Immune Activation: A Link Between Food Insecurity and Chronic Disease in People Living With Human Immunodeficiency Virus.

Persistent immune activation is a hallmark of human immunodeficiency virus (HIV) infection and thought to play a role on chronic diseases in people with HIV (PWH). Food insecurity is disproportionately prevalent in PWH and is associated with adverse health outcomes. We determined whether food insecurity was associated with increased plasma levels of soluble CD14, CD27, and CD163 in 323 antiretroviral-treated PWH from the Miami Adult Studies on HIV cohort. Nearly half (42.7%) of participants were food insecure, and 85.5% were virally suppressed (<200 copies/mL). Food insecurity was independently associated with higher levels of soluble CD14 and soluble CD27. Very low food security was associated with increased soluble CD163 levels among those with lower CD4+ cell counts. Food insecurity may promote immune activation in PWH, suggesting a biological link between food insecurity and chronic disease among PWH. Improving financial security and access to high-quality diets could reduce the burden of disease in this highly vulnerable population.

Disability and COVID-19: Challenges, testing, vaccination, and postponement and avoidance of medical care among minoritized communities.

BACKGROUND: People with disabilities face heightened vulnerability to COVID-19. OBJECTIVE: This study investigated (1) the relationships between disability and COVID-19-related challenges, testing, vaccination, and infection and (2) predictors of loss of healthcare coverage and postponement and avoidance of medical care during the pandemic. METHODS: This cross-sectional study was conducted in Miami, Florida, between March 2021 and February 2022 as part of the NIH Rapid Acceleration of Diagnostics-Underserved Populations initiative. Disability was defined using a standard measure that assesses six universal functions. Participants reported sociodemographic data, COVID-19 testing, infection history, challenges, and healthcare history. Vaccinations were confirmed with medical records and COVID-19 positivity was assessed using real-time reverse transcription-polymerase chain reaction. Statistical analyses included multivariable logistic regression. RESULTS: Among 1,689 participants with a median age of 57.0, 50.6% were male, and 48.9% were non-Hispanic Black. Disability was associated with greater odds of all assessed COVID-19 challenges: healthcare (aOR:1.60; 95% CI:1.23-2.07), housing (aOR:2.15; 95% CI:1.62-2.87), insufficient food (aOR:1.97; 95% CI:1.54-2.52), water scarcity (aOR:2.33; 95% CI:1.60-3.37), medications (aOR:2.04; 95% CI:1.51-2.77), and transportation (aOR:2.56; 95% CI:1.95-3.36). Those reporting employment disability were less likely to have received COVID-19 testing (81.1% vs. 85.3%, p = 0.026) or to have history of COVID-19 positivity (aOR:0.63; 95% CI:0.44-0.92). Disability predicted avoidance (aOR:2.76; 95% CI:1.95-3.91) and postponement (aOR: 2.24; 95% CI:1.72-2.91) of medical care. CONCLUSIONS: Disability is associated with higher odds of COVID-19 challenges and postponement and avoidance of medical care. Those reporting employment disability had a lower likelihood of COVID-19 testing. Public health responses to healthcare crises should prioritize the special challenges of people living with disabilities.

Drug use and COVID-19 testing, vaccination, and infection among underserved, minority communities in Miami, Florida.

The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately impacted people who use drugs (PWUD). This study explored relationships between drug use, COVID-19 testing, vaccination, and infection. This cross-sectional study was conducted in Miami, Florida between March 2021 and October 2022 as part of the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative and the Miami Adult Studies on HIV (MASH) cohort. Users of cannabis, cocaine/crack, heroin/fentanyl, methamphetamines, hallucinogens, and/or prescription drug misuse in the previous 12 months were considered PWUD. Sociodemographic data, COVID-19 testing history, and vaccination-related beliefs were self-reported. Vaccinations were confirmed with medical records and positivity was determined with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Statistical analyses included chi-square tests and logistic regression. Of 1,780 participants, median age was 57 years, 50.7% were male, 50.2% Non-Hispanic Black, and 66.0% reported an annual income less than $15,000. Nearly 28.0% used drugs. PWUD were less likely than non-users to self-report ever testing positive for SARS-CoV-2 (14.7% vs. 21.0%, p = 0.006). However, 2.6% of participants tested positive for SARS-CoV-2, with no significant differences between PWUD and non-users (3.7% vs. 2.2%, p = 0.076). PWUD were more likely than non-users to experience difficulties accessing testing (10.2% vs. 7.1%, p = 0.033), vaccine hesitancy (58.9% vs. 43.4%, p = 0.002) and had lower odds of receiving any dose of a COVID-19 vaccine compared to non-users (aOR, 0.63; 95% CI, 0.49-0.81; p<0.001). PWUD presented with greater difficulties accessing COVID-19 testing, greater vaccine hesitancy, and lower odds of vaccination. Testing and immunization plans that are tailored to the needs of PWUD and consider access, trust-building campaigns, and education may be needed.

