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Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed a threat to society worldwide. The aim of the study was to analyze changes in the physical fitness of 11- to 15-year-olds during the COVID-19 pandemic. Methods: Cross-sectional research was conducted in randomly selected schools in Kraków (Poland) during the years 2020 and 2022. The study group included 1635 adolescents aged 11–15 years. The results of fitness tests such as flexibility, standing broad jump, handgrip strength, overhead medicine ball throw, shuttle run (10 × 5 m), and 30-second sit-ups were analyzed. Body height and weight measurements were also taken. The standing broad jump and handgrip strength were normalized. A statistical analysis was performed to compare the differences between groups using 2-way analysis of variance with the Tukey HSD post hoc test or Kruskal–Wallis test. Results: The test results revealed a deterioration decrease in sit-ups, standing broad jump, shuttle run, and normalized standing broad jump in both sexes. Furthermore, the test results among girls showed a decrease in overhead medicine ball throw and flexibility. An increase in test results of both sexes was noticed in handgrip strength of the right and left hand. Among boys in 2022, the results were better in the flexibility test and overhead medicine ball throw compared with their peers from 2020. Conclusion: This study indicates a decrease in overall physical fitness in adolescents. The observed results may be associated with a decrease in physical activity, changes in nutrition, and restrictions imposed during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 caused major disruptions across the super-aged nation of Japan, yet few studies explored temporal changes among middle-aged and older cohorts from baseline to the height of community transmission. Changes in physical activity and sedentary behavior during global pandemics may alter patterns of morbidity and mortality among susceptible aging populations. Objectives: This study investigated patterns of physical activity, sitting behavior, and health among representative samples of middle-aged and older adults in Tokyo before and during the pandemic. Methods: Repeated online surveys were conducted with quota samples of 800 Tokyo residents in 2019 and 2021 using validated Japanese-language measures, including the short form-International Physical Activity Questionnaire and the Basic Ecological Health Scale-6. Statistical analyses included comparative evaluations of activity parameters by age cohort, gender, and selected covariates. Statistical tests included the Kruskal–Wallis test, Mann–Whitney U test, chi-square test for Independence and Hierarchical Regression. Results: Over 34% of respondents were inactive at each data collection point, and 72% reported negative impacts of COVID-19 on their physical activities. Older adults showed no significant changes in their activity and sitting behavior and reported better health compared with those in middle age across the pandemic. Middle-aged males reported a significant decline in total activity of 33% across the pandemic period (U = 16,958, z = −2.64, p =.008, r =.13). Middle-aged females reported the lowest levels of physical activity, and health, and showed a 29% increase in sitting behavior across the pandemic (U = 16,925, z = −2.68, p =.007, r =.13). Subjective health status was consistently associated with higher overall activity and walking before and during the pandemic. Conclusion: Differential outcomes were identified between age and gender regarding health, physical activity, walking, and sitting across the pandemic with significantly worse impacts reported among middle-aged samples. Implications: These results have implications for healthy transitions to later life and the design of postpandemic interventions to address activity opportunities in Japan. [ABSTRACT FROM AUTHOR]

Background: Although 24-hour movement behaviors are known to be interconnected, limited knowledge exists about whether change in one behavior during the COVID-19 pandemic (eg, increased screen time) was associated with change in another (eg, reduced physical activity or sleep). This review estimates mediational associations between changes in children's physical activity, screen time, and sleep during the COVID-19 pandemic. Methods: We included studies published between January 1, 2020 and June 27, 2022, in the PubMed/MEDLINE, Embase, PsycINFO, SPORTDiscus, and Web of Science databases. Summary data were extracted from included studies and analyzed with random-effects meta-regression. Results: This review included 26 studies representing 18,959 children across 18 mid-high-income countries (53% male; mean age, 11.5 [2.9] y). There was very good evidence of decreased total daily physical activity (factor change, 0.62; 90% CI, 0.47–0.81) and strong evidence of increased screen time (1.56; 90% CI, 1.38–1.77). There was very good evidence of decreased moderate to vigorous physical activity (0.75; 90% CI, 0.62–0.90) and weak evidence of increased sleep (1.02; 90% CI, 1.00–1.04). Mediational analysis revealed strong evidence that most of the reduction in total daily physical activity from before, to during, the pandemic was associated with increased screen time (0.53; 90% CI, 0.42–0.67). We observed no further mediational associations. Conclusion: Increased reliance on and use of screen-based devices during the COVID-19 pandemic can be linked with reduced child and adolescent physical activity. This finding links COVID-related restrictions to potential displacement effects within child and adolescent 24-hour movement behavior. [ABSTRACT FROM AUTHOR]

Background: Active school transportation (AST) is an important source of physical activity for children and a potentially important climate change mitigation strategy. However, few studies have examined factors associated with AST in the context of the COVID-19 pandemic. Methods: We used baseline data from a longitudinal survey to investigate correlates of AST during the second wave of COVID-19 (December 2020). We collected survey data from 2291 parents of 7- to 12-year-olds across Canada and linked this information with data on neighborhood walkability and weather from national databases. We assessed potential correlates representing multiple levels of influence of the social–ecological model. We used gender-stratified binary logistic regression models to determine the correlates of children's travel mode to/from school (dichotomized as active vs motorized), while controlling for household income. We examined the correlates of travel mode for both the morning and afternoon trips. Results: Consistent correlates of AST among Canadian children during the COVID-19 pandemic included greater independent mobility, warmer outdoor temperature, having a parent who actively commuted to work or school, living in a household owning fewer vehicles, and living in a more walkable neighborhood. These findings were largely consistent between boys and girls and between morning and afternoon school trips. Conclusions: Policymakers, urban planners, and public health workers aiming to promote AST should focus on these correlates while ensuring that neighborhoods are safe for children. Future research should monitor the prevalence and correlates of AST as COVID-19 restrictions are removed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hong Kong enforced stringent travel restrictions during the COVID-19 pandemic. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. METHODS: Retrospective cohort study summarising the characteristics of imported cases detected in Hong Kong between 13 November 2020 and 31 January 2022, when compulsory quarantine was implemented. FINDINGS: A total of 2269 imported COVID-19 cases aged 0-85 years were identified, of which 48.6 % detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than in ancestral strain and other variants cases (12 days; p

The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2s usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimers opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.

In the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, epithelial populations in the distal lung expressing Angiotensin-converting enzyme 2 (ACE2) are infrequent, and therefore, the model of viral expansion and immune cell engagement remains incompletely understood. Using human lungs to investigate early host-viral pathogenesis, we found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations. Human alveolar macrophages (AMs) reliably expressed ACE2 allowing both spike-ACE2-dependent viral entry and infection. In contrast to Influenza A virus, SARS-CoV-2 infection of AMs was productive, amplifying viral titers. While AMs generated new viruses, the interferon responses to SARS-CoV-2 were muted, hiding the viral dissemination from specific antiviral immune responses. The reliable and veiled viral depot in myeloid cells in the very early phases of SARS-CoV-2 infection of human lungs enables viral expansion in the distal lung and potentially licenses subsequent immune pathologies.

