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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.

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.

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.

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]

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]

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]

Introduction: The expansion of telehealth during the COVID-19 pandemic may widen digital divides. It is essential to better understand the use of telehealth by the elderly population for the development of equitable telehealth tools. Objectives: This study aimed to describe the socioeconomic, clinical, and functional characteristics of elderly patients who were supported by a COVID-19 telehealth program. It also investigated the characteristics associated with the need for support for teleconsultations, hospitalization, and mortality. Methods: >Elderly patients supported by the TeleCOVID-MG program, between June 2020 and December 2021, in two Brazilian municipalities (Divinópolis and Teófilo Otoni) were included. Data were collected from electronic records and through phone call interviews. Descriptive and multivariable analyses were performed. Results: Among the 237 patients,121 were women (51.1%), mean age was 70.8 years (±8.5), 121 (51.1%) had less than 4 years of formal education, 123 patients (51.9%) had two or more comorbidities, and 68 (29%) reported functional decline in activities of daily life. Age greater than 80 years (odds ratio [OR]:4.68, 95% confidence interval [CI] 1.93–11.37, p = 0.001), lower educational level (OR:3.85, 95% CI 1.8–8.21, p < 0.001), hearing (OR:5.46, 95% CI: 1.24–11.27, p = 0.019), and visual (OR:15.10, 95% CI: 3.21–71.04, p = 0.001) impairments were characteristics associated with the need for support for teleconsultations. The need for support was associated with hospitalization and mortality (OR:5.08, 95% CI: 2.35–10.98, p < 0.001). Conclusion: Older age, lower educational level, and sensory impairments may compromise the effectiveness and the safety of the telehealth assistance to the elderly population. Functional evaluation and frailty screening should be considered part of the telehealth assessment of elderly patients. [ABSTRACT FROM AUTHOR]

The design and synthesis of antiviral compounds were guided by computationally predicted data against highly conserved non-structural proteins (Nsps) of the SARS-CoV-2 coronavirus. Chromenephenylmethanone-1 (CPM-1), a novel biphenylpyran (BPP), was selected from a unique natural product library based on in silico docking scores to coronavirus Nsps with high specificity to the methyltransferase protein (2′-O-MTase, Nsp10–16), which is responsible for viral mRNA maturation and host innate immune response evasion. To target the 2′-O-MTase, CPM-1, along with intermediate BPP regioisomers, tetrahydrophenylmethanones (TPMs), were synthesized and structurally validated via nuclear magnetic resonance (NMR) data and DP4+ structure probability analyses. To investigate the activity of these BPPs, the following in vitro assays were conducted: SARS-CoV-2 inhibition, biochemical target validation, mutagenicity, and cytotoxicity. CPM-1 possessed notable activity against SARS-CoV-2 with 98.9% inhibition at 10 µM and an EC50 of 7.65 µM, as well as inhibition of SARS-CoV-2's 2′-O-MTase (expressed and purified) with an IC50 of 1.5 ± 0.2 µM. In addition, CPM-1 revealed no cytotoxicity (CC50 of >100 µM) or mutagenicity (no frameshift or base-pair mutations). This study demonstrates the potential of computational modeling for the discovery of natural product prototypes followed by the design and synthesis of drug leads to inhibit the SARS-CoV-2 2′-O-MTase. [ABSTRACT FROM AUTHOR]

The development of novel tools to tackle viral processes has become a central focus in global health, during the COVID-19 pandemic. The spike protein is currently one of the main SARS-CoV-2 targets, owing to its key roles in infectivity and virion formation. In this context, exploring innovative strategies to block the activity of essential factors of SARS-CoV-2, such as spike proteins, will strengthen the capacity to respond to current and future threats. In the present work, we developed and tested novel bispecific molecules that encompass: (i) oligonucleotide aptamers S901 and S702, which bind to the spike protein through its S1 domain, and (ii) hydrophobic tags, such as adamantane and tert-butyl-carbamate-based ligands. Hydrophobic tags have the capacity to trigger the degradation of targets recruited in the context of a proteolytic chimera by activating quality control pathways. We observed that S901-adamantyl conjugates promote the degradation of the S1 spike domain, stably expressed in human cells by genomic insertion. These results highlight the suitability of aptamers as target-recognition molecules and the robustness of protein quality control pathways triggered by hydrophobic signals, and place aptamer-Hytacs as promising tools for counteracting coronavirus progression in human cells. [ABSTRACT FROM AUTHOR]

Objective: Pro-resolving molecules, including the peptide Angiotensin-(1–7) [Ang-(1–7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1–7) in betacoronavirus infection in mice. Methods: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1–7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1–7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated. Results: Ang-(1–7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1–7) during MHV infection. Ang-(1–7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1–7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates. Conclusion: Ang-(1–7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance. [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]

