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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

We investigate the emergence, mutation profile, and dissemination of SARS-CoV-2 lineage B.1.214.2, first identified in Belgium in January 2021. This variant, featuring a 3-amino acid insertion in the spike protein similar to the Omicron variant, was speculated to enhance transmissibility or immune evasion. Initially detected in international travelers, it substantially transmitted in Central Africa, Belgium, Switzerland, and France, peaking in April 2021. Our travel-aware phylogeographic analysis, incorporating travel history, estimated the origin to the Republic of the Congo, with primary European entry through France and Belgium, and multiple smaller introductions during the epidemic. We correlate its spread with human travel patterns and air passenger data. Further, upon reviewing national reports of SARS-CoV-2 outbreaks in Belgian nursing homes, we found this strain caused moderately severe outcomes (8.7% case fatality ratio). A distinct nasopharyngeal immune response was observed in elderly patients, characterized by 80% unique signatures, higher B- and T-cell activation, increased type I IFN signaling, and reduced NK, Th17, and complement system activation, compared to similar outbreaks. This unique immune response may explain the variants epidemiological behavior and underscores the need for nasal vaccine strategies against emerging variants.

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]

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1-4. Despite the clinical evidence1,5-7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8-10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.

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.

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]

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.

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the Interferon paradox previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.

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.

Despite the unique advantages of IgG3 over other IgG subclasses, such as mediating enhanced effector functions and increased flexibility in antigen binding due to a long hinge region, the therapeutic potential of IgG3 remains largely unexplored. This may be attributed to difficulties in recombinant expression and the reduced plasma half-life of most IgG3 allotypes. Here, we report plant expression of two SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding. P5C3 and H4-IgG1 mAbs were subclass-switched to IgG3 formats, designed for efficient production and increased PK values, carrying three allotypic variations, referred to as -WT, -H, and -KVH. A total of eight mAbs were produced in glycoengineered plants that synthesize fucose-free complex N-glycans with great homogeneity. Antigen, IgG-FcγR immune complex and complement binding studies demonstrated similar activities of all mAbs. In accordance, P5C3 Abs showed minor alterations in SARS-CoV-2 neutralization (NT) and antibody-dependent cell-mediated virus inhibition (ADCVI). Clear functional differences were observed between H4 variants with superior ADCVI and NT potencies of H4 IgG3 H. Our comparative study demonstrates the production of an IgG3 variant carrying an Fc domain with equivalent or enhanced functions compared to IgG3-WT, but with the stability and PK values ​​of IgG1. Our data also demonstrate that both allotypic variability and antibody specificity are important for fine-tuning of activities, an important information for the development of future therapeutics.

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.

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Objective: The study aims to capture the emotional challenges faced by international students due to the changes in U.S. visa regulations during the COVID-19 outbreak. Participants: 165 international students from University of Florida participated in the study. Methods: We conducted a cross-sectional online survey using previously validated questionnaire tools (PHQ-9 and GAD-7). The collected data was quantitatively analyzed through different statistical approaches, including ANOVA, Independent Sample t-Test, and Binary Logistic Regression. Results: 18.8% of our study sample had a moderately severe to severe depressive status, and 20.6% of the study sample had severe anxiety. Additionally, there was a statistically significant difference in the depression and anxiety scores based on gender. Conclusions: Our findings addressed the importance of taking serious measures when emotionally impactful political issues arise to prevent the development of mental illnesses among international students at U.S. institutions of higher education. [ABSTRACT FROM AUTHOR]

