Curating the Evidence About COVID-19 for Frontline Public Health and Clinical Care: The Novel Coronavirus Research Compendium.

The public health crisis created by the COVID-19 pandemic has spurred a deluge of scientific research aimed at informing the public health and medical response to the pandemic. However, early in the pandemic, those working in frontline public health and clinical care had insufficient time to parse the rapidly evolving evidence and use it for decision-making. Academics in public health and medicine were well-placed to translate the evidence for use by frontline clinicians and public health practitioners. The Novel Coronavirus Research Compendium (NCRC), a group of >60 faculty and trainees across the United States, formed in March 2020 with the goal to quickly triage and review the large volume of preprints and peer-reviewed publications on SARS-CoV-2 and COVID-19 and summarize the most important, novel evidence to inform pandemic response. From April 6 through December 31, 2020, NCRC teams screened 54 192 peer-reviewed articles and preprints, of which 527 were selected for review and uploaded to the NCRC website for public consumption. Most articles were peer-reviewed publications (n = 395, 75.0%), published in 102 journals; 25.1% (n = 132) of articles reviewed were preprints. The NCRC is a successful model of how academics translate scientific knowledge for practitioners and help build capacity for this work among students. This approach could be used for health problems beyond COVID-19, but the effort is resource intensive and may not be sustainable in the long term.

Menopause Is Associated With Immune Activation in Women With HIV.

BACKGROUND: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown. METHODS: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1) were measured at 674 person-visits spanning ≤2 years. RESULTS: Menopause (post- vs premenopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (ß = 161.89 ng/mL; 95% confidence interval [CI], 18.37-305.41 and 65.48 ng/mL, 95% CI, 6.64-124.33, respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI, 16.63-484.79; P = .04), but not in premenopausal or postmenopausal periods. CONCLUSIONS: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during menopausal transition warrant further investigation.

Change in Circulating Undercarboxylated Osteocalcin (ucOCN) Is Associated With Fat Accumulation in HIV-Seropositive Women.

BACKGROUND: Bone mineral density loss and fat accumulation are common in people living with HIV. The bone-derived hormone, undercarboxylated osteocalcin (ucOCN) regulates fat metabolism. We investigated the relationship between ucOCN change and body fat change among perimenopausal/postmenopausal HIV-seronegative and HIV-seropositive women on long-term antiretrovirals. METHODS: Perimenopausal and postmenopausal women enrolled in the Women's Interagency HIV Study MSK substudy underwent trunk and total fat assessment by dual energy x-ray absorptiometry (DXA) at study enrollment (index visit) and again 2 years later. Circulating ucOCN and cOCN were also measured at the index and 2-year visits. The correlation between the 2-year change in ucOCN and cOCN and change in trunk and total fat was assessed as a function of HIV serostatus using linear regression modeling. Multivariate linear regression assessed the association between ucOCN and cOCN change and total and trunk fat change after adjusting for sociodemographic variables. Linear regression models restricted to HIV-seropositive women were performed to examine the contributions of HIV-specific factors (index CD4 count, viral load, and combined antiretroviral therapy use) on the associations. RESULTS: Increased ucOCN over the 2-year follow-up was associated with less trunk and total fat accumulation in models adjusting for HIV serostatus and participants sociodemographics, whereas there was no association with cOCN and the fat parameters. None of the HIV-specific factors evaluated influenced the association between ucOCN and fat parameters. CONCLUSION: The current study suggests that increases in ucOCN are associated with decreased fat accumulation in HIV-seronegative and HIV-seropositive postmenopausal women on long-term antiretroviral therapy.

Marijuana use and pneumonia risk in a cohort of HIV-infected and HIV-uninfected men.