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Tissue-specific immune responses are critical determinants of health-maintaining homeostasis and disease-related dysbiosis. In the context of COVID-19, oral immune responses reflect local host-pathogen dynamics near the site of infection and serve as important "windows to the body," reflecting systemic responses to the invading SARS-CoV-2 virus. This study leveraged multiplex technology to characterize the salivary SARS-CoV-2–specific immunological landscape (37 cytokines/chemokines and 11 antibodies) during early infection. Cytokine/immune profiling was performed on unstimulated cleared whole saliva collected from 227 adult SARS-CoV-2+ participants and 37 controls. Statistical analysis and modeling revealed significant differential abundance of 25 cytokines (16 downregulated, 9 upregulated). Pathway analysis demonstrated early SARS-CoV-2 infection is associated with local suppression of oral type I/III interferon and blunted natural killer–/T-cell responses, reflecting a potential novel immune-evasion strategy enabling infection. This virus-associated immune suppression occurred concomitantly with significant upregulation of proinflammatory pathways including marked increases in the acute phase proteins pentraxin-3 and chitinase-3-like-1. Irrespective of SARS-CoV-2 infection, prior vaccination was associated with increased total α-SARS-CoV-2-spike (trimer), -S1 protein, -RBD, and -nucleocapsid salivary antibodies, highlighting the importance of COVID-19 vaccination in eliciting mucosal responses. Altogether, our findings highlight saliva as a stable and accessible biofluid for monitoring host responses to SARS-CoV-2 over time and suggest that oral-mucosal immune dysregulation is a hallmark of early SARS-CoV-2 infection, with possible implications for viral evasion mechanisms. [ABSTRACT FROM AUTHOR]

We study the impact of widespread adoption of work-from-home (WFH) technology using an equilibrium model where people choose where to live, how to allocate their time between working at home and at the office, and how much space to use in production. Motivated by cross-sectional evidence on WFH, we model WFH as a complement to work at the office. Simulations of the model indicate that the pandemic induced a large change to the relative productivity of WFH that substantially increased home prices and will permanently affect incomes, income inequality, and city structure. [ABSTRACT FROM AUTHOR]

Considering the presence of airborne viruses, there is a need for renovation in refuse chutes, regarded as the first step in recycling household waste in buildings. This study aimed to revise the design of existing refuse chutes in light of the challenging experiences in waste management and public health during the coronavirus pandemic. This research primarily focused on the risks posed by various types of coronaviruses, such as the novel coronavirus (COVID-19) and acute respiratory syndrome (SARS and SARS-CoV), on stainless steel surfaces, with evidence of their survival under certain conditions. Refuse chutes are manufactured from stainless steel to resist the corrosive effects of waste. In examining the existing studies, it was observed that Casanova et al. and Chowdhury et al. found that the survival time of coronaviruses on stainless steel surfaces decreases as the temperature increases. Based on these studies, mechanical revisions have been made to the sanitation system of the refuse chute, thus increasing the washing water temperature. Additionally, through mechanical improvements, an automatic solution spray entry is provided before the intake doors are opened. Furthermore, to understand airflow and clarify flow parameters related to airborne infection transmission on residential floors in buildings equipped with refuse chutes, a computational fluid dynamics (CFD) analysis was conducted using a sample three-story refuse chute system. Based on the simulation results, a fan motor was integrated into the system to prevent pathogens from affecting users on other floors through airflow. Thus, airborne pathogens were periodically expelled into the atmosphere via a fan shortly before the intake doors were opened, supported by a PLC unit. Additionally, the intake doors were electronically interlocked, ensuring that all other intake doors remained locked while any single door was in use, thereby ensuring user safety. In a sample refuse chute, numerical calculations were performed to evaluate parameters such as the static suitability of the chute body thickness, static compliance of the chute support dimensions, chute diameter, chute thickness, fan airflow rate, ventilation duct diameter, minimum rock wool thickness for human contact safety, and the required number of spare containers. Additionally, a MATLAB code was developed to facilitate these numerical calculations, with values optimized using the Fmincon function. This allowed for the easy calculation of outputs for the new refuse chute systems and enabled the conversion of existing systems, evaluating compatibility with the new design for cost-effective upgrades. This refuse chute design aims to serve as a resource for readers in case of infection risks and contribute to the literature. The new refuse chute design supports the global circular economy (CE) model by enabling waste disinfection under pandemic conditions and ensuring cleaner source separation and collection for recycling. Due to its adaptability to different pandemic conditions including pathogens beyond coronavirus and potential new virus strains, the designed system is intended to contribute to the global health framework. In addition to the health measures described, this study calls for future research on how evolving global health conditions might impact refuse chute design. [ABSTRACT FROM AUTHOR]