Summary: Sleep is fundamental to health. The aim of this study was to analyse and determine factors predicting sleep quality during and after national lockdowns due to severe acute respiratory syndrome coronavirus 2 (COVID‐19) in the UK. A longitudinal online survey‐based study (SleepQuest) involving UK adults was administered in Spring 2020, Winter 2020, and Winter 2022 including questionnaires probing sleep quality, depression, anxiety, beliefs about sleep, demographics, COVID‐19 status, and exercise. The primary outcome was sleep quality (Pittsburgh Sleep Quality Index). A linear mixed‐effects model evaluated factors associated with baseline and longitudinal sleep quality. Complete data were provided by 3306 participants in Spring 2020, 2196 participants in Winter 2020, and 1193 in Winter 2022. Participants were mostly female (73.8%), white (97.4%), and aged over 50 years (81.0%). On average, participants reported poor sleep quality in Spring 2020 (mean [SD] Pittsburgh Sleep Quality Index score = 6.59 [3.6]) and Winter 2020 (mean [SD] Pittsburgh Sleep Quality Index score = 6.44 [3.6]), with improved but still poor sleep quality in Winter 2022 (mean [SD] Pittsburgh Sleep Quality Index score = 6.17 [3.5]). Improved sleep quality was driven by better subjective sleep and reduced daytime dysfunction and sleep latency. Being female, older, having caring responsibilities, working nightshifts, and reporting higher levels of depression, anxiety, and unhelpful beliefs about sleep were associated with worse baseline PSQI scores. Better sleep quality was associated with more days exercising per week at baseline. Interventions focusing on improving mental health, exercise, and attitudes towards sleep, particularly in at‐risk groups, may improve sleep‐related outcomes in future pandemics. [ABSTRACT FROM AUTHOR]

Objective: When COVID-19 was declared a pandemic there was concern that people living with asthma were at high-risk of poor outcomes. We aimed to explore the psychological impact of living with asthma in the United Kingdom during the pandemic. Methods and measures: Our mixed methods study, co-designed with patient and public involvement colleagues, included an online survey to detect anxiety/depression/post-traumatic stress disorder (PTSD) and health beliefs; and qualitative interviews. We recruited 849 participants for the survey and interviewed 26 between May and June 2020. Audio-recorded interviews were transcribed verbatim, and analysed thematically. Results: The survey identified that 77% of respondents were experiencing symptoms of anxiety, 77% were experiencing symptoms of depression, and PTSD was of concern for 61%. Two-thirds of respondents felt the pandemic had changed how they managed their asthma (n = 568, 66.9%), and over half felt that they had not been given adequate health information about COVID-19 (n = 495, 58.3%). Qualitative interviews identified five themes (1) health communication, (2) interaction with healthcare, (3) COVID-19-related concerns, (4) impact on mental health, and (5) behaviour change. Conclusion: Psychological distress was prevalent in people with asthma during the early stage of the pandemic. Understanding this may be useful to inform future healthcare/policy planning. [ABSTRACT FROM AUTHOR]