Coping with the COVID-19 pandemic had implications for athletes' mental well-being. This mixed-methods study examined the influence of self-compassion on athletes' coping during the pandemic through the mediator of cognitive appraisal. The prospective design involved 90 athletes completing two online surveys 1 week apart measuring self-compassion, cognitive appraisal, and coping strategies. The PROCESS macro was used for the mediation analysis. A qualitative thematic analysis was used to explore athletes' responses to the pandemic during the second survey. Self-compassion had an indirect negative effect on avoidance-focused coping by appraising the pandemic as less of a threat (95% confidence interval [−0.20, −0.001]) and had a total effect on emotion-focused coping (95% confidence interval [0.02, 0.40]). Based on the thematic analysis, athletes described many raw emotions and a variety of coping strategies during the pandemic. Self-compassion demonstrated promising benefits to athletes who dealt with the challenging situation of the pandemic. [ABSTRACT FROM AUTHOR]

COVID-19 infection is associated with a variety of vascular occlusive morbidities. However, a comprehensive understanding of how this virus can induce vascular complications remains lacking. Here, we show that a peptide fragment of SARS-CoV-2 spike protein, S192 (sequence 192-211), is capable of forming amyloid-like aggregates that can induce agglutination of red blood cells, which was not observed with low- and non-aggregated S192 peptide. We subsequently screened eight amyloid-binding molecules and identified BAM1-EG6, a benzothiazole amphiphile, as a promising candidate capable of binding to aggregated S192 and partially inhibiting its agglutination activity. These results provide new insight into a potential molecular mechanism for the capability of spike protein metabolites to contribute to COVID-19-related blood complications and suggest a new therapeutic approach for combating microvascular morbidities in COVID-19 patients.

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs1-3 and revealed how quickly viral escape can curtail effective options4,5. When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab4-6. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination4 and is challenging to replace with existing approaches. Rapidly modifying such high-value antibodies to restore efficacy against emerging variants is a compelling mitigation strategy. We sought to redesign and renew the efficacy of COV2-2130 against Omicron BA.1 and BA.1.1 strains while maintaining efficacy against the dominant Delta variant. Here we show that our computationally redesigned antibody, 2130-1-0114-112, achieves this objective, simultaneously increases neutralization potency against Delta and subsequent variants of concern, and provides protection in vivo against the strains tested: WA1/2020, BA.1.1 and BA.5. Deep mutational scanning of tens of thousands of pseudovirus variants reveals that 2130-1-0114-112 improves broad potency without increasing escape liabilities. Our results suggest that computational approaches can optimize an antibody to target multiple escape variants, while simultaneously enriching potency. Our computational approach does not require experimental iterations or pre-existing binding data, thus enabling rapid response strategies to address escape variants or lessen escape vulnerabilities.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2 variants capable of breakthrough infections have attracted global attention. These variants have significant mutations in the receptor-binding domain (RBD) of the spike protein and the membrane (M) protein, which may imply an enhanced ability to evade immune responses. In this study, an examination of co-mutations within the spike RBD and their potential correlation with mutations in the M protein was conducted. The EVmutation method was utilized to analyze the distribution of the mutations to elucidate the relationship between the mutations in the spike RBD and the alterations in the M protein. Additionally, the Sequence-to-Sequence Transformer Model (S2STM) was employed to establish mapping between the amino acid sequences of the spike RBD and M proteins, offering a novel and efficient approach for streamlined sequence analysis and the exploration of their interrelationship. Certain mutations in the spike RBD, G339D-S373P-S375F and Q493R-Q498R-Y505, are associated with a heightened propensity for inducing mutations at specific sites within the M protein, especially sites 3 and 19/63. These results shed light on the concept of mutational synergy between the spike RBD and M proteins, illuminating a potential mechanism that could be driving the evolution of SARS-CoV-2.

BACKGROUND: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. METHODS: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. RESULTS: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. CONCLUSIONS: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.

In pandemic scenarios involving novel human pathogenic viruses, it is highly desirable that vaccines induce strong neutralizing antibodies as quickly as possible. However, current vaccine strategies require multiple immunization doses to produce high titers of neutralizing antibodies and are poorly protective after a single vaccination. We therefore wished to design a vaccine candidate that would induce increased protective immune responses following the first vaccine dose. We hypothesized that antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein could be increased by drawing upon immunity to a previous infection. We generated a fusion protein containing the influenza H1N1 PR8 virus nucleoprotein (NP) and the SARS-CoV-2 spike RBD. Mice with or without preexisting immunity to PR8 were then vaccinated with NP/RBD. We observed significantly increased SARS-CoV-2 neutralizing antibodies in mice with PR8 immunity compared to mice without preexisting PR8 immunity. Vaccination with NP/RBD protected mice from SARS-CoV-2-induced morbidity and mortality after a single dose. Additionally, we compared SARS-CoV-2 virus titers in the lungs and nasal turbinates 4 days post-challenge of mice vaccinated with NP/RBD. SARS-CoV-2 virus was detectable in the lungs and nasal turbinate of mice without preexisting PR8 immunity, while SARS-CoV-2 virus was completely undetectable in mice with preexisting PR8 immunity. We also found that CD4-positive T cells in mice with preexisting immunity to PR8 play an essential role in producing the increased antibody response against RBD. This vaccine strategy potentially can be modified to target other pathogens of concern and offers extra value in future pandemic scenarios.IMPORTANCEIncreased globalization and changes in human interactions with wild animals has increased the likelihood of the emergence of novel viruses with pandemic potential. Vaccines can be effective in preventing severe disease caused by pandemic viruses. However, it takes time to develop protective immunity via prime-boost vaccination. More effective vaccine designs should quickly induce protective immunity. We propose leveraging preexisting immunity to a different pathogen to boost protection against emerging viruses. We targeted SARS-CoV-2 as a representative pandemic virus and generated a fusion protein vaccine that combines the nucleoprotein from influenza A virus and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Our vaccine design significantly increased the production of RBD-specific antibodies in mice that had previously been exposed to influenza virus, compared to those without previous exposure. This enhanced immunity reduced SARS-CoV-2 replication in mice. Our results offer a vaccine design that could be valuable in a future pandemic setting.

Coronavirus genomes have evolutionary histories shaped extensively by recombination. Yet, how often recombination occurs at a cellular level, or the factors that regulate recombination rates, are poorly understood. Utilizing experimental co-infections with pairs of genetically distinct coronaviruses, we found that recombination is both frequent and rare during coinfection. Recombination occurred in every instance of co-infection yet resulted in relatively few recombinant RNAs. By integrating a discrete-time Susceptible-Infected-Removed (SIR) model, we found that rates of recombination are determined primarily by rates of cellular co-infection, rather than other possible barriers such as RNA compartmentalization. By staggering the order and timing of infection with each virus we also found that rates of co-infection are themselves heavily influenced by genetic and ecological mechanisms, including superinfection exclusion and the relative fitness of competing viruses. Our study highlights recombination as a potent yet regulated force: frequent enough to ensure a steady influx of genetic variation but also infrequent enough to maintain genomic integrity. As recombination is thought to be an important driver of host-switching and disease emergence, our study provides new insights into the factors that regulate coronavirus recombination and evolution more broadly.