Central and peripheral tau retention modulated by an anti-tau antibody.

Tau protein blood levels dependent on its distribution to peripheral organs and possible elimination from the body. Thus, the peripheral distribution of CSF-derived tau protein was explored, especially since there is a transition to blood-based biomarkers and the emerging idea that tau pathology may spread beyond brain. Near infrared fluorescence (NIRF) was mainly used to analyze tau (tau-NIRF) distribution after its intracisternal or intravenous injection. There was a striking uptake of blood- or CSF-derived tau-NIRF protein by the skeletal structures, liver, small intestine (duodenum), gall bladder, kidneys, urinary bladder, lymph nodes, heart, and spleen. In aging and in older APP/PS1 mice, tau uptake in regions, such as the brain, liver, and skeleton, was increased. In bone (femur) injected tau protein was associated with integrin-binding sialoprotein (IBSP), a major non-collagenous glycoprotein that is associated with mineralization. Tau-NIRF was cleared slowly from CSF via mainly across the cribriform plate, and cervical lymph nodes. In brain, some of the CSF injected tau protein was associated with NeuN-positive and PDGFRý-positive cells, which may explain its retention. The presence of tau in the bladders suggested excretion routes of tau. CSF anti-tau antibody increased CSF tau clearance, while blood anti-tau antibody decreased tau accumulation in the femur but not in liver, kidney, and spleen. Thus, the data show a body-wide distribution and retention of CSF-derived tau protein, which increased with aging and in older APP/PS1 mice. Further work is needed to elucidate the relevance of tau accumulation in each organ to tauopathy.

Diet Quality and Liver Health in People Living with HIV in the MASH Cohort: A Multi-Omic Analysis of the Fecal Microbiome and Metabolome.

The gut-liver axis has been recognized as a potential pathway in which dietary factors may contribute to liver disease in people living with HIV (PLWH). The objective of this study was to explore associations between dietary quality, the fecal microbiome, the metabolome, and liver health in PLWH from the Miami Adult Studies on HIV (MASH) cohort. We performed a cross-sectional analysis of 50 PLWH from the MASH cohort and utilized the USDA Healthy Eating Index (HEI)-2015 to measure diet quality. A Fibrosis-4 Index (FIB-4) score < 1.45 was used as a strong indication that advanced liver fibrosis was not present. Stool samples and fasting blood plasma samples were collected. Bacterial composition was characterized using 16S rRNA sequencing. Metabolomics in plasma were determined using gas and liquid chromatography/mass spectrometry. Statistical analyses included biomarker identification using linear discriminant analysis effect size. Compared to participants with FIB-4 ≥ 1.45, participants with FIB-4 < 1.45 had higher intake of dairy (p = 0.006). Fibrosis-4 Index score was inversely correlated with seafood and plant protein HEI component score (r = -0.320, p = 0.022). The relative abundances of butyrate-producing taxa Ruminococcaceae, Roseburia, and Lachnospiraceae were higher in participants with FIB-4 < 1.45. Participants with FIB-4 < 1.45 also had higher levels of caffeine (p = 0.045) and related metabolites such as trigonelline (p = 0.008) and 1-methylurate (p = 0.023). Dietary components appear to be associated with the fecal microbiome and metabolome, and liver health in PLWH. Future studies should investigate whether targeting specific dietary components may reduce liver-related morbidity and mortality in PLWH.

