Hypertension is the most important contributor to the development of cardiovascular disease. The objective of the Bring it Down program was to examine the reach and effectiveness of linkage to primary care via community health workers (CHWs) to improve blood pressure control among people with undiagnosed or uncontrolled hypertension. Adults with systolic blood pressures ≥130 mmHg were initially recruited from four urban emergency departments that serve high-risk, socially vulnerable populations. Due to the COVID-19 pandemic, we also enrolled participants in the community who presented to mobile health units. CHWs facilitated follow-up blood pressure assessment within 1 year. Of 153 630 ED patient encounters during the evaluation period, 61% were eligible to participate in the BID program; of these, 3% were approached, and 16% (395/2476) agreed to participate. Compared to ED encounters, fewer patients presenting to MHUs were eligible to participate (42%, 1780/4211), all of whom were approached, and 7% (124/1780) agreed to participate in the BID program. Among participants with at least one follow-up encounter (n = 158), there was a statistically significant reduction in mean systolic BP (mean difference: -16 mmHg, 99% confidence intervals (CI): -21, -12 mmHg) with a median time between SBP measurements of 20 days (interquartile range [IQR]: 8, 53 days). Clinical and community recruitment paired with CHW connections to primary care may be a viable quality improvement strategy for improving blood pressure control in high-risk, socially vulnerable populations. However, additional research is needed to understand and improve participation and follow-up rates to establish program effectiveness.

Estimating global lives and life-years saved is important to put into perspective the benefits of COVID-19 vaccination. Prior studies have focused mainly on the pre-Omicron period or only on specific regions, and lack crucial life-year calculations and often depend on strong modeling assumptions with unaccounted uncertainty.

To calculate the lives and life-years saved by COVID-19 vaccination worldwide from the onset of the vaccination campaigns and until October 1, 2024.

This comparative effectiveness study considered different strata of the worldwide population according to age, community-dwelling and long-term care residence status, pre-Omicron and Omicron periods, and vaccination before and after a SARS-CoV-2 infection.

Any COVID-19 vaccination in any schedule and number of doses.

Death.

In the main analysis, more than 2.5 million deaths were averted (1 death averted per 5400 vaccine doses administered). Eighty-two percent were among people vaccinated before any infection, 57% were during the Omicron period, and 90% pertained to people 60 years or older. Sensitivity analyses suggested 1.4 to 4.0 million lives were saved. Some sensitivity analyses showed a preponderance of the benefit during the pre-Omicron period. An estimated 14.8 million life-years were saved (1 life-year saved per 900 vaccine doses administered). The sensitivity range was 7.4 to 23.6 million life-years. Most life-years saved (76%) were among people 60 years or older, but long-term care residents contributed only 2% of the total. Children and adolescents (0.01% of lives saved and 0.1% of life-years saved) and young adults aged 20 through 29 years (0.07% of lives saved and 0.3% of life-years saved) had very small contributions to the total benefit.

Estimates in this study are substantially more conservative than previous calculations focusing mostly on the first year of vaccination, but they still clearly demonstrate a major overall benefit from COVID-19 vaccination during the years 2020-2024. Most benefits in lives and life-years saved was secured for a portion of older persons, a minority of the global population.

The complex pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves a hyperinflammatory state with excessive cytokine production, leading to an influenza-like syndrome that may need emergency care. The severity of SARS-CoV-2 varies widely, and collective serum immune factors, evaluated in emergency care patients, have not been shown to correlate with disease progression. We applied a machine learning approach to reassess and define serum immune profiles that could align with clinical laboratory parameters and predict disease outcomes in patients with respiratory virus infections, including those with SARS-CoV-2, seeking emergency care. Sixty-two plasma immune molecules, in a cohort of 67 symptomatic SARS-CoV-2, were analyzed for correlation with antibodies (Abs) to spike (S) and nucleocapsid (N) proteins, as well as with clinical laboratory parameters, to identify early indicators of disease prognosis at hospital admission. This approach allowed us to analyze and cluster unlabeled datasets, delineating three distinct serum immune signatures. Two showed significant and opposite modulations, correlating with poorer disease outcomes, while most patients with moderate disease displayed modest immune factor dysregulation. This highlights the complexity of immune responses in the severity of diseases caused by highly respiratory pathogenic virus like SARS-CoV-2, emphasizing the importance of evaluating overall immune imbalance rather than focusing on a few dysregulated factors.