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior IgG anti-receptor-binding domain (RBD) and neutralization response against the Alpha and Delta variants when administered to individuals with a previous infection by SARS-CoV-2. The booster dose spiked the neutralization activity among individuals with and without a prior SARS-CoV-2 infection. The ChAdOx1-S vaccine induced weaker antibody responses in infection-naive subjects. A follow-up of 4 months post-vaccination showed a drop in antibody titre, with about 20% of the infection-naive and 100% of SARS-CoV-2 pre-exposed participants with detectable neutralization capacity against Alpha pseudovirus (Alpha-PV) and Delta PV (Delta-PV). Our observations support the use of different vaccines in a country with high seroprevalence at the vaccination time.

BackgroundCystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelination and remyelination.MethodsWildtype controls and Cst7-/- mice were intracranially (i.c.) infected with a sublethal dose of the neurotropic JHM strain of mouse hepatitis virus (JHMV), with disease progression and survival monitored daily. Viral plaque assays and qPCR were used to assess viral levels in CNS. Immune cell infiltration into the CNS and immune cell activation were determined by flow cytometry and 10X genomics chromium 3' single cell RNA sequencing (scRNA-seq). Spinal cord demyelination was determined by luxol fast blue (LFB) and Hematoxylin/Eosin (H&E) staining and axonal damage assessed by immunohistochemical staining for SMI-32. Remyelination was evaluated by electron microscopy (EM) and calculation of g-ratios.ResultsJHMV-infected Cst7-/- mice were able to control viral replication within the CNS, indicating that cystatin F is not essential for an effective Th1 anti-viral immune response. Infiltration of T cells into the spinal cords of JHMV-infected Cst7-/- mice was increased compared to infected controls, and this correlated with increased axonal damage and demyelination associated with impaired remyelination. Single-cell RNA-seq of CD45 + cells enriched from spinal cords of infected Cst7-/- and control mice revealed enhanced expression of transcripts encoding T cell chemoattractants, Cxcl9 and Cxcl10, combined with elevated expression of interferon-g (Ifng) and perforin (Prf1) transcripts in CD8 + T cells from Cst7-/- mice compared to controls.ConclusionsCystatin F is not required for immune-mediated control of JHMV replication within the CNS. However, JHMV-infected Cst7-/- mice exhibited more severe clinical disease associated with increased demyelination and impaired remyelination. The increase in disease severity was associated with elevated expression of T cell chemoattractant chemokines, concurrent with increased neuroinflammation. These findings support the idea that cystatin F influences expression of proinflammatory gene expression impacting neuroinflammation, T cell activation and/or glia cell responses ultimately impacting neuroinflammation and neurologic disease.

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection.

Feline infectious peritonitis (FIP) is a multisystemic, generally lethal immuno-inflammatory disease of domestic cats caused by an infection with a genetic variant of feline coronavirus, referred to as the FIP virus (FIPV). We leveraged data from four different antiviral clinical trials performed at the University of California, Davis. Collectively, a total of 60 client-owned domestic cats, each with a confirmed diagnosis of naturally occurring FIP, were treated with a variety of antiviral compounds. The tested therapies included the antiviral compounds GS-441524, remdesivir, molnupiravir and allogeneic feline mesenchymal stem/stroma cell transfusions. Four client-owned cats with FIP did not meet the inclusion criteria for the trials and were not treated with antiviral therapies; these cats were included in the data set as untreated FIP control cats. ELISA and Western blot assays were performed using feline serum/plasma or ascites effusions obtained from a subset of the FIP cats. Normalized tissue/effusion viral loads were determined in 34 cats by a quantitative RT-PCR of nucleic acids isolated from either effusions or abdominal lymph node tissue. Twenty-one cats were PCR "serotyped" (genotyped) and had the S1/S2 region of the coronaviral spike gene amplified, cloned and sequenced from effusions or abdominal lymph node tissue. In total, 3 untreated control cats and 14 (23.3%) of the 60 antiviral-treated cats died or were euthanized during (13) or after the completion of (1) antiviral treatment. Of these 17 cats, 13 had complete necropsies performed (10 cats treated with antivirals and 3 untreated control cats). We found that anticoronaviral serologic responses were persistent and robust throughout the treatment period, primarily the IgG isotype, and focused on the viral structural Nucleocapsid and Membrane proteins. Coronavirus serologic patterns were similar for the effusions and serum/plasma of cats with FIP and in cats entering remission or that died. Viral RNA was readily detectable in the majority of the cats in either abdominal lymph node tissue or ascites effusions, and all of the viral isolates were determined to be serotype I FIPV. Viral nucleic acids in cats treated with antiviral compounds became undetectable in ascites or abdominal lymph node tissue by 11 days post-treatment using a sensitive quantitative RT-PCR assay. The most common pathologic lesions identified in the necropsied cats were hepatitis, abdominal effusion (ascites), serositis, pancreatitis, lymphadenitis, icterus and perivasculitis. In cats treated with antiviral compounds, gross and histological lesions characteristic of FIP persisted for several weeks, while the viral antigen became progressively less detectable.

Studies have shown that the COVID-19 pandemic led to global panic and ultimately, an increase in antimicrobial resistance (AMR). Research has reported on the misuse of antimicrobials during theCOVID-19 outbreak, which led to global complications. The misuse of antimicrobials discussed in the literature includes the empirical use of antibiotics, the knowledge gaps, and the excessive use of disinfectant products. There has been a greater impact of the misuse of antimicrobials on developing countries due to their lack of resources which will result in improper sanitation, inadequate infrastructure, and limited preparedness for future pandemics. To combat the increase in AMR, it is necessary to explore a variety of resolutions. These resolutions may include antimicrobial stewardship programs, rapid diagnostic methods, and funding for communicative research. Collaborative efforts between clinicians and researchers can lead to future advancements in AMR. To inhibit the progression of AMR, it is important to further research and further exploration.

