccines are important for child’s health whereas about 89% agreed to the statement that COVID-19 vaccines are effective. A total 356 (91.7%) participants were willing to vaccinate their child against COVID-19, 91.3% of them liked to do so as soon as possible. The factors significantly associated with the stated likelihood of child vaccination among the participants were younger age, female gender, urban residence, absence of any chronic illness, lower monthly income, history of COVID-19 in child and the child/children completed with routine childhood vaccines. Parental concerns mainly centered around vaccine need, safety and side effects. Conclusion The healthcare worker parents(HCWPs) have good knowledge and positive attitude towards COVID-19 vaccination for children. Around 92% of them were willing to vaccinate their children with COVID vaccine currently, which implies very low vaccine hesitancy among the HCWPs . Further longitudinal studies are required to be conducted to assess the trend of parental acceptance of COVID vaccine.

Background: Sudden changes in clinical practice and the altered ability to care for patients due to the COVID-19 pandemic have been associated with moral distress and mental health concerns in healthcare workers internationally. This study aimed to investigate the severity, prevalence, and predictors of moral distress experienced by Australian healthcare workers during the COVID-19 pandemic. Methods: A nationwide, voluntary, anonymous, single time-point, online survey of self-identified frontline healthcare workers was conducted between 27th August and 23rd October 2020. Participants were recruited through health organisations, professional associations or colleges, universities, government contacts, and national media. Results: 7846 complete responses were received from nurses (39.4%), doctors (31.1%), allied health staff (16.7%) or other roles (6.7%). Many participants reported moral distress related to resource scarcity (58.3%), wearing PPE (31.7%) limiting their ability to care for patients, exclusion of family going against their values (60.2%), and fear of letting co-workers down if they were infected (55.0%). Many personal and workplace predictors of moral distress were identified, with those working in certain frontline areas, metropolitan locations, and with prior mental health diagnoses at particular risk of distress. Moral distress was associated with an increased risk of adverse mental health outcomes. Feeling appreciated by the community mitigated this risk in healthcare workers. Conclusions: Safeguarding healthcare workforces during crises is important for both patient safety and workforce longevity. Targeted interventions are required to prevent or minimise moral distress and associated mental health concerns in healthcare workers during COVID-19 and other crises.

EGFR mutations are heterogenous but all carry the same weighting in the Lung-molGPA. The aim of this study was to elucidate the different prognostic implications of molecular subtypes and frontline TKIs in EGFR-mutated lung adenocarcinoma with synchronous brain metastases (BM) using the Lung-molGPA. Medical records were searched in hospital databases from 2011 to 2015. Patients with EGFR-mutated adenocarcinoma and brain metastases who received TKIs were included. The Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 256 patients were included with a median overall survival (OS) of 17.2 months. In multivariate analysis of OS, only age (70 versus &lt;70 years, HR:1.71, 95% CI:1.25-2.35, p&lt;0.001), KPS (&lt;70 versus 70, HR:1.71, 95% CI:1.26-2.31, p&lt;0.001), and rare mutations (other versus exon 19 deletions, HR:1.78, 95% CI:1.04-3.05, p=0.037) remained statistically significant. In patients with a Lung-molGPA score 2.5, EGFR molecular subtypes had different median OS (exon 19 deletions versus Leu858Arg versus other, 18.8 vs 12.4 vs 12.1 months, p=0.021). In conclusion, different molecular subtypes treated with frontline TKIs have different prognostic implications in the Lung-molGPA. Further prospective studies are warranted to validate these findings.