Innate immune cells appear to have an important implication in the resolution and/or the aggravation of the COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, the neutrophil and monocyte count, and levels of surface protein markers have been reported. However, analyses at several timepoints of multiple surface markers on granulocytes and monocytes over a period of one month after a SARS-CoV-2 infection are missing. Therefore, in this study, we performed blood eosinophil, neutrophil, and monocyte phenotyping using a list of surface proteins and flow cytometry during a period of 30 days after the hospitalization of patients with severe SARS-CoV-2 infections. Blood cell counts were reported at seven different timepoints over the 30-day period as well as measures of multiple mediators in serum using a targeted multiplex assay approach. Our results indicate a 95% drop in the blood eosinophil count by D1, with eosinophils displaying a phenotype defined as CD69/CD63/CD125^high and CCR3/CD44^low during the early phases of hospitalization. Conversely, by D7 the neutrophil count increased significantly and displayed an immature, activated, and immunosuppressive phenotype (i.e., 3% of CD10/CD16^low and CD10^lowCD177^high, 6.7% of CD11b^highCD62L^low, and 1.6% of CD16^highCD62L^low), corroborated by enhanced serum proteins that are markers of neutrophil activation. Finally, our results suggest a rapid recruitment of non-classical monocytes leaving CD163/CD64^high and CD32^low monocytes in circulation during the very early phase. In conclusion, our study reveals potential very early roles for eosinophils and monocytes in the pathogenesis of COVID-19 with a likely reprogramming of eosinophils in the bone marrow. The exact roles of the pro-inflammatory neutrophils and the functions of the eosinophils and the monocytes, as well as these innate immune cell types, interplays need to be further investigated.

Acute lung injury (ALI), a life-threatening clinical syndrome with multifactorial origins, is characterized by uncontrolled pulmonary inflammation and disrupted alveolar-capillary barrier integrity, leading to progressive hypoxemia and respiratory failure. In this hypoxic setting, hypoxia-inducible factor (HIF)-1 is activated, acting as a central regulator of the inflammatory response and reparative processes in injured lung tissue during ALI. The role of HIF-1 is distinctly dualistic; it promotes both anti-inflammatory and reparative mechanisms to a certain extent, while potentially exacerbating inflammation, thus having a complex impact on disease progression. We explore the latest understanding of the role of hypoxia/HIF-mediated inflammatory and reparative pathways in ALI and consider the potential therapeutic applications of drugs targeting these pathways for the development of innovative treatment strategies. Therefore, this review aims to guide future research and clinical applications by emphasizing HIF-1 as a key therapeutic target for ALI.

Upper respiratory tract infections (URTI) and the associated symptoms can have significant impacts for the general population and athletes (e.g., affecting training, recovery, and performance). Various factors influence the risk of URTI, including physiological stress (i.e., exercise), psychological stress, sleep, travel, nutrition, and pathogen exposure. Traditional research in exercise immunology has relied heavily on ex vivo immune markers, which lack clinical relevance and overlook immune redundancy and robustness. As such, it is unsurprising that interventions affecting these markers do not always align with URTI risk. More recently, evidence has emphasized the importance of in vivo immune markers and clinical outcomes to assess infection risk, and the role of interventions to mitigate this. Traditionally, nutritional exercise immunology research has focused only on mechanisms affecting URTI via immune modulation. However, nutritional interventions may also act via immune-independent mechanisms (e.g., direct antipathogenic mechanisms). For future research, we recommend prioritizing clinically relevant endpoints (validated URTI logs; pathogen screening); using in vivo markers representing the integrated immune response; large sample size; and implementing stringent study controls. Experimental infection challenge models offer controlled investigations of interventions. These approaches will enhance our ability to determine the impact of exercise and nutrition on immunity and URTI outcomes in athletes.

Acute kidney injury (AKI) is a common and severe complication of COVID-19, which significantly increases the risk of mortality. There has been a wide range of AKI prevalence reported throughout the pandemic, reflecting differences in geographic location, patient characteristics, and health care resources. We aimed to provide a global overview of the COVID-19 AKI prevalence reported in published studies to uncover geographic and socioeconomic disparities.

We undertook a systematic review and meta-analysis, searching PubMed, Embase, Scopus, Web of Science, and Cochrane Library for full-text articles published in English reporting the prevalence of AKI from January 2020 to November 2023. All studies defined AKI according to the Kidney Disease Improving Global Outcomes criteria. Clinical characteristics were extracted and examined from 334 studies that met the inclusion criteria. With significant study heterogeneity, random-effect models were estimated. We reported pooled AKI prevalence by country, region, and income level. Meta-regression further examined the relationship between COVID-associated AKI and geographic location.

After removing studies that utilised the same data, 345 796 patients from 246 studies were included, covering 49 countries. Of 246 studies, 137 came from high-income countries, whereas only three were conducted in low-income countries. Among non-intensive care unit (ICU) patients, low-income countries had the lowest COVID-19 AKI prevalence (14.1%; 95% confidence interval (CI) = 11.4-17.2). Among ICU patients, lower-middle-income countries had the lowest COVID-19 AKI prevalence (27.9%;95% CI = 19.4-38.4).

Our study shows significant geographic and socioeconomic disparities in the prevalence of COVID-associated AKI, with a higher prevalence in high-income countries and a lower prevalence in low- and lower-middle-income countries. This study is the most comprehensive systematic review and meta-analysis highlighting global disparities in COVID-associated AKI prevalence. Further studies are needed to explain the reasons behind these differences.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly after its identification in December 2019 to cause a global pandemic. The respiratory tract is the primary site of infection, and there is a large range in the severity of respiratory illnesses caused by the virus. Defining molecular and cellular factors for protection from severe disease and death has been a goal to better understand and to predict and mitigate the effects of SARS-CoV-2 and future coronaviruses.