Coronavirus stands for a large family of viruses characterized by protruding spikes surrounding a lipidic membrane adorned with proteins. The present study explores the adhesion of transmissible gastroenteritis coronavirus (TGEV) particles on a variety of reference solid surfaces that emulate typical virus‐surface interactions. Atomic force microscopy informs about trapping effectivity and the shape of the virus envelope on each surface, revealing that the deformation of TGEV particles spans from 20% to 50% in diameter. Given this large deformation range, experimental Langmuir isotherms convey an unexpectedly moderate variation in the adsorption‐free energy, indicating a viral adhesion adaptability which goes beyond the membrane. The combination of an extended Helfrich theory and coarse‐grained simulations reveals that, in fact, the envelope and the spikes present complementary adsorption affinities. While strong membrane‐surface interaction lead to highly deformed TGEV particles, surfaces with strong spike attraction yield smaller deformations with similar or even larger adsorption‐free energies. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron entry involves spike (S) glycoprotein-mediated fusion of viral and late endosomal membranes. Here, using single-molecule Förster resonance energy transfer (sm-FRET) imaging and biochemical measurements, we directly visualized conformational changes of individual spike trimers on the surface of SARS-CoV-2 Omicron pseudovirions during fusion activation. We observed that the S2 domain of the Omicron spike is a dynamic fusion machine. S2 reversibly interchanges between the pre-fusion conformation and two previously undescribed intermediate conformations. Acidic pH shifts the conformational equilibrium of S2 toward an intermediate conformation and promotes the membrane hemi-fusion reaction. Moreover, we captured conformational reversibility in the S2 domain, which suggests that spike can protect itself from pre-triggering. Furthermore, we determined that Ca2+ directly promotes the S2 conformational change from an intermediate conformation to post-fusion conformation. In the presence of a target membrane, low pH and Ca2+ stimulate the irreversible transition to S2 post-fusion state and promote membrane fusion. [Display omitted] • Omicron spike fusion domain S2 shows dynamic plasticity • S2 spontaneously samples two functional intermediate conformations to fusion pathway • Low pH promotes formation of fusion competent intermediate conformations • Ca2+ catalyzes an S2 conformational change to a stable post fusion conformation at low pH Dey et al. used single molecule FRET for a real-time visualization of SARS-CoV-2 spike conformational dynamics on the virion surface during fusion triggered by low pH and Ca2+. The intermediates identified during dynamic S protein mediated fusion provide mechanistic insights for Omicron entry that may guide CoV inhibitor design. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusion The aim of the study was to assess changes in waist and hip circumference, as well as the waist‐to‐hip ratio (WHR) and waist‐to‐height ratio (WHtR) indices among adolescents (11–15‐year‐olds) from the Kraków during the COVID‐19 pandemic.Cross‐sectional studies were conducted in four main districts of the city in the years 2020 and 2022. The study group consisted of 1662 people. Measurements of height, waist circumference, and hip circumference were taken. The collected data were used to calculate the WHR and WHtR indices. Statistical analyses were performed using two‐way ANOVA and post hoc Tukey's test, as well as the Kruskal–Wallis test, depending on the normality of distribution.An increase in hip circumference was observed in most age groups of both sexes. Among 14–15‐year‐old boys, an increase in waist circumference was observed, while among girls, the majority of cohorts showed the opposite trend. Additionally, in most age groups, a decrease in the values of WHR and WHtR indices was observed in both sexes, except for boys aged 14–15.The study found that government‐imposed restrictions related to the COVID‐19 pandemic had an impact on waist circumference, hip circumference, WHR, and WHtR indicators among adolescents aged 11–15 from Kraków. While some results showed regression, suggesting potential factors such as reduced physical activity or increased screen time contributing to deteriorating outcomes. On the other hand, not all results changed, which may be attributed to the absence of modifications in dietary habits or physical activity as government restrictions ceased. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To learn about a project that aimed to support teams caring for children and young people to reflect on their experiences and the effects of the coronavirus disease 2019 (COVID-19) pandemic • To recognise the need to ensure staff are adequately prepared to manage any future surges in respiratory illness effectively • To be aware of the potential long-term effects of the COVID-19 pandemic on emotional health and well-being. The coronavirus disease 2019 (COVID-19) pandemic was a challenging experience for children and young people’s services, and the workforce. The Valuing All Staff Together programme was a one-year project hosted by the North West Paediatric Critical Care, Surgery in Children, Long Term Ventilation Operational Delivery Network to support teams caring for children and young people to reflect on their experiences of the COVID-19 pandemic. Using an online survey, focus groups and interviews, it gave staff the opportunity to explore and understand the effects of the pandemic and the subsequent surge in demand, including how these affected services and the emotional health and well-being of staff. This would enable better preparation for future surges in respiratory illness in terms of learning, training and development. This article describes the programme’s aim, method and findings, and the main recommendations for practice. [ABSTRACT FROM AUTHOR]

Background and Aims: The COVID‐19 pandemic significantly disrupted lower limb diabetes care. We aimed to map trends in diabetes‐related lower limb amputation and hospitalisation rates through the COVID‐19 pandemic. Methods: We performed a retrospective cohort study of all individuals who underwent a lower limb amputation for a diabetes‐related foot complication from 2018 to 2021 at the Royal Melbourne Hospital, a quaternary hospital in Australia. Hospitalisation rates with a diabetes‐related foot complication were collected for comparison. The start of the COVID‐19 epoch was defined as 16 March 2020, when a state of emergency was declared in Melbourne. Results: During the study period, 360 lower limb amputations for diabetes‐related foot complications were performed in 247 individuals. The median monthly number of amputations remained stable prior to and during the COVID‐19 epoch; there was a median of 8.0 amputations per month (interquartile range (IQR) = 6.5–11) before COVID‐19, compared to 6.5 amputations (IQR = 5.0–8.3) during the COVID‐19 epoch (P = 0.23). Hospitalisation with a diabetes‐related foot complication significantly increased from a median monthly rate of 11 individuals (IQR = 9.0–14) before COVID‐19 to 19 individuals (IQR = 14–22) during the COVID‐19 epoch (p < 0.001). Conclusions: Despite increased hospitalisations for diabetes‐related foot complications during COVID‐19, there was not a corresponding increase in amputation rates. Face‐to‐face care of diabetes‐related foot complications was prioritised at this centre and may have contributed to stable amputation rates during the pandemic. [ABSTRACT FROM AUTHOR]

In testing whether coronavirus defective viral genome 12.7 (DVG12.7) with transcription regulating sequence (TRS) can synthesize subgenomic mRNA (sgmRNA) in coronavirus-infected cells, it was unexpectedly found by Northern blot assay that not only sgmRNA (designated sgmDVG 12.7) but also an RNA fragment with a size less than sgmDVG 12.7 was identified. A subsequent study demonstrated that the identified RNA fragment (designated clvDVG) was a cleaved RNA product originating from DVG12.7, and the cleaved sites were located in the loop region of stem‒loop structure and after UU and UA dinucleotides. clvDVG was also identified in mock-infected HRT-18 cells transfected with DVG12.7 transcript, indicating that cellular endoribonuclease is responsible for the cleavage. In addition, the sequence and structure surrounding the cleavage sites can affect the cleavage efficiency of DVG12.7. The cleavage features are therefore consistent with the general criteria for RNA cleavage by cellular RNase L. Furthermore, both the cleavage of rRNA and the synthesis of clvDVG were also identified in A549 cells. Because (i) the cleavage sites occurred predominantly after single-stranded UA and UU dinucleotides, (ii) the sequence and structure surrounding the cleavage sites affected the cleavage efficiency, (iii) the cleavage of rRNA is an index of the activation of RNase L, and (iv) the cleavage of both rRNA and DVG12.7 was identified in A549 cells, the results together indicated that the preferential cleavage of DVG12.7 is correlated with cellular endoribonuclease with the characteristics of RNase L and such cleavage features have not been previously characterized in coronaviruses. [ABSTRACT FROM AUTHOR]

Coronavirus is a family of viruses that cause upper respiratory infections in humans. Drug properties can be obtained by studying the molecular structure of corresponding drugs. The calculation of the topological index of a drug structure enables scientists to have a better understanding of the physical chemistry and biological characteristics of drugs. In this paper, we study topological indices and find the exact formulas for general topological indices m S O γ (G) and K A (γ , η) 1 (G). By the appropriate choice of parameters γ and η, several new/old inequalities that reveal topological indices are obtained. [ABSTRACT FROM AUTHOR]