Children have a right to play, as outlined by the United Nations, due to its important role in holistic development. However, as with many other human rights, children's access to their right to play was disrupted by the COVID-19 pandemic and associated restrictions. With several studies demonstrating the ways in which children's play changed during times of restriction, this research aimed to explore whether these changes continued to be observed once restrictions had lifted. A mixed methods design was utilised: a 22-item questionnaire was distributed by schools in England to 124 caregivers who shared their observations of their children's play during times of restriction and the six months prior to data collection. Quantitative analysis demonstrates that increases in time to play, adult-child play, and outdoor play during the pandemic had been counteracted since restrictions were lifted; however, device play remained elevated. Qualitative comments highlight the impact of children's affect on their play, the activities children chose to pursue, and the extent of increases in screen time. The implications of these findings are discussed, including a need to place greater value on play in the home and the role of educational psychologists in supporting this. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the impact of the coronavirus pandemic on gynecology surgical training. Methods: A national cross‐sectional online survey was distributed to all trainees and trainers in the higher specialist training program for obstetrics and gynecology in Ireland. The survey consisted of questions on topics which included: the volume of surgical procedures performed before and since the pandemic, confidence in performing various gynecologic procedures before and since the pandemic and questions regarding the impact of the pandemic on wellbeing and work practices. Results: Trainers and trainees experienced a significant reduction in operative volumes for most procedure types. Analysis showed a significant reduction in the number of minor procedures performed by trainees (z = −2.7, P = 0.007) and a significant reduction in the number of all procedure types performed by trainers (minor procedures z = −3.78, P = <0.001; intermediate procedures z = −4.48, P = < 0.001; major procedures z = −3.69, P = < 0.001). Respondents reported they had less time for research and audit, were less able to attend courses or conferences and worried about the impact of their work on their families. Conclusions: In conclusion, this study has highlighted the current difficulties facing surgical trainees in gynecology because of the COVID‐19 pandemic. These challenges have compounded an already challenging training environment for gynecology trainees. Efforts must be made to continue to provide high‐quality tailored training to ensure the development of the next generation of gynecologic surgeons. Synopsis: A national survey which shows significant challenges with training in gynecology during the coronavirus pandemic. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 virus, which caused the COVID-19 pandemic, emerged in late 2019, leading to significant global health challenges due to the lack of targeted treatments and the need for rapid diagnosis. Aim/objective: This study aims to develop an AI-based system to accurately detect COVID-19 from CT scans, enhancing the diagnostic process. Methodology: We employ a faster region-based convolutional neural network (faster R-CNN) for extracting features from pre-processed CT images and use the chaotic satin bowerbird optimization algorithm (CSBOA) for fine-tuning the model parameters. Results: Our experimental results show high performance in terms of precision, recall, accuracy, and f-measure, effectively identifying COVID-19 affected areas in CT images. The suggested model attained 91.78% F1-score, 91.37% accuracy, 91.87% precision, and 90.3% recall with a learning rate of 0.0001. Conclusion: This method contributes to the advancement of AI-driven diagnostic tools, providing a pathway for improved early detection and treatment strategies for COVID-19, thus aiding in better clinical management. [ABSTRACT FROM AUTHOR]

Purpose: College students are potentially more vulnerable to stress and psychological distress, particularly during the pandemic. The aim of this study was to determine the occurrence of common mental disorders (CMD) and assess physical activity levels of college students during COVID-19 pandemic. We compared physical activity levels between students with and without CMD. Methods: Two hundred and fifty-six students aged 18–58 years participated in this study. The participants completed the Self-Report Questionnaire-20 and the International Physical Activity Questionnaire short form, for CMD and physical activity levels, respectively. Results: We observed 56.6% of students had CMD, which was significantly higher in women (63.8%). Most students were sedentary (43%). Moreover, those with CMD showed significantly high sedentary behavior, and low frequency and intensity in walking and vigorous physical activities. Conclusions: Implications imposed by COVID-19 pandemic and remote teaching possibly influenced these findings, increasing CMD symptoms and decreasing physical activity levels in college students. Thus, more studies are needed to understand the impacts of COVID-19 pandemic and remote teaching in this population. [ABSTRACT FROM AUTHOR]

Aim: To gain a better understanding of consumer experiences with and preferences for telephone and videoconference consultations (telehealth), and how these compare to traditional in-person consultations. Methods: A national cross-sectional survey was administered to a representative sample of Australian adults who have received a telehealth service within the last year. Consumers were recruited by Qualtrics® through their online sampling service. The sample was representative of the broader Australian population according to gender, age, location (state/territory), and place of residence (urban or remote). Information on demographics (e.g., age, gender, employment status), recent telehealth experience, and preferences for consultation modality was collected. To measure preferences consumers were asked to indicate which modality they would prefer (in-person, telephone, or videoconference) for different scenarios. These included consultations of various time lengths, and for the top ten conditions for which individuals sought a general practitioner. Results: A total of 1069 consumers completed the survey. When consumers were asked to describe their most recent telehealth appointment, most were for follow-up appointments (67%) and completed by telephone (77%) rather than by videoconference, and with a general practitioner (75%). In-person consultations at a clinic were the top preference in all clinical scenarios presented, except when needing a prescription or to receive test results. In these cases, a telephone consultation was the preferred modality. Inexperience with videoconference and duration of consultation influenced preference for consultation mode. Consumers preferred to have short consultations of around five minutes done by telehealth (telephone or videoconference), while they preferred in-person for longer consultations (up to 60 minutes). Conclusions: Many Australians have used telehealth in the past year to access healthcare, with telephone being the most common form of communication. Given the option and the experience to date, consumers prefer telephone when consultations related to either prescriptions or test results. Experience with videoconference for consultations increased consumer preferences for using it for future consultations. [ABSTRACT FROM AUTHOR]

