Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis.

The glycerol-3-phosphate shuttle (G3PS) is a major NADH shuttle that regenerates reducing equivalents in the cytosol and produces energy in the mitochondria. Here, we demonstrate that G3PS is uncoupled in kidney cancer cells where the cytosolic reaction is ∼4.5 times faster than the mitochondrial reaction. The high flux through cytosolic glycerol-3-phosphate dehydrogenase (GPD) is required to maintain redox balance and support lipid synthesis. Interestingly, inhibition of G3PS by knocking down mitochondrial GPD (GPD2) has no effect on mitochondrial respiration. Instead, loss of GPD2 upregulates cytosolic GPD on a transcriptional level and promotes cancer cell proliferation by increasing glycerol-3-phosphate supply. The proliferative advantage of GPD2 knockdown tumor can be abolished by pharmacologic inhibition of lipid synthesis. Taken together, our results suggest that G3PS is not required to run as an intact NADH shuttle but is instead truncated to support complex lipid synthesis in kidney cancer.

Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.

Long-term exposure to ambient ozone at workplace is positively and non-linearly associated with incident hypertension and blood pressure: longitudinal evidence from the Beijing-Tianjin-Hebei medical examination cohort.

BACKGROUND: There is limited longitudinal evidence on the hypertensive effects of long-term exposure to ambient O3. We investigated the association between long-term O3 exposure at workplace and incident hypertension, diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), and mean arterial pressure (MAP) in general working adults. METHODS: We conducted a cohort study by recruiting over 30,000 medical examination attendees through multistage stratified cluster sampling. Participants completed a standard questionnaire and comprehensive medical examination. Three-year ambient O3 concentrations at each employed participant's workplace were estimated using a two-stage machine learning model. Mixed-effects Cox proportional hazards models and linear mixed-effects models were used to examine the effect of O3 concentrations on incident hypertension and blood pressure parameters, respectively. Generalized additive mixed models were used to explore non-linear concentration-response relationships. RESULTS: A total of 16,630 hypertension-free working participants at baseline finished the follow-up. The mean (SD) O3 exposure was 45.26 (2.70) ppb. The cumulative incidence of hypertension was 7.11 (95% CI: 6.76, 7.47) per 100 person-years. Long-term O3 exposure was independently, positively and non-linearly associated with incident hypertension (Hazard ratios (95% CI) for Q2, Q3, and Q4 were 1.77 (1.34, 2.36), 2.06 (1.42, 3.00) and 3.43 (2.46, 4.79), respectively, as compared with the first quartile (Q1)), DBP (ß (95% CI) was 0.65 (0.01, 1.30) for Q2, as compared to Q1), SBP (ß (95% CI) was 2.88 (2.00, 3.77), 2.49 (1.36, 3.61) and 2.61 (1.64, 3.58) for Q2, Q3, and Q4, respectively), PP (ß (95% CI) was 2.12 (1.36, 2.87), 2.03 (1.18, 2.87) and 2.14 (1.38, 2.90) for Q2, Q3, and Q4, respectively), and MAP (ß (95% CI) was 1.39 (0.76, 2.02), 1.04 (0.24, 1.84) and 1.12 (0.43, 1.82) for Q2, Q3, and Q4, respectively). The associations were robust across sex, age, BMI, and when considering PM2.5 and NO2. CONCLUSIONS: To our knowledge, this is the first cohort study in the general population that demonstrates the non-linear hypertensive effects of long-term O3 exposure. The findings are particularly relevant for policymakers and researchers involved in ambient pollution and public health, supporting the integration of reduction of ambient O3 into public health interventions.

Mobile device data reveal the dynamics in a positive relationship between human mobility and COVID-19 infections.

Accurately estimating human mobility and gauging its relationship with virus transmission is critical for the control of COVID-19 spreading. Using mobile device location data of over 100 million monthly active samples, we compute origin-destination travel demand and aggregate mobility inflow at each US county from March 1 to June 9, 2020. Then, we quantify the change of mobility inflow across the nation and statistically model the time-varying relationship between inflow and the infections. We find that external travel to other counties decreased by 35% soon after the nation entered the emergency situation, but recovered rapidly during the partial reopening phase. Moreover, our simultaneous equations analysis highlights the dynamics in a positive relationship between mobility inflow and the number of infections during the COVID-19 onset. This relationship is found to be increasingly stronger in partially reopened regions. Our study provides a quick reference and timely data availability for researchers and decision makers to understand the national mobility trends before and during the pandemic. The modeling results can be used to predict mobility and transmissions risks and integrated with epidemics models to further assess the public health outcomes.