Over the course of the last year and a half, the Coronavirus has swept across the world causing death and devastation to our geriatric population residing in long term care facilities, also known as nursing homes. This paper explores the complicated grief responses exhibited by individuals who were affected by nursing home resident COVID-19 deaths. Nursing home resident survivors, families of the deceased residents, and healthcare workers in this situation have experienced a wide variety of complicated grief responses that need to be addressed. To address this need, an application will follow regarding the usage of a garden memorial ritual and ceremony to help these grievers in their first steps of mourning. [ABSTRACT FROM AUTHOR]

National Taiwan University Hospital (NTUH) has demonstrated exceptional resilience and adaptability in its response to the COVID-19 pandemic. Since the outbreak in early 2020, NTUH has been at the forefront of Taiwan's healthcare system, taking proactive measures to prepare for and manage the pandemic. The hospital swiftly established dedicated outpatient clinics and wards, which were crucial in isolating and treating COVID-19 patients. NTUH also played a pivotal role in assisting the government with the development of diagnostic reagents and vaccines and contributing to the global effort to combat the disease. To address the long-term effects of COVID-19, NTUH established a special clinic for integrated care in September 2021, offering physical, occupational, and speech therapy to help patients recover and return to normal life. NTUH also shared its pandemic prevention experience internationally, participating in video conferences to discuss its preventive measures and best practices. In caring for frontline healthcare workers, NTUH established interdisciplinary care teams to provide psychological support, assistance with basic daily needs, and effective social, psychological, and mental health support programs. In conclusion, NTUH demonstrated efficient response capabilities and care for healthcare workers during the COVID-19 pandemic, providing valuable insights for future challenges in dealing with emerging infectious diseases. [ABSTRACT FROM AUTHOR]

Purpose: To identify the prevalence and risk factors of coronavirus disease 2019 (COVID-19) reinfection in patients with rheumatoid arthritis (RA). Materials and Methods: This study retrospectively analyzed patients with RA with a documented COVID-19 infection between January 2021 and December 2022 at a tertiary hospital in Seoul, South Korea. Reinfection was defined as a subsequent positive test result for severe acute respiratory syndrome coronavirus 2 at least 3 months after the initial infection. Cox proportional hazards models with backward elimination were employed to assess the association between potential risk factors and risk of reinfection. Results: Of 351 included patients with RA {female, 81.5%; median age, 58.0 years [interquartile range (IQR), 48.0–66.0]}, 252 (71.8%) were treated with methotrexate and 12 (3.4%) received leflunomide during the initial infection. Over a median follow-up of 1.5 (IQR, 1.1–1.6) years, 43 (12.3%) patients experienced reinfection, equating to an incidence rate of 8.97 per 100 patient-years. The median time interval between infections was 0.8 (IQR, 0.6–1.2) years. Among the risk factors, leflunomide use showed a significant association with reinfection (hazard ratio, 2.968; 95% confidence interval, 1.057–8.335; p=0.039). However, no significant changes occurred in disease activity following reinfection [disease activity score using 28 joints: baseline median, 2.3 (IQR, 1.9– 2.8); post-reinfection median, 2.3 (IQR, 1.8–2.6), p for change=0.895]. Conclusion: In this retrospective cohort study of patients with RA with COVID-19 infection, approximately 12% of patients experienced reinfection without significant change in disease activity. Leflunomide use was associated with a higher risk of reinfection. [ABSTRACT FROM AUTHOR]

The COVID-19 epidemic has become a major international health emergency. Millions of people have died as a result of this phenomenon since it began. Has there been any successful pharmacological treatment for COVID-19 since the initial report on the virus? How many searches are undertaken to address the impact of the infection? What is the number of drugs that have undergone investigation? What are the mechanisms of action and adverse effects associated with the investigated pharmaceuticals used to treat COVID-19? Has the Food and Drug Administration (FDA) approved any medication to treat COVID-19? To date, our understanding is based on a restricted corpus of published investigations into the treatment of COVID-19. It is important to note that no single study comprehensively encompasses all pharmacological interventions for COVID-19. This paper provides an introductory summary of a bibliometric analysis conducted on the data about COVID-19, sourced explicitly from two platforms, namely PubMed and ScienceDirect. The analysis encompasses the period spanning from 2019 to 2022. Furthermore, this study examines the published literature about the pharmacological interventions for the novel coronavirus disease 2019 (COVID-19), explicitly focusing on the safety and effectiveness of different medications such as Remdesivir (marketed as Veklury®), Lopinavir/Ritonavir (commercially known as Kaletra® or Aluvia®), Ribavirin, Favipiravir (marketed as Avigan®), Ivermectin, Casirivimab and Imdevimab (branded as Ronapreve®), Sotrovimab (marketed as Xevudy®), Anakinra, Molnupiravir, Nirmatrelvir/Ritonavir (marketed as Paxlovid®), and Galidesivir. Findings indicate that while Remdesivir and Nirmatrelvir/Ritonavir show significant efficacy in reducing hospitalization and severe outcomes, drugs like Lopinavir/Ritonavir and Ivermectin have inconsistent results. Our insights suggest a multifaceted approach incorporating these therapies can significantly improve patient outcomes. Repurposing drugs has been critical in rapidly responding to COVID-19, allowing existing medications to be used in new ways to combat the virus. Combination therapies and further research are essential to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Hospitalized COVID-19 patients with troponin elevation have a higher prevalence of cardiac abnormalities than control individuals. However, the progression and impact of myocardial injury on COVID-19 survivors remain unclear. This study sought to evaluate myocardial injury in COVID-19 survivors with troponin elevation with baseline and follow-up imaging and to assess medium-term outcomes. This was a prospective, longitudinal cohort study in 25 United Kingdom centers (June 2020 to March 2021). Hospitalized COVID-19 patients with myocardial injury underwent cardiac magnetic resonance (CMR) scans within 28 days and 6 months postdischarge. Outcomes were tracked for 12 months, with quality of life surveys (EuroQol-5 Dimension and 36-Item Short Form surveys) taken at discharge and 6 months. Of 342 participants (median age: 61.3 years; 71.1% male) with baseline CMR, 338 had a 12-month follow-up, 235 had a 6-month CMR, and 215 has baseline and follow-up quality of life surveys. Of 338 participants, within 12 months, 1.2% died; 1.8% had new myocardial infarction, acute coronary syndrome, or coronary revascularization; 0.8% had new myopericarditis; and 3.3% had other cardiovascular events requiring hospitalization. At 6 months, there was a minor improvement in left ventricular ejection fraction (1.8% ± 1.0%; P < 0.001), stable right ventricular ejection fraction (0.4% ± 0.8%; P = 0.50), no change in myocardial scar pattern or volume (P = 0.26), and no imaging evidence of continued myocardial inflammation. All pericardial effusions (26 of 26) resolved, and most pneumonitis resolved (95 of 101). EuroQol-5 Dimension scores indicated an overall improvement in quality of life (P < 0.001). Myocardial injury in severe hospitalized COVID-19 survivors is nonprogressive. Medium-term outcomes show a low incidence of major adverse cardiovascular events and improved quality of life. (COVID-19 Effects on the Heart; ISRCTN58667920) [Display omitted] [ABSTRACT FROM AUTHOR]