BACKGROUND: The prevalence of marijuana use is increasing in the United States. Marijuana smoking has been shown to impair the microbicidal activity of alveolar macrophages and decrease the number of ciliated epithelial cells in the bronchi with a parallel increase in the number of mucus-secreting surface epithelial cells, which may increase the risk of pneumonia. However, it remains unclear whether there is an association between smoking marijuana and pneumonia. METHODS: Using data from the Multicenter AIDS Cohort Study (MACS), a long-term observational cohort study of men who have sex with men in the United States, we used Cox proportional hazards models to estimate the risk of pneumonia among HIV-infected (n = 2784) and HIV-uninfected (n = 2665) men from 1984 to 2013, adjusted for time-varying and fixed baseline covariates. RESULTS: Weekly or daily marijuana use was not significantly associated with increased risk of pneumonia among HIV-uninfected men (adjusted hazard ratio; 95% confidence limits: 0.83, 0.56-1.23). In the disaggregated dose-response analysis, daily use (0.68, 0.34-1.35) was associated with a lower point estimate than weekly use [0.99, 0.79-1.25]. CONCLUSION: Marijuana smoking was not associated with a significant increase in risk of pneumonia among HIV-infected or HIV-uninfected men.

The projected impact of geographic targeting of oral cholera vaccination in sub-Saharan Africa: A modeling study.

BACKGROUND: Cholera causes an estimated 100,000 deaths annually worldwide, with the majority of burden reported in sub-Saharan Africa. In May 2018, the World Health Assembly committed to reducing worldwide cholera deaths by 90% by 2030. Oral cholera vaccine (OCV) plays a key role in reducing the near-term risk of cholera, although global supplies are limited. Characterizing the potential impact and cost-effectiveness of mass OCV deployment strategies is critical for setting expectations and developing cholera control plans that maximize the chances of success. METHODS AND FINDINGS: We compared the projected impacts of vaccination campaigns across sub-Saharan Africa from 2018 through 2030 when targeting geographically according to historical cholera burden and risk factors. We assessed the number of averted cases, deaths, and disability-adjusted life years and the cost-effectiveness of these campaigns with models that accounted for direct and indirect vaccine effects and population projections over time. Under current vaccine supply projections, an approach optimized to targeting by historical burden is projected to avert 828,971 (95% CI 803,370-859,980) cases (equivalent to 34.0% of projected cases; 95% CI 33.2%-34.8%). An approach that balances logistical feasibility with targeting historical burden is projected to avert 617,424 (95% CI 599,150-643,891) cases. In contrast, approaches optimized for targeting locations with limited access to water and sanitation are projected to avert 273,939 (95% CI 270,319-277,002) and 109,817 (95% CI 103,735-114,110) cases, respectively. We find that the most logistically feasible targeting strategy costs US$1,843 (95% CI 1,328-14,312) per DALY averted during this period and that effective geographic targeting of OCV campaigns can have a greater impact on cost-effectiveness than improvements to vaccine efficacy and moderate increases in coverage. Although our modeling approach does not project annual changes in baseline cholera risk or directly incorporate immunity from natural cholera infection, our estimates of the relative performance of different vaccination strategies should be robust to these factors. CONCLUSIONS: Our study suggests that geographic targeting substantially improves the cost-effectiveness and impact of oral cholera vaccination campaigns. Districts with the poorest access to improved water and sanitation are not the same as districts with the greatest historical cholera incidence. While OCV campaigns can improve cholera control in the near term, without rapid progress in developing water and sanitation services or dramatic increases in OCV supply, our results suggest that vaccine use alone is unlikely to allow us to achieve the 2030 goal.

Inflammatory biomarkers and subclinical carotid atherosclerosis in HIV-infected and HIV-uninfected men in the Multicenter AIDS Cohort Study.