Interactive COVID-19 Mobility Impact and Social Distancing Analysis Platform.

The research team has utilized privacy-protected mobile device location data, integrated with COVID-19 case data and census population data, to produce a COVID-19 impact analysis platform that can inform users about the effects of COVID-19 spread and government orders on mobility and social distancing. The platform is being updated daily, to continuously inform decision-makers about the impacts of COVID-19 on their communities, using an interactive analytical tool. The research team has processed anonymized mobile device location data to identify trips and produced a set of variables, including social distancing index, percentage of people staying at home, visits to work and non-work locations, out-of-town trips, and trip distance. The results are aggregated to county and state levels to protect privacy, and scaled to the entire population of each county and state. The research team is making their data and findings, which are updated daily and go back to January 1, 2020, for benchmarking, available to the public to help public officials make informed decisions. This paper presents a summary of the platform and describes the methodology used to process data and produce the platform metrics.

A big-data driven approach to analyzing and modeling human mobility trend under non-pharmaceutical interventions during COVID-19 pandemic.

During the unprecedented coronavirus disease 2019 (COVID-19) challenge, non-pharmaceutical interventions became a widely adopted strategy to limit physical movements and interactions to mitigate virus transmissions. For situational awareness and decision-support, quickly available yet accurate big-data analytics about human mobility and social distancing is invaluable to agencies and decision-makers. This paper presents a big-data-driven analytical framework that ingests terabytes of data on a daily basis and quantitatively assesses the human mobility trend during COVID-19. Using mobile device location data of over 150 million monthly active samples in the United States (U.S.), the study successfully measures human mobility with three main metrics at the county level: daily average number of trips per person; daily average person-miles traveled; and daily percentage of residents staying home. A set of generalized additive mixed models is employed to disentangle the policy effect on human mobility from other confounding effects including virus effect, socio-demographic effect, weather effect, industry effect, and spatiotemporal autocorrelation. Results reveal the policy plays a limited, time-decreasing, and region-specific effect on human movement. The stay-at-home orders only contribute to a 3.5%-7.9% decrease in human mobility, while the reopening guidelines lead to a 1.6%-5.2% mobility increase. Results also indicate a reasonable spatial heterogeneity among the U.S. counties, wherein the number of confirmed COVID-19 cases, income levels, industry structure, age and racial distribution play important roles. The data informatics generated by the framework are made available to the public for a timely understanding of mobility trends and policy effects, as well as for time-sensitive decision support to further contain the spread of the virus.

Examining spatiotemporal changing patterns of bike-sharing usage during COVID-19 pandemic.

The COVID-19 pandemic has led to a globally unprecedented change in human mobility. Leveraging two-year bike-sharing trips from the largest bike-sharing program in Chicago, this study examines the spatiotemporal evolution of bike-sharing usage across the pandemic and compares it with other modes of transport. A set of generalized additive (mixed) models are fitted to identify relationships and delineate nonlinear temporal interactions between station-level daily bike-sharing usage and various independent variables including socio-demographics, land use, transportation features, station characteristics, and COVID-19 infections. Results show: 1) the proportion of commuting trips is substantially lower during the pandemic; 2) the trend of bike-sharing usage follows an "increase-decrease-rebound" pattern; 3) bike-sharing presents as a more resilient option compared with transit, driving, and walking; 4) regions with more white, Asian, and fewer African-American residents are found to become less dependent on bike-sharing; 5) open space and residential areas exhibit less decrease and earlier start-to-recover time; 6) stations near the city center, with more docks, or located in high-income areas go from more increase before the pandemic to more decrease during the pandemic. Findings provide a timely understanding of bike-sharing usage changes and offer suggestions on how different stakeholders should respond to this unprecedented crisis.

Ginseng stem-leaf saponins in combination with selenium enhance immune responses to an attenuated pseudorabies virus vaccine.