During the early days of the COVID-19 pandemic, popular narratives of a 'resurgent nature' and portrayals of the virus as a form of 'revenge' prompted geographical reflection on the promises and limitations of ecological perspectives on the SARS-CoV-2 virus. Revisiting these reflections in the light of what we have learned from the pandemic, this article asks what is to be gained by attempting to think critically with the virus about human space as multispecies composition. Thinking ecologically with the virus can become a method for critically reconsidering naturalised and dualistic orders of exclusion and inclusion, health and unhealth, or belonging and unbelonging. Specifically, we focus in this article on the overlap of immunological and trans-antagonistic discourses with viral imaginaries of the pandemic, exploring the paradox of vulnerability that arises at this point of intersection. COVID-19 simultaneously highlights humans' mutual vulnerability as a horizontalising force and amplifies differential social vulnerabilities. In examining this paradox of vulnerability as it relates to viral discursive constructions of transness, we explore tensions between different modes of engaging, identifying and thinking with the virus in recognition that the social and the ecological cannot properly be considered as separate domains. The aim is not simply to propose an extended epidemiology that takes into account the complex human–nonhuman entanglement, but to explore the social, cultural and political implications of pandemic vulnerabilities and of thinking ecologically with the virus. We trace the shared conceptual underpinnings of ecological and immunological thought, showing that these same conceptual lineages manifest in political responses to the COVID-19 pandemic and exploring how they are expressed in queer- and trans-antagonistic discourse and policy. Building on these analyses, we develop a proposal for 'transing' the virus and a model for 'thinking ecologically' that is simultaneously liberatory, messy and agnostic. [ABSTRACT FROM AUTHOR]

Studies of the credibility of sources is a key research focus in the communication field, especially in journalism. Given the increase in misinformation as a consequence of the COVID-19 pandemic, source credibility is crucial for people to contrast news stories in an infodemic context. Our research, based on a demographic study (N = 2007) carried out in Spain during the COVID-19 pandemic, used a multifactor news credibility indicator to explore how different types of sources affected the perceived credibility of a fake news item on COVID-19 in the written digital press format. We also performed a cluster analysis to determine the subgroups profiled according to key sociodemographic variables (age, gender, and education). Our results indicate that expert and political sources had a null effect on news credibility, while citizen and celebrity sources had a clear negative effect. Furthermore, our fake news story that did not cite sources was awarded a positive level of credibility. We also found that age, gender, and education level were statistically significant in their association with news credibility. [ABSTRACT FROM AUTHOR]

It is often of primary interest to analyze and forecast the levels of a continuous phenomenon as a categorical variable. In this paper, we propose a new spatio-temporal model to deal with this problem in a binary setting, with an interesting application related to the COVID-19 pandemic, a phenomena that depends on both spatial proximity and temporal auto-correlation. Our model is defined through a hierarchical structure for the latent variable, which corresponds to the probit-link function. The mean of the latent variable in the proposed model is designed to capture the trend and the seasonal pattern as well as the lagged effects of relevant regressors. The covariance structure of the model is defined as an additive combination of a zero-mean spatio-temporally correlated process and a white noise process. The parameters associated with the space-time process enable us to analyze the effect of proximity of two points with respect to space or time and its influence on the overall process. For estimation and prediction, we adopt a complete Bayesian framework along with suitable prior specifications and utilize the concepts of Gibbs sampling. Using the county-level data from the state of New York, we show that the proposed methodology provides superior performance than benchmark techniques. We also use our model to devise a novel mechanism for predictive clustering which can be leveraged to develop localized policies. [ABSTRACT FROM AUTHOR]