State health departments' (SHD) role in infection prevention and control (IPC) includes robust educational and consultative services for various health care settings. During the COVID-19 pandemic, Washington-SHD (W-SHD) IPC staff conducted remote and on-site Infection Control Assessment and Response (ICAR) consultations for long-term care (LTC) and non-LTC health care facilities. ICAR consultations were classified as "reactive" in response to a COVID-19 outbreak or "proactive" to help facilities improve IPC protocols. Facility addresses were geocoded to census tracks, classifying urban or rural areas. Facility types and characteristics were analyzed, assessing the impacts of repeat visits. All descriptive statistics, Pearson's χ2 tests, and odds ratios were calculated. Between March 2020 and December 2022, W-SHD conducted 3,093 ICARs at 1,703 health care facilities in 94.9% (37/39) of Washington counties. Of the total visits, most were in LTC (90.5%) and 48.9% were reactive. Facilities with initial on-site ICARs had 1.5 times the odds of having a repeat visit than facilities with initial remote visit (95% CI: 1.21, 1.87). Maintaining strong connections with health care facilities can help bolster infection prevention practices and minimize loss of information at the facility level. Evidence-based findings on the sustainability of the W-SHD's ICAR services during the COVID-19 pandemic illustrated the value of public health IPC programs. • Public health infection control programs expanded during the COVID-19 pandemic. • From 2020 to 2022, 3,093 consultations were conducted at 1,703 health care facilities. • Facilities were more likely to have a repeat visit if they first had a reactive visit. • Facilities were more likely to have a repeat visit if they first had an on-site visit. • Public health infection control consultations build trust with health care facilities. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To read the findings of a study that explored patients’ and professionals’ experiences of virtual clinics during COVID-19 • To recognise the need to assess individual patients when considering the use of virtual clinics • To acknowledge the need for appropriate training and equipment for staff to enhance their experience of virtual clinics. Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in the rapid implementation of virtual clinics to conduct consultations via telephone or video to minimise contact between staff and patients. Aim: To investigate the experiences of patients with cancer and healthcare professionals of virtual clinics during COVID-19 and to explore ways to improve their experiences. Method: A qualitative study involving semi-structured interviews with 36 patients and ten healthcare professionals at a London NHS trust. Data were analysed using thematic analysis. Findings: Five themes emerged from analysis – acceptance, benefits, communication, technology and choice. Most participants were accepting of virtual clinics and supported their continuing use. The average satisfaction rating for virtual clinics was higher among patients than among healthcare professionals; many healthcare professionals suggested that support in setting up video-based virtual clinics might improve their satisfaction. Conclusion: Patients’ individual needs should be considered when deciding whether to use virtual or face-to-face clinics, while staff require appropriate training and adequate equipment to enhance their experience of virtual clinics. [ABSTRACT FROM AUTHOR]

BACKGROUND: In response to the COVID-19 pandemic, educational institutions had to swiftly adapt and transition to remote teaching in order to maintain academic activities. However, these changes presented a number of challenges for professors, which could have negative effects on their health. OBJECTIVE: To analyze the association between changes in dietary and sleep habits, physical activity level, and sedentary behavior with the development of non-communicable diseases (NCDs) among Brazilian higher education professors during the pandemic period. METHODS: This is a cross-sectional and retrospective study conducted using an online form. Generalized linear models, adjusted for age, sex, and body mass index, were used to verify the difference between pre-pandemic and pandemic periods. Logistic regression models were used to predict the odds ratio (OR) for the development of NCDs according to physical activity time, sedentary behavior time, dietary and sleep patterns. RESULTS: A total of 936 professors residing across Brazil participated in the survey. The duration of sedentary behavior increased, sleep duration slightly decreased, and meal times shifted to earlier during the pandemic. A total of 22.9%of the participants reported the diagnosis of some NCDs during this period. Physical activity practice was associated with a lower risk of diseases during the pandemic, regardless of the intensity performed. On the other hand, late eating habits and excessive food consumption during the pandemic were associated with a higher risk. CONCLUSION: The results provide data that can help in the development of public policies that promote health actions to minimize the consequences associated with the pandemic period. [ABSTRACT FROM AUTHOR]

Context Obesity is a risk factor for coronavirus disease 2019 (COVID-19)-related outcomes; however, the mechanism remains unclear. Objective The objective of this analysis was to determine whether inflammation mediates the association between obesity and COVID-19 outcomes. Methods The International Study of Inflammation in COVID-19 (ISIC): A Prospective Multi-Center Observational Study Examining the Role of Biomarkers of Inflammation in Predicting Covid-19 Related Outcomes in Hospitalized Patients, was conducted at 10 hospitals in the United States and Europe. Participants were adults hospitalized specifically for COVID-19 between February 1, 2020, through October 19, 2022. Inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), were measured at admission. Associations were examined between body mass index (BMI, kg/m2) and a composite of death, need for mechanical ventilation, and renal replacement therapy, stratified by pre- and post-Omicron variants. The contribution of inflammation to the relationship between obesity and outcomes was assessed. Results Among 4644 participants (mean age 59.3, 45.6% male, 21.8% BMI ≥ 35), those with BMI > 40 (n = 485) had 55% higher odds of the composite outcome (95% CI, 1.21-1.98) compared with nonobese individuals (BMI < 30, n = 2358) in multivariable analysis. In multiple mediation analysis, only suPAR remained a significant mediator between BMI and composite outcome. Associations were amplified for participants younger than 65 years and with pre-Omicron variants. Conclusion Obesity is associated with worse outcomes in COVID-19, notably in younger participants and in the pre-Omicron era. Inflammation, as measured by suPAR, is a significant mediator of the association between obesity and COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

The ongoing global pandemic of the coronavirus 2019 (COVID‐19) disease is caused by the virus SARS‐CoV‐2, with very few highly effective antiviral treatments currently available. The machinery responsible for the replication and transcription of viral RNA during infection is made up of several important proteins. Two of these are nsp12, the catalytic subunit of the viral polymerase, and nsp9, a cofactor of nsp12 involved in the capping and priming of viral RNA. While several recent studies have determined the structural details of the interaction of nsp9 with nsp12 in the context of RNA capping, very few biochemical or biophysical details are currently available. In this study, we have used a combination of surface plasmon resonance (SPR) experiments, size exclusion chromatography (SEC) experiments, and biochemical assays to identify specific nsp9 residues that are critical for nsp12 binding as well as RNAylation, both of which are essential for the RNA capping process. Our data indicate that nsp9 dimerization is unlikely to play a significant functional role in the virus. We confirm that a set of recently discovered antiviral peptides inhibit nsp9–nsp12 interaction by specifically binding to nsp9; however, we find that these peptides do not impact RNAylation. In summary, our results have important implications for future drug discovery efforts to combat SARS‐CoV‐2 and any newly emerging coronaviruses. [ABSTRACT FROM AUTHOR]