Pseudorabies, a herpesvirus infection, is mainly controlled by using attenuated live vaccines. In this study, the effect of ginseng stem and leaf saponins (GSLS) in combination with selenium (Se; in the form of sodium selenite) on vaccination against attenuated pseudorabies virus (aPrV) was evaluated. It was found that GSLS and Se have an adjuvant effect and that a combination of GSLS and Se stimulates significantly enhanced immune responses than does GSLS or Se alone. Following oral administration of GSLS, mice immunized with an attenuated PrV vaccine diluted in Se-containing physiological saline solution (PSS) provoked a significantly stronger gB-specific serum antibodies response (IgG, IgG1 and IgG2a), enhanced lymphocyte proliferation and cytolytic activity of NK cells, along with higher production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) by splenocytes. Notably, the combination of GSLS and Se conferred a much higher resistance to fPrV challenge after immunization of the mice with aPrV vaccine. This study offers convincing experimental evidence that an injection of Se with oral GSLS is a promising adjuvant combination that improves the efficacy of vaccination against PrV and deserves further study regarding improvement of responses to other animal vaccines.

Soybean oil containing ginseng saponins as adjuvants promotes production of cytokines and enhances immune responses to foot-and-mouth disease vaccine.

In the present study, the adjuvant effect of soybean oil containing ginseng root saponins (SO-GS-R) on the immune response to foot-and-mouth disease vaccine (FMDV) in mice was investigated. When immunized with FMDV antigen emulsified in an SO-GS-R formulation, mice generated remarkably higher serum antibody and cytokine responses than mice immunized with FMDV antigen alone. To elucidate the mechanisms underlying the adjuvant effect of SO-GS-R, we measured cytokines in serum and muscle tissue after intramuscular injection of SO-GS-R. The results showed that injection of SO-GS-R significantly increased the levels of IL-1ß, IL-5, IL-6, G-CSF, KC, MCP-1, MIP-1α, and MIP-1ß in both serum and muscle. These results suggested that SO-GS-R recruits neutrophils, eosinophils, T cells and macrophages, causing immune cell recruitment at the injection site, driving antigen-presenting cells to actively participate in the onset of immunity, and amplifying the immune responses. Considering its adjuvant activity and plant-derived properties, SO-GS-R should be further studied for its adjuvant effect on vaccines used in food animals.

Enhanced immune response to foot-and-mouth disease vaccine by oral administration of ginseng stem-leaf saponins.

Vaccination is an important approach to the control of foot-and-mouth disease (FMD). This study evaluated the effect of oral administration of ginseng stem-leaf saponins (GSLS) on the immune response to FMD vaccine and the gut mucosal immunity in mice. In experiment 1, mice were orally administered GSLS or not treated as a control. The animals were then immunized twice with FMD vaccine. Blood was sampled weekly within five weeks after the boost immunization for measurement of serum IgG and the isotypes. In experiment 2, mice were orally administrated GSLS or not treated as a control. After that, splenocytes were prepared from sacrificed mice for lymphocyte proliferation assay and intestinal tissues were sampled for immunohistochemistry and histological examination. The results showed that oral administration of GSLS significantly enhanced serum IgG and the isotype responses to FMD vaccine as well as the number of intestinal intraepithelial lymphocytes (IELs) and immunoglobulin A (IgA)+ cells. Therefore, GSLS may be a potent oral adjuvant and deserve further study to improve vaccination in susceptible animals.

Protective effect of ginsenosides Rg1 and Re on lipopolysaccharide-induced sepsis by competitive binding to Toll-like receptor 4.

We previously demonstrated that ginsenosides Rg1 and Re enhanced the immune response in C3H/HeB mice but not in C3H/HeJ mice carrying a mutation in the Tlr4 gene. The results of the present study showed that both Rg1 and Re inhibited mRNA expression and production of proinflammatory mediators that included tumor necrosis factor α, interleukin-1ß, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase from lipopolysaccharide (LPS)-stimulated macrophages. Rg1 was found to be distributed both extracellularly and intracellularly but Re was located only extracellularly to compete with LPS for binding to Toll-like receptor 4. Preinjection of Rg1 and Re into rats suppressed LPS-induced increases in body temperature, white blood cell counts, and levels of serum proinflammatory mediators. Preinjection of Rg1 and Re into mice prevented the LPS-induced decreases in total white blood cell counts and neutrophil counts, inhibited excessive expression of multiple proinflammatory mediators, and successfully rescued 100% of the mice from sepsis-associated death. More significantly, when administered after lethal LPS inoculation, Rg1, but not Re, still showed a potent antisepsis effect and protected 90% of the mice from death. The better protection efficacy of Rg1 could result from its intracellular distribution, suggesting that Rg1 may be an ideal antisepsis agent.