Evidence of exposure to the pandemic SARS-CoV-2 has been described in numerous animal species, including pets, which are predisposed to coming into contact with this virus due to their close relationship with owners. It has been accepted that dogs are poorly susceptible to this virus and that seroconversion, rather than shedding, occurs following infection, which can occur directly through contact with infected owners or indirectly through environmental contamination. In this study, the seroprevalence of SARS-CoV-2 was evaluated in apparently health hunting and stray dogs of Campania region, southern Italy (sampled in September 2023). A total of 5/112 (4.5%) animals tested seropositive using two different commercial ELISAs. Stray animals had greater exposure than hunting dogs. The feces and blood of each animal were tested with a real-time PCR targeting the nucleocapsid and ORF1ab coding sequences. No animal tested positive in molecular investigations, indicating a past exposure without active infection at the time of sampling. [ABSTRACT FROM AUTHOR]

Background Objective Animals Methods Results Conclusion Although most cats with feline infectious peritonitis (FIP) respond to treatment with remdesivir or GS‐441524 or both with uneventful clinical courses, some die despite treatment.Identify predictive factors associated with short‐term mortality in cats with FIP treated with IV remdesivir or PO GS‐441524 or both.A total of 108 client‐owned cats with FIP.Retrospective multicenter study using data collected from medical records. Factors associated with short‐term mortality, defined as death within 84 days, were identified. Univariate analysis a t‐test, Mann‐Whitney U test, or Fisher's exact test and multivariate logistic regression were performed to assess patient characteristics and clinicopathological variables between survivors and nonsurvivors.The short‐term mortality rate was 12.0% (95% confidence interval [CI], 6.6%‐19.7%). Univariate analysis identified plasma lactate dehydrogenase activity (LDH; P < .001) and bilirubin concentration (P = .001) as being significantly increased in nonsurvivors, whereas concentrations of albumin (P = .003), total protein (P = .03), sodium (P = .005), and potassium (P = .005) were significantly lower. Additionally, nonsurvivors were significantly less likely to be febrile (≥39.4°C; P = .006). Of these variables, only plasma LDH activity ≥323 U/L, a cut‐point determined by receiver operating characteristic curve analysis, was significantly associated with short‐term mortality by multivariate analysis (odds ratio, 15.30; 95% CI, 1.18‐198.00; P = .04).Increased plasma LDH activity might be useful for predicting short‐term mortality, guiding monitoring, and establishing prognosis in cats with FIP. [ABSTRACT FROM AUTHOR]

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, Sunda pangolins (Manis javanica) involved in the illegal wildlife trade in mainland China were identified as hosts of severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Although it is unconfirmed whether pangolins or other traded wildlife served as intermediate hosts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the trafficking of pangolins presents a clear risk for transmission of viruses with zoonotic and epizootic potential regardless. We have investigated the origins of pangolin carcasses seized in Hong Kong and have evaluated their potential exposure to SARSr-CoVs, other coronaviruses, and paramyxoviruses, aiming to address a gap in our knowledge with regard to the role of wildlife trade in the maintenance and emergence of pathogens with zoonotic and epizootic potential. Results: Using a combination of virological and wildlife forensics tools, we investigated 89 Sunda pangolin carcasses seized by Hong Kong authorities during anti-smuggling operations in the territory conducted in 2013 (n = 1) and 2018 (n = 88). Swabs, organ tissues, blood, and other body fluids were collected during post-mortem examination. Two enzyme-linked immunosorbent assays (ELISAs), which employ a double-antigen sandwich format, were used to detect antibodies reactive against SARSr-CoVs. One individual was found to be seropositive with support from both methods, while five individuals exhibited a putatively seropositive result from one ELISA method. Polymerase chain reaction (PCR) screening for coronavirus and paramyxovirus ribonucleic acid (RNA) did not yield any positives. Based on genomic data, the seropositive individual was determined to have likely originated from Java, while the putatively seropositive individuals were determined to have originated from populations in Borneo, Java, and Singapore/Sumatra. Conclusions: While the role of pangolins in the evolution and ecology of SARS-CoV-2 is uncertain, our results suggest susceptibility and potential exposure of pangolins to SARSr-CoVs, occurring naturally or associated with the illegal trafficking of these animals. Complex dynamics between natural populations, traded individuals, and pathogen susceptibility complicate conclusions about the role of pangolins, as well as other host species, in the ecology of SARSr-CoVs and potentially zoonotic viruses with risk of future emergence. [ABSTRACT FROM AUTHOR]