Unusual case of spinal subdural empyema with ventriculitis managed conservatively with lumbar drain.

It has long been believed that spinal subdural empyemas (SDEs) with neurological symptoms result in death if operative intervention is not performed. We present a case of addressing an extensive spinal SDE with a minimally invasive procedure: a bedside lumbar drain. Our patient is a 67-year-old man with medical history significant for type I diabetes who presented 2 weeks after a right shoulder steroid injection with septic arthritis. An MRI was obtained for back pain which revealed spinal SDE from the cervical to lumbosacral spine. Given patient's acute sepsis, haemodynamic instability, and extent of empyema, we placed a lumbar drain for decompression. The patient had a prolonged complicated hospital course. Imaging 2 months later revealed interval decrease in the spinal SDE. Although this severe septic event left the patient with significant deficits, he was able to return to ambulation without surgical intervention.

Stress Increases the Association between Cigarette Smoking and Mental Disorders, as Measured by the COVID-19-Related Worry Scale, in the Miami Adult Studies on HIV (MASH) Cohort during the Pandemic.

Background: Smoking has been associated with mental disorders (MD). People who smoke are at a higher risk of contracting COVID-19 and experiencing more severe symptoms of the illness. This study aimed to investigate the relationship between cigarette smoking and MD before and during the COVID-19 pandemic and whether it was influenced by COVID-19-related stress in the MASH cohort. Methods: An ambispective design was used with data collected during the pandemic (July/August 2020) by the COVID-19-Related Worry Scale, a parameter for stress, and data collected at the participants' last cohort visit before the pandemic (December 2019). Results: In our sample of 314 participants, 58.6% were living with HIV, 39.2% had MD, 52.5% smoked before, and 47.8% smoked during the pandemic. Participants with MD were twice as likely to smoke cigarettes both before (aOR = 2.02, 95% CI: 1.21−3.37, p = 0.007) and during the pandemic (aOR = 2.10, 95% CI: 1.24−3.56, p = 0.006); and experienced higher levels of stress measured by the COVID-19-Related Worry Scale (8.59 [5.0−10.0] vs. 7.65 [5.0−10.0]; p = 0.026) compared to those without MD. Participants with MD and high levels of stress smoked more days per month (20.1 [0−30] days) than those with lower levels of stress (9.2 [0−30] days, p = 0.021), and more than those with high levels of stress, but no MD (2.6 [0−30] days, p < 0.001). Conclusions: Cigarette smoking decreased in the MASH cohort during the pandemic, but increased in participants with MD and higher levels of stress.

Multiomic analysis reveals microbiome-related relationships between cocaine use and metabolites.

OBJECTIVE: Over 19 million individuals globally have a cocaine use disorder, a significant public health crisis. Cocaine has also been associated with a pro-inflammatory state and recently with imbalances in the intestinal microbiota as compared to nonuse. The objective of this pilot study was to characterize the gut microbiota and plasma metabolites in people with HIV (PWH) who use cocaine compared with those who do not. DESIGN: Cross-sectional study. METHODS: A pilot study in PWH was conducted on 25 cocaine users and 25 cocaine nonusers from the Miami Adult Studies on HIV cohort. Stool samples and blood plasma were collected. Bacterial composition was characterized using 16S rRNA sequencing. Metabolomics in plasma were determined using gas and liquid chromatography/mass spectrometry. RESULTS: The relative abundances of the Lachnopspira genus, Oscillospira genus, Bifidobacterium adolescentis species, and Euryarchaeota phylum were significantly higher in the cocaine- using PWH compared to cocaine-nonusing PWH. Cocaine-use was associated with higher levels of several metabolites: products of dopamine catabolism (3-methoxytyrosine and 3-methoxytyramine sulfate), phenylacetate, benzoate, butyrate, and butyrylglycine. CONCLUSIONS: Cocaine use was associated with higher abundances of taxa and metabolites known to be associated with pathogenic states that include gastrointestinal conditions. Understanding key intestinal bacterial functional pathways that are altered due to cocaine use in PWH will provide a better understanding of the relationships between the host intestinal microbiome and potentially provide novel treatments to improve health.

Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2.

While there is SARS-CoV-2 multiorgan tropism in severely infected COVID-19 patients, it's unclear if this occurs in healthy young individuals. In addition, for antibodies that target the spike protein (SP), it's unclear if these reduce SARS-CoV-2/SP multiorgan tropism equally. We used fluorescently labeled SP-NIRF to study viral behavior, using an in vivo dynamic imaging system and ex in vivo tissue analysis, in young mice. We found a SP body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. SP uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or CSF. Thus, the brain vascular barriers were effective in restricting the entry of SP into brain parenchyma in young healthy mice. While both anti-ACE2 and anti-SP antibodies suppressed SP biodistribution and organ uptake, anti-SP antibody was more effective. By extension, our data support the efficacy of these antibodies on SARS-CoV-2 multiorgan tropism, which could determine COVID-19 organ-specific outcomes.

COVID-19 Testing and the Impact of the Pandemic on the Miami Adult Studies on HIV Cohort.

BACKGROUND: Socioeconomic disadvantages and potential immunocompromise raise particular concerns for people living with HIV (PLWH) and other marginalized communities during the COVID-19 pandemic. In this study, we explored COVID-19 testing and the impact of the pandemic among participants from the Miami Adult Studies on HIV cohort, predominantly composed of low-income minorities living with and without HIV. METHODS: Between July and August 2020, a telephone survey was administered to 299 Miami Adult Studies on HIV participants to assess COVID-19 testing, prevention behaviors, and psychosocial stressors. Health care utilization, antiretroviral adherence, food insecurity, and substance use during the pandemic were compared with those of their last cohort visit (7.8 ± 2.9 months earlier). RESULTS: Half of surveyed participants had been tested for COVID-19, 8 had tested positive and 2 had been hospitalized. PLWH (n = 183) were 42% times less likely than HIV-uninfected participants to have been tested. However, after adjustment for age, employment, COVID-19 symptoms, mental health care, and substance use, the effect of HIV status was no longer significant. PLWH were more likely to have seen a health care provider, use face coverings, and avoid public transportation and less likely to be food insecure and drink hazardously. There were significant changes in substance use patterns during the pandemic when compared with those before. CONCLUSION: PLWH, compared with their HIV-uninfected peers, were more likely to engage in preventive measures and health care during the pandemic, potentially reducing their exposure to COVID-19. There were no reported changes in antiretroviral adherence or health care utilization, but there were changes in substance use; these need to be monitored as this crisis progresses.

Sex Differences, Cocaine Use, and Liver Fibrosis Among African Americans in the Miami Adult Studies on HIV Cohort.

Background: HIV infection disproportionally affects African Americans. Liver disease is a major cause of non-HIV morbidity and mortality in this population. Substance abuse accelerates HIV disease and may facilitate progression of liver disease. This study investigated the relationship between sex differences and cocaine use with liver injury, characterized as hepatic fibrosis. Materials and Methods: A cross-sectional study was conducted on 544 African Americans [369 people living with HIV (PLWH) and 175 HIV seronegative] from the Miami Adult Studies on HIV (MASH) cohort. Cocaine use was determined with a validated self-reported questionnaire and confirmed with urine screen. Fasting blood was used to estimate liver fibrosis using the noninvasive fibrosis-4 (FIB-4) index. Results: Men living with HIV had 1.79 times higher odds for liver fibrosis than women living with HIV (p = 0.038). African American women had higher CD4 count (p = 0.001) and lower HIV viral load (p = 0.011) compared to African American men. Fewer women (PLWH and HIV seronegative) smoked cigarettes (p = 0.002), and fewer had hazardous or harmful alcohol use (p < 0.001) than men. Women also had higher body mass index (kg/m2) (p < 0.001) compared to men. No significant association was noted among HIV seronegative participants for liver fibrosis by sex differences or cocaine use. Among African Americans living with HIV, cocaine users were 1.68 times more likely to have liver fibrosis than cocaine nonusers (p = 0.044). Conclusions: Sex differences and cocaine use appear to affect liver disease among African Americans living with HIV pointing to the importance of identifying at-risk individuals to improve outcomes of liver disease.