Does intensive follow-up increase days alive and well out of hospital in heart failure?

151 Figure 1Day after discharge from hospitalDid you feel well today?Please write yes or no.Weight, kg123456789101112131415161718192021222324252627282930 151 Table 1Baseline characteristicsBaseline characteristicsStandard Follow-UpN=9Intensive Follow-UpN=17Age (years)78 [69,81]74 [65,82]Gender [number of females (%)] 2 (22%)7 (41%)Rockwood Frailty Score (2 weeks pre admission) 3 [3,5]5 [3,5]Left Ventricular Systolic Function (%)Preserved 34%Mildly impaired 11%Moderately impaired 33%Severely impaired 22%Preserved 35%Mildly impaired 12%Moderately impaired 18%Severely impaired 35%NTproBNP ng/L4772 [2883,4859]9 88 [4333,14876]eGFR on discharge, ml/min/1.73m246 [35,63]51 [30,82]Comorbidity Number (in addition to HF)3 [2,4]5 [3,6]SBP, mmHg108 [106,111]110 [103,120]Number of people known COVID positive (%)0%6%Descriptive statistics are expressed as Median [IQR] or N (%).Abbreviations: eGFR: Estimated Glomerular Filtration Rate, HF: Heart failure, IQR: Inter-Quartile Range, NTproBNP: N-terminal prohormone of brain natriuretic peptide, SBP: Systolic Blood Pressure. 151 Table 2Effectiveness of intensive follow-upStandard Follow-UpIntensive Follow-UpDays alive and well out of hospital12 [8,25]22 [15,28]Days with weight recorded27 [14,30]27 [7,30]ACEi, ARB, or entresto (%)6 (67%)14 (82%)Beta-Blocker (%)8 (89%)16 (94%)% max. dose of Beta-Blocker 44 [25,53]50 [34,100]MRA%5 (56%)9 (53%)Dose of MRA, mg25 [25,25]25 [25, 25]SGLT2 inhibitor (on Dapaglifozin or empaglifozin) (%)5 (56%)14 (82%)Total number of Disease Modifying Agents (max 4)3 [2,4]3 [3,4]Descriptive statistics are expressed as Median [IQR] or N (%).Abbreviations: ACEi: Angiotensin Converting Enzyme Inhibitor, ARB: Angiotensin Receptor Blocker, IQR: Inter-Quartile Range, MRA: Mineralocorticoid receptor antagonist, SGLT2 inhibitors: Sodium-glucose cotransporter-2 inhibitors.Conflict of InterestNone

Association among Lifestyle and Risk Factors with SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) has become a major health burden worldwide, with over 600 million confirmed cases and 6 million deaths by 15 December 2022. Although the acute phase of COVID-19 management has been established, the long-term clinical course and complications due to the relatively short outbreak is yet to be assessed. The current COVID-19 pandemic is causing significant morbidity and mortality around the world. Interestingly, epidemiological studies have shown that fatality rates vary considerably across different countries, and men and elderly patients are at higher risk of developing severe diseases. There is increasing evidence that COVID-19 infection causes neurological deficits in a substantial proportion to patients suffering from acute respiratory distress syndrome. Furthermore, lack of physical activity and smoking are associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) susceptibility. We should therefore explore why lack of physical activity, smoking, etc causing a population more susceptible to SARS-CoV-2 infection, and mechanism involved. Thus, in this review article, we summarize epidemiological evidence related to risk factors and lifestyle that affect COVID-19 severity and the mechanism involved. These risk factors or lifestyle interventions include smoking, cardiovascular health, obesity, exercise, environmental pollution, psychosocial social stress, and diet.

A receptor-binding domain-based nanoparticle vaccine elicits durable neutralizing antibody responses against SARS-CoV-2 and variants of concern.

Numerous vaccines have been developed to address the current COVID-19 pandemic, but safety, cross-neutralizing efficacy, and long-term protectivity of currently approved vaccines are still important issues. In this study, we developed a subunit vaccine, ASD254, by using a nanoparticle vaccine platform to encapsulate the SARS-CoV-2 spike receptor-binding domain (RBD) protein. As compared with the aluminum-adjuvant RBD vaccine, ASD254 induced higher titers of RBD-specific antibodies and generated 10- to 30-fold more neutralizing antibodies. Mice vaccinated with ASD254 showed protective immune responses against SARS-CoV-2 challenge, with undetectable infectious viral loads and reduced typical lesions in lung. Besides, neutralizing antibodies in vaccinated mice lasted for at least one year and were effective against various SARS-CoV-2 variants of concern, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, particle size, polydispersity index, and zeta potential of ASD254 remained stable after 8-month storage at 4°C. Thus, ASD254 is a promising nanoparticle vaccine with good immunogenicity and stability to be developed as an effective vaccine option in controlling upcoming waves of COVID-19.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.