Coronavirus 3C‐like protease (CoV 3CLpro) is essential for viral replication, providing an attractive target for monitoring the evolution of CoV and developing anti‐CoV drugs. Here, the substrate‐binding modes of 3CLpros from four CoV genera are analyzed and found that the S2 pocket in 3CLpro is highly conserved within each genus but differs between genera. Functionally, the S2 pocket, in conjunction with S4 and S1′ pockets, governs the genus‐specific substrate selectivity of 3CLpro. Resurrected ancestral 3CLpros from four CoV genera validate the genus‐specific divergence of S2 pocket. Drawing upon the genus‐specific S2 pocket as evolutionary marker, eight newly identified 3CLpros uncover the ancestral state of modern 3CLpro and elucidate the possible evolutionary process for CoV. It is also demonstrated that the S2 pocket is highly correlated with the genus‐specific inhibitory potency of PF‐07321332 (an FDA‐approved drug against COVID‐19) on different CoV 3CLpros. This study on 3CLpro provides novel insights to inform evolutionary mechanisms for CoV and develop genera‐specific or broad‐spectrum drugs against CoVs. [ABSTRACT FROM AUTHOR]

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]

The zoonotic transmission of influenza A viruses (IAVs) and coronaviruses (CoVs) may result in severe disease. Cleavage of the surface glycoproteins hemagglutinin (HA) and spike protein (S), respectively, is essential for viral infectivity. The transmembrane serine protease 2 (TMPRSS2) is crucial for cleaving IAV HAs containing monobasic cleavage sites and severe acute respiratory syndrome (SARS)-CoV-2 S in human airway cells. Here, we analysed and compared the TMPRSS2-dependency of SARS-CoV, Middle East respiratory syndrome (MERS)-CoV, the 1918 pandemic H1N1 IAV and IAV H12, H13 and H17 subtypes in human airway cells. We used the peptide-conjugated morpholino oligomer (PPMO) T-ex5 to knockdown the expression of active TMPRSS2 and determine the impact on virus activation and replication in Calu-3 cells. The activation of H1N1/1918 and H13 relied on TMPRSS2, whereas recombinant IAVs carrying H12 or H17 were not affected by TMPRSS2 knockdown. MERS-CoV replication was strongly suppressed in T-ex5 treated cells, while SARS-CoV was less dependent on TMPRSS2. Our data underline the importance of TMPRSS2 for certain (potentially) pandemic respiratory viruses, including H1N1/1918 and MERS-CoV, in human airways, further suggesting a promising drug target. However, our findings also highlight that IAVs and CoVs differ in TMPRSS2 dependency and that other proteases are involved in virus activation. [ABSTRACT FROM AUTHOR]