Therapeutic effect of polysaccharide fraction of Atractylodis macrocephalae Koidz. in bovine subclinical mastitis.

BACKGROUND: Mastitis is considered the most significant and persistent disease in dairy cows, bringing about large economic losses. Subclinical mastitis brings about major cost implications, for it is difficult to detect due to absence of any visible indications and can persist in the mammary tissue throughout lactation. Immunomodulators have been widely used to reduce intramammary infections by modulating bovine mammary gland. Atractylodis macrocephalae Koidz. polysaccharides (RAMP), extracted from herbal medicine, has been used widely especially for its immunomodulatory function for many years. The objective of this study was to estimate an oil emulsified Atractylodis macrocephalae Koidz. polysaccharides (RAMP-O) as a potential therapeutic agent to treat subclinical mastitis by subcutaneous injection of RAMP-O in the area of supramammary lymph node in lactating cows via analysis of SCC, IMIs and NAGase. RESULTS: Injection of RAMP-O in the area of supramammary lymph node significantly reduced milk SCC and NAGase activity compared with control. The quarters with bacterial infection were also progressively reduced in RAMP-O treated cows and only 9 quarters were found to have bacterial infection, while no obvious change was found in the control group. CONCLUSIONS: Subcutaneous injection of RAMP-O in the area of supramammary lymph node had therapeutic value in the treatment of bovine subclinical mastitis by reducing SCC, NAGase and IMIs in milk. Considering both the therapeutic effect and the cost of RAMP-O, 32 mg per dose was found most suitable to reduce milk SCC and NAGase. Therefore, RAMP-O deserves further study for its use in treatment of bovine mastitis.

SIRT4 loss reprograms intestinal nucleotide metabolism to support proliferation following perturbation of homeostasis.

The intestine is a highly metabolic tissue, but the metabolic programs that influence intestinal crypt proliferation, differentiation, and regeneration are still emerging. Here, we investigate how mitochondrial sirtuin 4 (SIRT4) affects intestinal homeostasis. Intestinal SIRT4 loss promotes cell proliferation in the intestine following ionizing radiation (IR). SIRT4 functions as a tumor suppressor in a mouse model of intestinal cancer, and SIRT4 loss drives dysregulated glutamine and nucleotide metabolism in intestinal adenomas. Intestinal organoids lacking SIRT4 display increased proliferation after IR stress, along with increased glutamine uptake and a shift toward de novo nucleotide biosynthesis over salvage pathways. Inhibition of de novo nucleotide biosynthesis diminishes the growth advantage of SIRT4-deficient organoids after IR stress. This work establishes SIRT4 as a modulator of intestinal metabolism and homeostasis in the setting of DNA-damaging stress.

Widespread Neuroanatomical Integration and Distinct Electrophysiological Properties of Glioma-Innervating Neurons.