County-Level Social Vulnerability is Associated With In-Hospital Death and Major Adverse Cardiovascular Events in Patients Hospitalized With COVID-19: An Analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry.

BACKGROUND: The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the United States. However, it is unknown whether hospitalized patients with COVID-19 from socially vulnerable communities experience higher rates of death and/or major adverse cardiovascular events (MACEs). Thus, we evaluated the association between county-level social vulnerability and in-hospital mortality and MACE in a national cohort of hospitalized COVID-19 patients. METHODS: Our study population included patients with COVID-19 in the American Heart Association COVID-19 Cardiovascular Disease Registry across 107 US hospitals between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Centers for Disease Control and Prevention, was used to classify the county-level social vulnerability of patients' place of residence. We fit a hierarchical logistic regression model with hospital-level random intercepts to evaluate the association of SVI with in-hospital mortality and MACE. RESULTS: Among 16 939 hospitalized COVID-19 patients in the registry, 5065 (29.9%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in the lowest quartile of SVI, patients in the highest quartile were younger (age 60.2 versus 62.3 years) and more likely to be Black adults (36.7% versus 12.2%) and Medicaid-insured (31.1% versus 23.0%). After adjustment for demographics (age, sex, race/ethnicity) and insurance status, the highest quartile of SVI (compared with the lowest) was associated with higher likelihood of in-hospital mortality (OR, 1.25 [1.03-1.53]; P=0.03) and MACE (OR, 1.26 [95% CI, 1.05-1.50]; P=0.01). These findings were not attenuated after accounting for clinical comorbidities and acuity of illness on admission. CONCLUSIONS: Patients hospitalized with COVID-19 residing in more socially vulnerable communities experienced higher rates of in-hospital mortality and MACE, independent of race, ethnicity, and several clinical factors. Clinical and health system strategies are needed to improve health outcomes for socially vulnerable patients.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19.

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.

Temporal trends in the association of social vulnerability and race/ethnicity with county-level COVID-19 incidence and outcomes in the USA: an ecological analysis.

BACKGROUND: The COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the USA initially, but the temporal trends during the year-long pandemic remain unknown. OBJECTIVE: We examined the temporal association of county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the USA in the year starting in March 2020. METHODS: Counties (n=3091) with ≥50 COVID-19 cases by 6 March 2021 were included in the study. Associations between SVI (and its subcomponents) and county-level racial composition with incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time-varying associations between weekly number of cases/deaths and SVI or racial composition. Data were adjusted for percentage of population aged ≥65 years, state-level testing rate, comorbidities using the average Hierarchical Condition Category score, and environmental factors including average fine particulate matter of diameter ≥2.5 µm, temperature and precipitation. RESULTS: Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio per 10 percentile increase: 1.02, 95% CI 1.02 to 1.03, p<0.001) and death per capita (1.04, 95% CI 1.04 to 1.05, p<0.001). SVI became an independent predictor of incidence starting from March 2020, but this association became weak or insignificant by the winter, a period that coincided with a sharp increase in infection rates and mortality, and when counties with higher proportion of white residents were disproportionately represented ('third wave'). By spring of 2021, SVI was again a predictor of COVID-19 outcomes. Counties with greater proportion of black residents also observed similar temporal trends in COVID-19-related adverse outcomes. Counties with greater proportion of Hispanic residents had worse outcomes throughout the duration of the analysis. CONCLUSION: Except for the winter 'third wave', when majority of the white communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations experienced worse COVID-19 outcomes.

Post-Pandemic Patient Safety Culture: A Case from a Large Metropolitan Hospital Group in Taiwan.

Patient safety is the core goal of medical institutions. The present study focuses on the patient safety culture and staff well-being admit the COVID-19 pandemic. In a large metropolitan hospital group, 337 employees who had participated in the quality improvement interventions completed an anonymous questionnaire of patient safety culture and personal well-being. The multiple regression analyses indicated that managerial role, seniority, female gender and direct contact with a patient were significantly related to the positive attitude on overall or certain dimensions of safety culture. Multivariate analysis also found that dimensions of teamwork climate, safety climate, job satisfaction and stress recognition as patient safety culture predicted staff exhaustion. Finally, comparing with the available institutional historic data in 2018, the COVID group scored higher on the working condition dimension of patient safety culture, but lower on the stress recognition dimension. The COVID group also scored higher on exhaustion. In the post-pandemic era, there seems to be an improvement on certain aspect of the patient safety culture among hospital staff, and the improvement is more prevalent for managers. However, exhaustion is also a poignant problem for all employees. These findings can inform hospital decision-makers in planning and implementing future improvements of patient safety culture and promoting employee well-being and resilience. Our findings also reveal directions for future research.