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with hypercoagulability and increased incidence of thrombotic events. In this study, we investigated the levels of neutrophil extracellular trap biomarkers and von Willebrand factor to assess if these could predict the occurrence of a thrombotic event in COVID-19 patients. We enrolled 202 patients hospitalized with symptomatic COVID-19 infection. Of those, 104 patients did not experience any type of thrombotic events before or during their hospitalization. These patients were compared to the other cohort of 98, who experienced thrombotic events before or during their hospitalization. In total, 61 patients who experienced thrombotic events had the event after initial blood collection, so the predictive capacity of biomarkers in these patients was evaluated. Citrullinated histone H3 was the best predictive biomarker for thrombotic events in COVID-19 regardless of age, sex, and race; disease severity was also a significant predictor in most thrombotic event groups. These results may better inform treatment and prophylaxis of thrombotic events in COVID-19 and similar viral illnesses in the future to improve outcomes and reduce mortality. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: Coronavirus was first officially reported in Wuhan city of China in December 2019. As this novel coronavirus spread rapidly throughout the world, health care workers faced many difficulties addressing the pandemic. In the present study, we explored the challenges faced by front-line health managers on human resource management, execution of the central policies, and training and in formulating innovative approaches during the coronavirus disease 2019 (COVID-19) pandemic in India. Methods: A qualitative study was conducted using framework analysis among front-line health managers concerning COVID-19 management at the district level. We conducted 120 in-depth interviews among eight states with the use of an interview guide. Results: The results are described under five sections: 'challenges of front-line managers in policymaking and its execution', 'human resource management', 'gaps in local execution of central policies', 'challenges in training workforce and data management', and 'innovative approaches adopted during COVID 19'. Conclusions: We observed that a centre-down approach was not appreciated much. Many participants felt that there was a need to understand the local context and appropriate amendment. The private system is a part of the Indian health system and can never be ignored; thus, all guidelines should include the private system. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to provide a population-based evaluation of vaccination coverage to prevent respiratory complications from SARS-COV-2, influenza, and pneumococcus, among communitydwelling persons with spinal cord injury/disease. Design: This is a cross-sectional survey conducted in 2022, utilizing questionnaires administered to persons with spinal cord injury/disease living in Switzerland. Main outcomes were ever-vaccination rates for SARS-COV-2, influenza, and pneumococcus. Secondary outcomes included demographics, lesion and education levels, as well as respiratory and cardiovascular conditions. Vaccine hesitancy was additionally assessed for all three vaccines in nonvaccinated persons through questions on reasons for not getting vaccinated. Results: A total of 1158 persons participated in this survey. Overall vaccination rates were highest for SARS-COV-2 86.5% (95% CI = 84.4-88.3), followed by influenza 44.6 (41.7-47.6) and pneumococcus: 7.5% (6.0-9.3). The most prominent reasons for not being vaccinated were doubt on effectiveness (72.7%) and potential side effects (60%) for SARS-COV-2, patients did not feel at risk for influenza (57%) and insufficient information from the physician (52.4%) for pneumococcus vaccination. Conclusions: In individuals with spinal cord injury/disease, vaccination coverage is notably low for influenza and especially pneumococcus. Vaccine hesitancy varies between vaccination types and is associated with vaccine-specific reasons. These findings underscore the imperative for updated clinical vaccination guidelines, improved public health information, and targeted intervention programs for specific patient groups. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines were released en masse globally in 2021 and were regarded by policy makers as crucial in dealing with the coronavirus pandemic. An important question is thus to understand the benefits of the vaccines beyond the direct effects of reducing mortality and morbidity. Using available epidemiological evidence on the effectiveness of vaccines we estimate the economic benefits of vaccination in five important Asian economies – India, Indonesia, South Korea, the Philippines and Vietnam – by applying a dynamic multi-country general equilibrium model. This framework captures the direct and indirect effects of vaccination. Our results show net benefits in terms of GDP for all five economies ranging from 0.16% (India) to 1.1% (South Korea); these depend on the degree of vaccination amongst the population. South Korea shows the most significant benefits while other countries experience smaller benefits. Our findings are consistent with other studies estimating the economic benefits of vaccination. [ABSTRACT FROM AUTHOR]