Background: A review of key learnings from the response to the COVID-19 pandemic in nursing homes in Ireland can inform planning for future pandemics. This study describes barriers and facilitators contributing to COVID-19 outbreak management from the perspective of frontline teams. Methods: A qualitative study involving ten online focus group meetings was conducted. Data was collected between April and June 2023. The focus group discussions explored the views, perceptions and experiences of COVID-19 Response Team (CRT) members, clinical/public health experts who worked with them, and care professionals who worked in frontline managerial roles during the pandemic. All nine Community Healthcare Organisations and six Public Health Areas in Ireland were represented. Inductive reflexive thematic analysis was carried out using NVivo Pro 20. Results: In total, 54 staff members participated in focus group meetings. Five themes were developed from a thematic analysis that covered topics related to (1) infection prevention and control challenges and response to the pandemic, (2) social model of care and the built environment of nursing homes, (3) nursing home staffing, (4) leadership and staff practices, and (5) support and guidance received during the pandemic. Conclusions: The response to the COVID-19 pandemic has resulted in a steep learning curve, internationally and in Ireland. Preparing better for future pandemics not only requires changes to infection control and outbreak response but also to the organisation and operation of nursing homes. There is a great need to strengthen the long-term care sector's regulations and support around staffing levels, nursing home facilities, governance, use of technology, infection prevention and control, contingency planning, and maintaining collaborative relationships and strategic leadership. Key findings and recommendations from the Irish example can be used to improve the quality of care and service delivery at local, national, and policy levels and improve preparedness for future pandemics, in Ireland and internationally. [ABSTRACT FROM AUTHOR]

Key points Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year. Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year. Recurrent viral infections pose a greater risk of chronic rhinosinusitis than single episodes. [ABSTRACT FROM AUTHOR]

A prominent characteristic of. COVID-19 is the long incubation period, the lack of symptoms during that period, and significant geographic variation in prevalence and testing. This article investigates the relationship between testing and infection based on an Israeli sample of 193 municipalities and a report from 11 May 2020. Results support an exponential rise in the fraction of positive. COVID-19 outcomes with the fraction of tests. Finally, under conditions of equal socioeconomic ranking, population density and income inequality, the projected efficiency of tests rises with population density and the Gini index and drops with socioeconomic ranking. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has had a well-evidenced impact on adolescents, who are especially sensitive to pandemic disruptions given the critical role of socialization in their development. In Chile too, evidence shows increases in mental health complaints among adolescents over the lockdown period. Our study aimed at exploring the experiences of Chilean adolescents regarding their mental health during the lockdown and school closure (March 2020-December 2021), and during the return to on-site education (2022) as informed by adolescents and school staff, with a focus on family, school, and social sources of risk and support for adolescents' wellbeing during these periods. Methods: Using a qualitative approach, we conducted semi-structured interviews with 19 adolescents and 16 staff members from schools in an urban area of Chile. Results: Through thematic analysis, we generated five themes: [1] Adolescents in a mental health crisis, comprising a range of distressing experiences and mental health problems. This crisis was fueled by alterations in the functioning of adolescents' systems: [2] Broken support systems (peers and school); [3] The school agenda must go on, reflecting schools' strict compliance with the educational curriculum; and [4] Blurred boundaries between home and school life and within the family. Finally [5], Development will (try to) find its way describes how most participants experienced a bouncing back to wellbeing in the course of the school year upon return, and how some developmental milestones took place despite the abnormal conditions, providing evidence for resilience amid pandemic adversity. Conclusions: The findings give insight into how the exchanges between the adolescent and the social systems they are embedded in were interfered. The results help us understand the challenges for mental health during and after the pandemic, and highlight adolescents' capacity to thrive as normality was restored. The results also underscore the importance of upholding stability across adolescents' systems and routines, in order to mitigate impacts on wellbeing amid abnormal circumstances. The findings are relevant for development-informed initiatives in policy design in the aftermath of the pandemic and in future crisis management responses. [ABSTRACT FROM AUTHOR]

Porcine hemagglutinating encephalomyelitis virus (PHEV) is the only known porcine neurotropic coronavirus, which is prevalent worldwide at present. It is of great significance to understand the genetic and evolutionary characteristics of PHEV in order to perform effective measures for prevention and control of this disease. In this study, a total of 6,986 tissue samples and nasopharyngeal swabs were collected from different regions of Guangxi province in southern China during 2021-2024, and were tested for PHEV using a quadruplex RT-qPCR. The positivity rate of PHEV was 2.81% (196/6,986), of which tissue samples and nasopharyngeal swabs had 2.05% (87/4,246) and 3.98% (109/2,740) positivity rates, respectively. Fifty PHEV positive samples were selected for PCR amplification and gene sequencing. Sequence analysis revealed that the nucleotide homology and amino acid similarities of S, M, and N genes were 94.3%-99.3% and 92.3%-99.2%, 95.0%-99.7% and 94.7%-100.0%, 94.0%-99.5% and 93.5%-99.3%, respectively, indicating M and N genes were more conservative than S gene. Phylogenetic trees based on these three genes revealed that PHEV strains from different countries could be divided into two groups G1 and G2, and the PHEV strains from Guangxi province obtained in this study distributed in subgroups G1c and G2b. Bayesian analysis revealed that the population size of PHEV has been in a relatively stable state since its discovery until it expanded sharply around 2015, and still on the slow rise thereafter. S gene sequences analysis indicated that PHEV strains existed variation of mutation, and recombination. The results indicated that the prevalent PHEV strains in Guangxi province had complex evolutionary trajectories and high genetic diversity. To the best of our knowledge, this is the first report on the genetic and evolutionary characteristics of PHEV in southern China. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic affected the health of millions of people, both directly through infection and indirectly through delayed diagnosis and treatment of non-COVID-19 illnesses. The aim of this study was to check the impact of the COVID-19 pandemic on the diagnosis and treatment of appendicitis in children. Methods: The study was carried out at the Department of Paediatric Surgery of the Marciniak Hospital (Wrocław, Poland) and covered two periods, the pre-pandemic one (P1, 01/03/2019–29/02/2020) and the pandemic one (P2, 01/03/2020–28/02/2021). Results: The number of admissions of patients with suspected appendicitis and observation-only patients decreased during the pandemic (400/289 and 226/160, respectively). Although the number of operated children was similar during both analyzed periods (P1: 174, P2: 160), the rate of surgical interventions was significantly higher during P2 (55.4%) than during P1 (43.5%) (χ2 test: p = 0.00272). The values of the variables quantifying disease progression and severity of inflammation, selected inflammation-related parameters detected by laboratory blood tests, latencies from the onset of symptoms to the admission and from the admission to the operation, and total duration of hospitalization did not differ significantly between the pre-pandemic and pandemic periods. Conclusions: These results show that the COVID-19 pandemic led to more rigorous and careful triage of pediatric patients suspected of acute appendicitis that did not have a negative impact on patient outcomes. [ABSTRACT FROM AUTHOR]

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639–1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633–1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5–15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis. [ABSTRACT FROM AUTHOR]