BACKGROUND: HIV-infected persons have an increased risk of atherosclerosis relative to uninfected individuals. Inflammatory processes may contribute to this risk. We evaluated the associations of 10 biomarkers of systemic inflammation (CRP, IL-6, sTNF-αR1 and 2), monocyte activation (CCL2, sCD163, sCD14), coagulation (fibrinogen, D-dimer), and endothelial dysfunction (ICAM-1) with subclinical carotid atherosclerosis among participants in the Multicenter AIDS Cohort Study (MACS). METHODS: Carotid plaque and intima media thickness (IMT) in the common carotid (CCA-IMT) and bifurcation region were assessed by B mode ultrasound among 452 HIV-infected and 276 HIV-uninfected men from 2010-2013. Associations between levels of each biomarker and presence of focal plaque and IMT were assessed by logistic and linear regression models, adjusting for demographics, risk behaviors, traditional cardiovascular disease (CVD) risk factors, and HIV disease characteristics. RESULTS: Compared to HIV-uninfected men, HIV-infected men had significantly higher levels of 8 of the 10 biomarkers. Overall, men with sCD163, CCL2, IL-6, and CRP levels in the highest quintile had approximately 2 times the odds of carotid plaque relative to those with levels in the lowest quintile, independent of demographic and CVD risk factors. Fibrinogen levels were positively associated with CCA-IMT while ICAM-1, CCL2, and sTNF-αR1 levels were positively associated with bifurcation-IMT. Among HIV-uninfected men, higher levels of sTNF-αR2 were positively associated with CCA-IMT, fibrinogen with bifurcation-IMT and carotid plaque, and ICAM-1 with carotid plaque. CONCLUSION: In addition to greater levels of systemic inflammation, heightened monocyte activation (sCD163, CCL2) may contribute to the burden of atherosclerosis among HIV-infected persons.

Mapping the burden of cholera in sub-Saharan Africa and implications for control: an analysis of data across geographical scales.

BACKGROUND: Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions. METHODS: We combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 km × 20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence. FINDINGS: We included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141 918 cholera cases (95% credible interval [CrI] 141 538-146 505) were reported per year. 4·0% (95% CrI 1·7-16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region's cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population. INTERPRETATION: Although cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas could substantially increase the efficiency of cholera control programmes. FUNDING: The Bill & Melinda Gates Foundation.

What is a Hotspot Anyway?

AbstractThe importance of spatial clusters, or "hotspots," in infectious disease epidemiology has been increasingly recognized, and targeting hotspots is often seen as an important component of disease-control strategies. However, the precise meaning of "hotspot" varies widely in current research and policy documents. Hotspots have been variously described as areas of elevated incidence or prevalence, higher transmission efficiency or risk, or higher probability of disease emergence. This ambiguity has led to confusion and may result in mistaken inferences regarding the best way to target interventions. We surveyed the literature on epidemiologic hotspots, examining the multitude of ways in which the term is used; and highlight the difference in the geographic scale of hotspots and the properties they are supposed to have. In response to the diversity in the term's usage, we advocate the use of more precise terms, such as "burden hotspot," "transmission hotspot," and "emergence hotspot," as well as explicit specification of the spatiotemporal scale of interest. Increased precision in terminology is needed to ensure clear and effective policies for disease control.

Multiplex assay reliability and long-term intra-individual variation of serologic inflammatory biomarkers.

BACKGROUND: Circulating cytokines, chemokines, and soluble cytokine receptors can serve as biomarkers of inflammation and immune dysregulation. Good reliability of multiplex platforms, which allow for simultaneous, comprehensive biomarker assessment, is critical for their utility in epidemiologic studies. We examined the reliability of the Meso-Scale Discovery (MSD) platform to simultaneously quantitate 15 cytokines and chemokines and the Luminex platform (R&D Systems) to quantitate 5 soluble receptors and 2 chemokines and cytokines and evaluated long-term within-person correlation of these biomarkers. METHODS: The detectability and reliability of these assay systems were assessed using the same external controls across plates and archived sera from 250 HIV- men in the Multicenter AIDS Cohort Study. Using up to four visits per person from 1984 to 2009, age-adjusted intraclass correlation coefficients (ICC) of biomarkers with >80% detectability (CCL11, CXCL8, CXCL10, CCL2, CCL4, CCL13, CCL17, CXCL13, IL-10, IL-12p70, IL-6, TNF-α, BAFF, sCD14, sCD27, sgp130, sIL-2Rα, and sTNF-R2) were obtained using linear mixed models. RESULTS: Most biomarkers were detectable in 80% of control samples; IFN-γ, GM-CSF, and IL-2 were undetectable in >20% of samples. Among the HIV-uninfected men, most biomarkers showed fair to strong within-person correlation (ICC>0.40) up to 15years. The ICC for CXCL8 was good in the short term but decreased with increasing time between visits, becoming lower (ICC<0.40) after 8years. CONCLUSIONS: These multiplexed assays showed acceptable reliability for use in epidemiologic research, despite some technical variability and limitations in cytokine quantitation. Most biomarkers displayed moderate-to-excellent intra-individual variability over the long term, suggesting their utility in prospective studies investigating etiologic associations with diverse chronic conditions.