Background: SARS-CoV-2 infection has spread to over 200 countries since it was first reported in December of 2019. Significant country-specific variations in infection and mortality rate have been noted. Although country-specific differences in public health response have had a large impact on infection rate control, it is currently unclear as to whether evolution of the virus itself has also contributed to variations in infection and mortality rate. Previous studies on SARS-CoV-2 mutations were based on the analysis of ~ 160 SARS-CoV-2 sequences available until mid-February 2020.^{2, 3, 4, 5} By mid-April, > 550 SARS-CoV-2 sequences had been deposited in GenBank, and over 8,200 in the GISAID database. Methods: We performed a sequence analysis on 474 SARS-CoV-2 genomes submitted to GenBank up to April 11, 2020 by multiple alignment using Map to a Reference Assembly and Variants/SNP identification. The results were verified on a larger scale, 8,126 hCoV-19 (SARS-CoV-2) sequences from GISAID database. Results: We identified 5 recently emerged mutations in many isolates (up to 40%). Our analysis highlights 5 frequent new mutations that have emerged since late February 2020. These mutations are: one each missense (non-synonymous) mutation in orf1ab (C1059T), orf3 (G25563T) and orf8 (C27964T), one in 5’UTR (C241T), one in a non-coding region (G29553A). The final mutation (G29553A) was found to be almost exclusive to the US isolates. The first 3 mutations are non-synonymous, leading to amino acid substitutions in the viral protein sequence. Except for C241T, all the novel mutations identified are absent in the isolates from Italy and Spain in the SARS-CoV-2 genomes deposited in GenBank and GISAID by April 13, 2020. Conclusion: The results of current study indicate that new mutations are emerging as COVID-19 pandemic are spreading to different countries and that geography specific mutants may exist. The findings of current study lay the foundation for further investigation into the impact of SARS-CoV-2 mutations on disease incidence, severity, and host immune response. In addition, it may also provide insights into vaccine development and serological response detection for the virus.

In the wake of the novel coronavirus, SARS-CoV-19, the world has undergone a critical situation in which grave threats to global public health emerged. Among human populations across the planet, travel restraints, border enforcement measures, quarantine, and isolation provisions were implemented in an attempt to control and limit the spread of the contagion. Decisions on how to implement and enforce various control policies should be determined based on available real-world evidence and theoretical prediction. In this study, we propose a novel exportation- importation epidemic model associated with the quarantine and hospitalized-isolation policies by considering the two-body system: a source country of a contagious disease and a neighboring country that is initially disease-free. The model is first applied to the original COVID-19 data in China, Italy, and the Republic of Korea (ROK) and observed through consistent fitting results with equivalent goodness-of-fit. Then, the data are estimated per the fitting parameters. Driven by these parametric settings and considering the normalized population, the numerical analysis, and epidemiological exploration, this work further elucidates the substantial impact of quarantine policies, healthcare facilities, and the public counter-compliance effect.

We describe the genomes of two Echovirus isolates from Nigeria as reference enterovirus species B genomes for the region. These Echovirus 7 and 19 genomes have 7,411nt and 7,426nt, and were recovered from sewage contaminated water (in 2010) and an acute flaccid paralysis case (in 2014), respectively.

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits. In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored. For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans. In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers. Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.

Long COVID-19 syndrom appears after Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) infection with acute damages to microcapillaries, microthombi and endotheliitis. However, the mech-anisms involved in these processes remain to be identified. All blood vessels are lined with a monolayer of endothelial cells called vascular endothelium of which one of the major properties is to prevent coagulation. VE cadherin is a component of endothelial cell junctions responsible for maintenance of the integrity of the vessels through homophilic interaction of its Ca++- dependent adhesive extracellular domain. We first provide evidence that VE-cadherin is a target in vitro for ACE2 cleavage because its extracellular domain (hrVE-ED) contains two amino acid sequences for ACE2 substrate recognition at the po-sitions 256P-F257 and 321PMKP-325L. Indeed, incubation of hrVE-ED with the active ecto-peptidase hrACE2 for 16 hrs in the presence of 10M ZnCl2 showed a dose-dependent (from 0.2 ng/ul to 2 ng/ul) decrease of the VE-cadherin immunoreactive band. In vivo, in the blood from patients having severe COVID-19, a circulating form of ACE2 was detected with an apparent molecular mass of 70 kDa while it was barely detectable in patients with mild infection. Of importance, in the patients with severe COVID-19 disease, the presence of three soluble fragments of VE-cadherin (70, 62, 54 kDa) were detected using the antiEC1 antibody while only the 54 kDa fragment was present in patients with mild disease. Altogether, these data clearly support a role for ACE2 on VE-cadherin cleavage leading to potential biomarkers in SARS-CoV2 infection related with the vascular disease in “Long COVID-19”.