Background: In COVID-19 management, a variety of pharmaceutical interventions (PI) and non- pharmaceutical interventions (NPI) were adopted to limit the spread of the disease and its associated deaths. We aimed to evaluate the impact of PI and NPI on risks of COVID-19 transmission and deaths. Method: We collected aggregate data from March 2nd, 2020, to December 1, 2022 from the Tunisian Ministry of Health's website and OurWorldInData.org site. NPI Periods (NPIP: March 2020 to March 2021) and PI Periods (PIP) were distributed to NPIP1, 2, 3 and 4 and to PIP1, 2, 3 and 4, respectively. We calculated the Relative Risks (RR) and 95% Confidence Intervals (CI) by comparing the subsequent period with previous one. Results: The risk of SARS-CoV-2 transmission increased progressively from the zero cases period (NPIP2) to the mitigate strategy period (NPIP3) (RR = 14.0; 95% CI: 12.4–15.8) and to the stop-and-go epidemic control period (NPIP4) (RR = 23.1 (95% CI: 22.4–23.9). It was stabilized in the targeted vaccination period (PIP1) (RR = 1.08, 95% CI: 1.07–1.08) and reduced during the mass vaccination period (PIP2) (RR: 0.50, 95% CI: 0.50–0.51). SARS-CoV-2 transmission, increased during PIP3 concomitant with the Omicron wave (RR = 2.65, 95% CI: 2.64–2.67). It remained at a low level in PIP4 (RR = 0.18; 95% CI: 0.18–0.18). Compared to NPIP2, NPIP3 and NPIP4 were associated with a higher risk of COVID-19 mortality (RR = 3.337; 95% CI: 1.797–6.195) and (RR = 72.63 (95% CI: 54.01–97.68), respectively. Since the start of the immunization program, the risk of COVID-19 death has consistently decreased. In comparison to each previous period, the risk transitioned in PIP1 to RR = 0.91; 95% CI: 0.88–0.93, then to RR = 0.85; 95% CI: 0.83–0.88 in PIP2, to RR = 0.47; 95% CI: 0.45–0.50 in PIP3, and to RR = 0.19; 95% CI: 0.18–0.24 during PIP4. Conclusion: In terms of lowering the risk of transmission and mortality, the NP strategy at the beginning of the epidemic outperformed the IP strategy during the outbreak. [ABSTRACT FROM AUTHOR]

Prediction of protein fitness from computational modeling is an area of active research in rational protein design. Here, we investigated whether protein fluctuations computed from molecular dynamics simulations can be used to predict the expression levels of SARS‐CoV‐2 receptor binding domain (RBD) mutants determined in the deep mutational scanning experiment of Starr et al. [Science (New York, N.Y.) 2022, 377, 420] Specifically, we performed more than 0.7 milliseconds of molecular dynamics (MD) simulations of 557 mutant RBDs in triplicate to achieve statistical significance under various simulation conditions. Our results show modest but significant anticorrelation in the range [−0.4, −0.3] between expression and RBD protein flexibility. A simple linear regression machine learning model achieved correlation coefficients in the range [0.7, 0.8], thus outperforming MD‐based models, but required about 25 mutations at each residue position for training. [ABSTRACT FROM AUTHOR]

Background/objectives: Considering the diverse symptomatology of COVID-19—ranging from mild to severe cases—multi-professional interventions are crucial for enhancing physical recovery, nutritional status, and mental health outcomes in affected patients. Thus, this study aimed to investigate the effects of such an intervention on health-related physical fitness and biomarkers in overweight COVID-19 survivors with varying degrees of symptom severity after 8 weeks and 16 weeks. Methods: This non-randomized clinical trial included 59 overweight COVID-19 survivors (32 males and 27 females) divided into three groups: mild (n = 31), moderate (n = 13), and severe/critical (n = 15). The participants underwent a multi-professional program and were assessed for anthropometric and body composition (primary outcome), as well as physical fitness and biochemical markers (secondary outcome) 8 and 16 weeks before the intervention. Results: After 8 weeks, time effects were observed for the maximum isometric handgrip strength (p < 0.001), maximum isometric lumbar-traction strength (p = 0.01), flexibility (p < 0.001), abdominal strength–endurance (p < 0.001), the sit-and-stand test (p < 0.001), maximum oxygen consumption (p < 0.001), and distance covered in the 6 min walk test (p < 0.001). Additionally, time effects were also observed for fat mass (p = 0.03), body fat percentage (p = 0.02), abdominal circumference (p = 0.01), total cholesterol (p < 0.001), low-density lipoproteins (p < 0.001), and glycated hemoglobin (p < 0.001), with lower values after multi-professional interventions. After 16 weeks, the systolic and diastolic blood pressure showed significant reductions independently of the intervention group (p < 0.001). Conclusion: These findings suggest that multi-professional interventions can provide substantial benefits for post-COVID-19 patients, regardless of the severity of their initial symptoms. [ABSTRACT FROM AUTHOR]

ABSTRACT In April and May 2020, the United States banking industry approved over $650 billion in federal relief funds as part of the Paycheck Protection Program (PPP). Since then, extensive evidence of discriminatory lending has been revealed by investigative journalism and academic studies. Our study is based on 41 interviews with frontline banking professionals conducted during the days and weeks of the PPP rollout. We find that under the crisis conditions of the pandemic, capped funds in the PPP and built‐in incentives that encouraged certain types of loans, banking employees relied upon the professional norms and logic of the for‐profit sector. We argue that these norms and logics threatened the integrity of the PPP as a public relief programme by applying profit‐oriented priorities to resources marked for universal and fair distribution. Our findings offer new directions for theorising sector‐level differences in street‐level bureaucratic discretion in the context of mixed‐sector collaboration on public service delivery, particularly under conditions of crisis and urgency. [ABSTRACT FROM AUTHOR]

Background: COVID‐19 is a highly contagious virus that causes pneumonia, which quickly progresses to acute respiratory distress. In the case of COVID‐19, physiotherapy is critical in non‐invasive support management, postural changes, chest physiotherapy (CPT), and bed mobility. This study aims to look into the effects of physiotherapy intervention on functional outcome levels in COVID‐19 patients in the acute stage. Methods: A total of 60 severe COVID‐19 patients (54 males and 6 females) with a mean age of 50 years were studied. The intervention group (n = 30) had two daily physiotherapy sessions that included positioning, CPT, cardio exercises, breathing exercises, and early mobility, whereas the control group (n = 30) received only standard medical care. Patients were tested twice at the baseline and discharge using peripheral oxygen saturation, respiratory rate (RR) test, dyspnea rate, two‐min walk test, and spirometer scores, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). Results: The two groups improved significantly between the baseline and discharge ratings. The intervention group, on the other hand, significantly improved all outcome indicators at discharge (p‐value = 0.00). This study found that physiotherapy management improved oxygen saturation, RR, dyspnea, and lung function tests in COVID‐19 patients except in FVC (p‐value = 0.402) and FEV1(p‐value = 0.114). Conclusion: Physiotherapist interventions with COVID‐19 patients increase respiratory function and treatment time. [ABSTRACT FROM AUTHOR]