Data on serologic inflammatory biomarkers assessed using multiplex assays and host characteristics in the Multicenter AIDS Cohort Study (MACS).

This article contains data on the associations between fixed and modifiable host characteristics and twenty-three biomarkers of inflammation and immune activation measured longitudinally in a cohort of 250 HIV-uninfected men from the Multicenter AIDS Cohort Study (1984-2009) after adjusting for age, study site, and blood draw time of day using generalized gamma regression. This article also presents associations between each biomarker and each host characteristic in a sample restricted to 2001-2009. These data are supplemental to our original research article entitled "Host factors associated with serologic inflammatory markers assessed using multiplex assays" (McKay, S. Heather, Bream, H. Jay, Margolick, B. Joseph, Martínez-Maza, Otoniel, Phair, P. John, Rinaldo, R. Charles, Abraham, G. Alison, L.P. Jacobson, 2016) [1].

Host factors associated with serologic inflammatory markers assessed using multiplex assays.

Chronic systemic inflammation contributes to the development of adverse health conditions, yet the influence of fixed and modifiable risk factors on many serologic biomarkers of inflammation remains largely unknown. Serum concentrations of twenty-three biomarkers, including C-reactive protein (CRP), cytokines (CXCL11, CXCL8, CXCL10, CCL2, CCL13, CCL4, CCL17, CXCL13, IL-10, IL-12p70, IL-6, TNF-α, IL-2, IFN-γ, IL-1ß, GM-CSF, BAFF), and soluble immune receptors (sCD14, sIL-2Rα, sCD27, sgp130, sTNF-R2) were measured longitudinally using multiplexed immunometric assays in 250 HIV-uninfected men followed in the Multicenter AIDS Cohort Study (1984-2009). Generalized gamma regression was used to determine the statistical significance of factors associated with each biomarker. After accounting for age, race, and education, and for analysis of multiple biomarkers, higher concentrations of specific individual biomarkers were significantly (P<0.002) associated with hypertension, obesity, hepatitis C infection, stimulant use, and diabetes and lower concentrations with hypercholesterolemia. These associations should be taken into account in epidemiological studies of these biomarkers, and may provide potential targets for disease prevention and treatment.

Smoking-cessation interventions for U.S. young adults: a systematic review.

CONTEXT: Studies have demonstrated the importance of quitting smoking before age 30 years to avoid tobacco-related mortality but little attention has been paid to developing evidence-based smoking-cessation interventions for young adults, as distinct from adolescents and older-aged adults. The objective of this study was to conduct a systematic review of smoking-cessation interventions for U.S. young adults (aged 18-24 years). EVIDENCE ACQUISITION: Electronic searches were conducted in CINAHL, the Cochrane Library, EMBASE, PsycINFO, PubMed, Scopus, and Sociological Abstracts to identify eligible interventions through August 31, 2009. Two independent coders critically evaluated the methodology and findings of all retrieved articles. Data analysis was conducted in 2010. EVIDENCE SYNTHESIS: Twelve RCTs and two nonrandomized studies met the inclusion criteria; these studies varied with respect to sample size, intervention, outcomes assessed, and smoking measures. Pooled results for two studies based on social cognitive theory indicated that they were effective in promoting short-term abstinence at 1-3-month follow-up and 4-6-month follow-up. Four studies had a significant positive impact on smoking cessation: two in the short term and two at 6 months or more. CONCLUSIONS: There is limited evidence demonstrating efficacy of smoking-cessation interventions for U.S. young adults. There were no pharmacologic interventions included in this review. Promising interventions were brief, with extended support via telephone and electronic media. Further high-quality studies using standardized smoking measures and additional studies outside the college setting are needed to identify and tailor effective smoking-cessation interventions for at-risk young adults in the U.S.