Despite offering free-of-charge COVID-19 vaccines starting July 2021, Guatemala has one of the lowest vaccination rates in Latin America. During September 28, 2021 to April 11, 2022, we conducted a cross-sectional survey of community members adapting a CDC questionnaire to evaluate COVID-19 vaccine access and hesitancy. Of 233 participants ≥12 years, 127 (55%) received >1 dose of COVID-19 and 4 (2%) reported prior COVID-19 illness. Persons ≥12 years old unvaccinated (n=106) were more likely to be female (73% vs 41%, p<0.001) and homemakers (69% vs 24%, p<0.01) compared with vaccinated participants (n=127). Among those ≥18 years, the main reported motivation for vaccination among vaccinated participants was to protect the health of family/friends (101/117, 86%); 40 (55%) unvaccinated persons reported little/no confidence in public health institutions recommending COVID-19 vaccination. Community- and/or home-based vaccination programs, including vaccination of families through the workplace, may better reach female homemakers and reduce inequities and hesitancy.

Current generation witnesses a huge interest in optical waveguide due to their salient feature such as low cost, immune to electromagnetic interference, easy to multiplex, compact size, etc. These features of the optical fibers makes it an useful tool for various sensing applications including medicine, automotive, biotechnology, food quality control, aerospace, physical and chemical monitoring etc. Among all the reported application, the device has been widely exploited to measure the physical and chemical variation in surrounding environment. Optical fiber based temperature sensor plays a crucial role in this decade to detect high fever and tackle COVID like pandemic. Recognizing the major developments in the field of the optical fibers, this article aims to provide recent progress in temperature sensor utilizing several sensing configuration including standard fiber, photonic crystal fiber, and Bragg grating fibers. Additionally, the article also highlights the advantages, limitations, and future possibilities in this area.

The growth of the fаshion industry in Bаndung, which is increаsing every yeаr, if it is not bаlаnced with the аpplicаtion of digitаlizаtion аnd the use of the lаtest technology, it would be very unfortunаte. Аpаrt from the increаse in the number of internet users, the online shopping style by the community is аlso one of the driving forces for the growth of e-commerce, especiаlly in the midst of the current Covid pаndemic situаtion. This study will exаmine the аdoption of e-commerce technology to sell online in the midst of the Covid pаndemic to fаshion industry plаyers in Bаndung using these vаriаbles: effort expectаncy, performаnce expectаncy, fаcilitаting conditions, sociаl influence, existing hаbits, hedonic motivаtion, and also the price vаlue in the UTАUT2 model. So thаt it cаn show how the contribution of the аdoption of e-commerce technology to the behаviourаl intention аnd use behaviour of the fаshion industry consumers in Bаndung. Our research use quаntitаtive approach, cаusаl research/study with Structurаl Equаtion Modeling (SEM) аnаlysis technique using the SMАRTPLS 3.2.9 softwаre. Reseаrchers chose the аccidentаl sаmpling with а totаl of 400 respondents. Аll exogenous vаriаbles аffect behаviourаl intention by 80.9% аnd 54.9% on use behаviour.

The propagation of the coronavirus disease 2019 (COVID-19) reshaped the relationship between income and food-away-from-home (FAFH) expenditure in Mexico during 2020. Although the number of households participating in this market fell across income deciles and regions due to the pandemic, the impact on their budget shares is not uniform. Using data from the Encuesta Nacional de Ingresos y Gastos de los Hogares (ENIGH) 2020, we estimated an Engel curve of the Working-Lesser functional form for FAFH. Among the independent variables are the number of family members 65 years of age and older, and dummies to indicate whether the household experienced food insecurity or received remittances. The estimation was carried out following the Heckman two-step method, suitable for censored-response data. The results suggest that the budget share for FAFH drops as income increases. The number of older adults and food insecurity discourage the decision to participate in FAFH expenditure and increase its budget share, whereas remittances encourage participation and reduce its budget share. The corrected conditional elasticity is 0.4609; the sign and the magnitude indicate that FAFH is a necessity good.

Recently, several reports have emerged describing the long-term consequences of COVID-19 that may affect multiple systems, suggesting its chronicity. As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients discharged from the TCH, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p<0·00001). Women were more prone than men to develop long-term symptoms and invasive mechanical ventilation also increased the frequency of symptoms at 30-days post-discharge. Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.