Despite well-known susceptibilities to respiratory viral infections, respiratory allergy and allergic asthma have not been identified as risk factors for severe coronavirus disease 2019 (COVID-19) in most epidemiologic studies and may be protective. We sought to investigate associations between markers of type 2 (T2) immune responses with SARS-CoV-2 clinical outcomes and virus loads in a cohort of 1164 individuals hospitalized for COVID-19 from May 2020 to March 2021 as part of the IMPACC study.

We characterized the clinical outcomes, as defined by severity trajectory groups reflecting the degree of respiratory support required, virus loads, and antibody titers of COVID-19 infections in IMPACC participants in relation to molecular and cellular markers of T2 immune responses through multiple assays, including, (1) IL-4, IL-5, and IL-13 levels in serum Olink data, (2) T2 cellular signatures in blood cytometry by time of flight data, (3) relative quantification of T2 signaling gene pathways in airway RNA sequencing data, and/or (4) T2 pathways in peripheral blood mononuclear cell RNA sequencing data. We also investigated the outcomes of individuals with self-reported asthma and evidence of T2 immune responses.

The diagnosis of asthma (odd ratio = 1.27), elevated serum T2 cytokine levels (median fold change = 1.06), and a higher frequency of T_H2 cells (difference = +2%) were associated with less severe clinical disease during hospitalization. Distinct T2-related transcriptomic changes in nasal and blood samples were associated with reduced virus loads. This included the expression of T2-regulated genes implicated in T-/B-cell activation and apoptosis in nasal samples and the expression of T2-regulated genes implicated in myeloid differentiation and reactive oxygen species signaling in blood. Among these, several canonical T2-regulated genes that were increased in less severe disease were identified to have antiviral properties in large high-throughput screens.

T2 immune responses were associated with lower virus loads and more favorable clinical outcomes, suggesting that T2 inflammation related to asthma and allergic diseases may have a direct protective effect against SARS-CoV-2.

The rapid spread of infectious diseases presents a significant global threat, with seasonal influenza viruses, leading to 290,000-650,000 deaths annually. Emerging high pathogenic influenza strains from animals such as H5N1 and H7N9 further exacerbates pandemic risks. While developing effective vaccines and therapeutics is critical, the evaluation of these interventions is constrained by the requirement for high biosafety containment facilities. To circumvent these challenges, we developed S-Lux, a replication-deficient, single-cycle recombinant influenza virus expressing firefly luciferase (Flux) as a reporter protein. S-Lux can be pseudotyped with haemagglutinin from avian influenza, H5 and H7, enabling real-time monitoring of viral infection in vivo, and facilitate therapeutic antibody evaluation in low-containment facilities. In mice, S-Lux infection resulted in dose-dependent bioluminescent expression in the mouse airways and allowed evaluation of neutralising monoclonal antibodies and clearance of infected cells in mice. To extend this system, we generated ES-Lux by pseudotyping with the Ebola Glycoprotein (GP) and demonstrated that ES-Lux can be used to evaluate the efficacy of Ebola GP-targeting antibodies in vivo. Together, S-Lux and ES-Lux enable robust, simple and time-efficient assessment of antiviral therapy targeting influenza and Ebola virus in vivo, overcoming biosafety constraints that limit traditional efficacy studies.

Regulatory B cells (Breg) critically orchestrate inflammatory resolution and tissue repair. This study investigates the therapeutic potential of transforming growth factor (TGF)-β1-producing Bregs in ventilator-induced lung injury (VILI), leveraging biomimetic nanotechnology to overcome limitations of conventional cytokine delivery.

We engineered macrophage-derived microvesicle-encapsulated nanoparticles (TMNP) for pH-responsive, spatiotemporally controlled TGF-β1 release. Therapeutic efficacy was evaluated in a murine VILI model through longitudinal immunophenotyping, histopathology, and cytokine profiling at post-ventilation days 1 and 10 (PV1d, PV10d).

VILI triggered biphasic pulmonary Breg expansion (PV1d: 7.83-fold vs. controls, P < 0.001; PV10d resurgence) coinciding with peak injury. TMNP administration induced sustained TGF-β1 bioavailability (PV10d: 3.6-fold vs. free cytokine, P < 0.001), attenuating histopathology (22.5% reduction in alveolar hemorrhage, P < 0.01) and suppressing IL-6/TNF-α (P < 0.01). Treatment concomitantly expanded Breg populations and modulated T cell subset.

TMNP orchestrates Breg-mediated immunoresolution through precision cytokine delivery and lymphocyte modulation, enabling dual-phase protection against ventilation-associated immunopathology. This paradigm represents a transformative approach for acute respiratory distress management.