Gliomas are the most common malignant primary brain tumors and are often associated with severe neurological deficits and mortality. Unlike many cancers, gliomas rarely metastasize outside the brain, indicating a possible dependency on unique features of brain microenvironment. Synapses between neurons and glioma cells exist, suggesting that glioma cells rely on neuronal inputs and synaptic signaling for proliferation. Yet, the locations and properties of neurons that innervate gliomas have remained elusive. In this study, we utilized transsynaptic tracing with a pseudotyped, glycoprotein-deleted rabies virus to specifically infect TVA and glycoprotein-expressing human glioblastoma cells in an orthotopic xenograft mouse model, allowing us to identify the neurons that form synapses onto the gliomas. Comprehensive whole-brain mapping revealed that these glioma-innervating neurons (GINs) consistently arise at brain regions, including diverse neuromodulatory centers and specific cortical layers, known to project to the glioma locations. Molecular profiling revealed that these long-range cortical GINs are predominantly glutamatergic, and subsets express both glutamatergic and GABAergic markers, whereas local striatal GINs are largely GABAergic. Electrophysiological studies demonstrated that while GINs share passive intrinsic properties with cortex-innervating neurons, their action potential waveforms are altered. Our study introduces a novel method for identifying and mapping GINs and reveals their consistent integration into existing location-dependent neuronal network involving diverse neurotransmitters and neuromodulators. The observed intrinsic electrophysiological differences in GINs lay the groundwork for future investigations into how these alterations may correspond with the postsynaptic characteristics of glioma cells. Significance: We have developed a novel system utilizing rabies virus-based monosynaptic tracing to directly visualize neurons that synapse onto human glioma cells implanted in mouse brain. This approach enables the mapping and quantitative analysis of these glioma-innervating neurons (GINs) in the entire mouse brain and overcomes previous barriers of molecular and electrophysiological analysis of these neurons due to the inability to identify them. Our findings indicate that GINs integrate into existing neural networks in a location-specific manner. Long-range GINs are mostly glutamatergic, with a subset expressing both glutamatergic and GABAergic markers and local striatal GINs are GABAergic, highlighting a complex neuromodulatory profile. Additionally, GINs exhibit unique action potential characteristics, distinct from similarly selected neurons in non-tumor-bearing brains. This study provides new insights into neuronal adaptations in response to forming putative synapses onto glioma, elucidating the intricate synaptic relationship between GINs and gliomas.

Ketogenic diet-produced ß-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy.

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced ß-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD.

Stereospecificity of ginsenoside Rg3 in promotion of the immune response to ovalbumin in mice.

Our previous investigation demonstrated that ginsenoside Rg3 was active in promotion of the immune response. In this study, two epimers, 20(R)-Rg3 and 20(S)-Rg3, were compared for their adjuvant effects on the immune response against ovalbumin (OVA). BALB/c mice were immunized subcutaneously with 10 µg of OVA alone or with 10 µg of OVA mixed in 20(R)-Rg3 (50 µg) or 20(S)-Rg3 (50 µg) on days 1 and 15. Two weeks after the last immunization, blood was sampled to test IgG and the IgG subclasses as well as IFN-γ and IL-5; splenocytes were prepared to measure proliferative responses to stimulations with Con A, LPS and OVA and mRNA expressions of cytokines and transcription factors by reverse transcription-PCR. Results indicated that both 20(R)-Rg3 and 20(S)-Rg3 exhibited the adjuvant effect on OVA-induced immune responses. 20(R)-Rg3 promoted significantly higher serum-specific IgG and the IgG isotype responses in association with highly up-regulated serum IFN-γ and IL-5 than 20(S)-Rg3. In addition, 20(R)-Rg3 significantly enhanced splenocyte proliferative responses to Con A, LPS and OVA as well as mRNA expression of IFN-γ, IL-12, IL-4 and IL-10 and transcription factors T-bet and GATA-3 by splenocytes when compared with the 20(S)-Rg3. Therefore, ginsenoside Rg3 is stereospecific in stimulation of the immune response, and 20(R)-Rg3 has more potent adjuvant activity than 20(S)-Rg3.

Asymptomatic Broncholithiasis and Aspergillus Infection: A Case Report and Literature Review.

Broncholithiasis coupled with Aspergillus infection is a rare disease of the respiratory system with complex pathogenesis and non-specific clinical manifestations that can be easily confused with other types of infectious diseases of the respiratory system. The lack of pertinent clinical manifestations in patients increases the risk of clinical misdiagnosis, omission, and incorrect treatment plan selection, which can result in permanent lung structural alterations and lung function decompensation and ultimately harm the lung. We report a rare case of asymptomatic broncholithiasis coupled with Aspergillus infection that was treated at our hospital and discuss the pathophysiology, diagnosis, differential diagnosis, and prognostic follow-up course. Furthermore, relevant studies from China and other countries, including this case, were reviewed. We gathered eight reports, summarized their significant diagnoses and treatments for broncholithiasis and broncholithiasis coupled with Aspergillus infection, and discussed their clinical features. Our study may help improve physicians' awareness of these types of diseases and serve as a resource for future diagnosis and treatment.

Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease (ILD) without an identifiable cause. If not treated after diagnosis, the average life expectancy is 3-5 years. Currently approved drugs for the treatment of IPF are Pirfenidone and Nintedanib, as antifibrotic drugs, which can reduce the decline rate of forced vital capacity (FVC) and reduce the risk of acute exacerbation of IPF. However these drugs can not relieve the symptoms associated with IPF, nor improve the overall survival rate of IPF patients. We need to develop new, safe and effective drugs to treat pulmonary fibrosis. Previous studies have shown that cyclic nucleotides participate in the pathway and play an essential role in the process of pulmonary fibrosis. Phosphodiesterase (PDEs) is involved in cyclic nucleotide metabolism, so PDE inhibitors are candidates for pulmonary fibrosis. This paper reviews the research progress of PDE inhibitors related to pulmonary fibrosis, so as to provide ideas for the development of anti-pulmonary fibrosis drugs.

Vaccination, human mobility, and COVID-19 health outcomes: Empirical comparison before and during the outbreak of SARS-Cov-2 B.1.1.529 (Omicron) variant.

The B.1.1.529 (Omicron) variant surge has raised concerns about the effectiveness of vaccines and the impact of imprudent reopening. Leveraging over two years of county-level COVID-19 data in the US, this study aims to investigate relationships among vaccination, human mobility, and COVID-19 health outcomes (assessed via case rate and case-fatality rate), controlling for socioeconomic, demographic, racial/ethnic, and partisan factors. A set of cross-sectional models was first fitted to empirically compare disparities in COVID-19 health outcomes before and during the Omicron surge. Then, time-varying mediation analyses were employed to delineate how the effects of vaccine and mobility on COVID-19 health outcomes vary over time. Results showed that vaccine effectiveness against case rate lost significance during the Omicron surge, while its effectiveness against case-fatality rate remained significant throughout the pandemic. We also documented salient structural inequalities in COVID-19-related outcomes, with disadvantaged populations consistently bearing a larger brunt of case and death tolls, regardless of high vaccination rates. Last, findings revealed that mobility presented a significantly positive relationship with case rates during each wave of variant outbreak. Mobility substantially mediated the direct effect from vaccination to case rate, leading to a 10.276 % (95 % CI: 6.257, 14.294) decrease in vaccine effectiveness on average. Altogether, our study implies that sole reliance on vaccination to halt COVID-19 needs to be re-examined. Well-resourced and coordinated efforts to enhance vaccine effectiveness, mitigate health disparity and selectively loosen non-pharmaceutical interventions are essential to bringing the pandemic to an end.

Health disparity in the spread of COVID-19: Evidence from social distancing, risk of interactions, and access to testing.

OBJECTIVE: - To identify and assess whether three major risk factors that due to differential access to flexible resources might help explain disparities in the spread of COVID-19 across communities with different socioeconomic status, including socioeconomic inequalities in social distancing, the potential risk of interpersonal interactions, and access to testing. METHODS: Analysis uses ZIP code level weekly COVID-19 new cases, weekly population movement flows, weekly close-contact index, and weekly COVID-19 testing sites in Southern California from March 2020 to April 2021, merged with the U.S. census data to measure ZIP code level socioeconomic status and cofounders. This study first develops the measures for social distancing, the potential risk of interactions, and access to testing. Then we employ a spatial lag regression model to quantify the contributions of those factors to weekly COVID-19 case growth. RESULTS: Results identify that, during the first COVID-19 wave, new case growth of the low-income group is two times higher than that of the high-income group. The COVID-19 case disparity widens to four times in the second COVID-19 wave. We also observed significant disparities in social distancing, the potential risk of interactions, and access to testing among communities with different socioeconomic status. In addition, all of them contribute to the disparities of COVID-19 incidences. Among them, the potential risk of interactions is the most important contributor, whereas testing accessibility contributes least. We also found that close-contact is a more effective measure of social distancing than population movements in examining the spread of COVID-19. CONCLUSION: - This study answers critically unaddressed questions about health disparities in the spread of COVID-19 by assessing factors that might explain why the spread is different in different groups.