Nucleocapsid and Spike Protein-Based Anti-SARS-CoV-2 Assay Performance in the Minority and Rural Coronavirus Insights Study: Characteristics of Socioeconomically Disadvantaged Populations with Health Disparities.

BACKGROUND: COVID-19 has had a devastating impact on Black, Hispanic, and other underserved, disadvantaged populations. Here anti-SARS-CoV-2 tests are characterized in disadvantaged patients to examine equivalence in US populations. METHODS: Underserved participant adults (age > 18 years) were enrolled before the availability of SARS-CoV-2 vaccines in Federal Qualified Health Centers in California, Florida, Louisiana, Illinois, and Ohio and contributed samples to the Minority and Rural Coronavirus Insights Study (MRCIS). A subset coined the MRCIS SARS-CoV-2 Antibody Cohort of 2365 participants was tested with the Roche Anti-SARS-CoV-2 assay (Cobas e601). Five hundred ninety-five of these were also tested with the Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG assay (VITROS-5600); 1770 were also tested with the Abbott ARCHITECT SARS-CoV-2 IgG assay (ARCHITECT-2000). Assay-specific cutoffs classified negative/positive results. RESULTS: Eight point four percent (199/2365) of the MRCIS SARS-CoV-2 Antibody Cohort was SARS-CoV-2 RNA positive at enrollment. Agreement between the Ortho/Roche and the Abbott/Roche antibody testing did not vary by enrollment RNA status. The Ortho (anti-spike protein) vs Roche (anti-nucleocapsid protein) comparison agreed substantially: kappa = 0.63 (95% CI: 0.57-0.69); overall agreement, 83%. However, agreement was even better for the Abbott vs Roche assays (both anti-nucleocapsid protein tests): kappa = 0.85 (95% CI: 0.81-0.87); overall agreement, 95%. Anti-SARS-CoV-2 comparisons stratified by demographic criteria demonstrated no significant variability in agreement by sex, race/ethnicity, or age. CONCLUSIONS: Analytical agreement is 96.4% for anti-spike-protein vs anti-nucleocapsid-protein comparisons. Physiologically, seroreversion of anti-nucleocapsid reactivity after infection occurred in the disadvantaged population similarly to general populations. No anti-SARS-CoV-2 assays included demonstrated a clinically significant difference due to the demographics of the disadvantaged MRCIS SARS-CoV-2 Antibody Cohort.

Vitamin D Levels and SARS-CoV-2 Infection among Medically Underserved Populations in the Minority and Rural Coronavirus Insights Study.

BACKGROUND: Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population of medically underserved persons presenting at five Federally qualified health centers in the United States. METHODS: We conducted a descriptive analysis to explore the relationship between vitamin D levels and SARS-CoV-2 infection among medically underserved participants. A combined molecular and serologic assessment was used to determine the prevalence of SARS-CoV-2 infection. Vitamin D was examined as both a categorical (vitamin D status: deficient, insufficient, optimal) and continuous (vitamin D level) variable. Chi-squared testing, polynomial regression models, and logistic regression models were used to assess the relationship between vitamin D and SARS-CoV-2 infection. RESULTS: The overall SARS-CoV-2 infection rate among participants was 25.9%. Most participants were either vitamin D deficient (46.5%) or insufficient (29.7%), and 23.8% had an optimal level. Vitamin D status was significantly associated with key SARS-CoV-2 infection risk factors. As mean vitamin D levels increased, the proportion of participants with SARS-CoV-2 infection decreased. For every 10 ng/mL increase in vitamin D levels the odds of SARS-CoV-2 infection decreased by 12% when adjusting for race/ethnicity and age (main effect model). Participants who identified as Hispanic/Latino or Black non-Hispanic had approximately two times increased odds of SARS-CoV-2 infection when adjusting for age and vitamin D levels compared to white non-Hispanics. However, when additional factors were added to the main effect model, the relationship between vitamin D levels and SARS-CoV-2 infection did not remain significant. CONCLUSION: Vitamin D levels were associated with an increased risk of SARS-CoV-2 infection. Hispanic/Latino and Black, non-Hispanic compared to White, non-Hispanic participants were at increased odds for infection, after adjusting for race/ethnicity and age.

Protein-truncating variant in APOL3 increases chronic kidney disease risk in epistasis with APOL1 risk alleles.

BACKGROUNDTwo coding alleles within the APOL1 gene, G1 and G2, found almost exclusively in individuals genetically similar to West African populations, contribute substantially to the pathogenesis of chronic kidney disease (CKD). The APOL gene cluster on chromosome 22 contains a total of 6 APOL genes that have arisen as a result of gene duplication.METHODSUsing a genome-first approach in the Penn Medicine BioBank, we identified 62 protein-altering variants in the 6 APOL genes with a minor allele frequency of >0.1% in a population of participants genetically similar to African reference populations and performed population-specific phenome-wide association studies.RESULTSWe identified rs1108978, a stop-gain variant in APOL3 (p.Q58*), to be significantly associated with increased CKD risk, even after conditioning on APOL1 G1/G2 carrier status. These findings were replicated in the Veterans Affairs Million Veteran Program and the All of Us Research Program. APOL3 p.Q58* was also significantly associated with a number of quantitative traits linked to CKD, including decreased kidney volume. This truncating variant contributed the most risk for CKD in patients monoallelic for APOL1 G1/G2, suggesting an epistatic interaction and a potential protective effect of wild-type APOL3 against APOL1-induced kidney disease.CONCLUSIONThis study demonstrates the utility of targeting population-specific variants in a genome-first approach, even in the context of well-studied gene-disease relationships.FUNDINGNational Heart, Lung, and Blood Institute (F30HL172382, R01HL169378, R01HL169458), Doris Duke Foundation (grant 2023-2024), National Institute of Biomedical Imaging and Bioengineering (P41EB029460), and National Center for Advancing Translational Sciences (UL1-TR-001878).

Advancing genomics to improve health equity.

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine.

The Minority and Rural Coronavirus Insights Study: Design and Baseline Characteristics of a Minority Cohort.

The Minority and Rural Coronavirus Insights Study (MRCIS) is an ongoing prospective cohort study examining health disparities associated with SARS-CoV-2 infection among medically underserved populations. This report describes procedures implemented to establish the MRCIS cohort and examines the factors associated with the molecular and serological assessment of SARS-CoV-2 infection status at participant enrollment. Participants were recruited from 5 geographically dispersed federally qualified health centers between November 2020 and April 2021. At baseline, participants completed a detailed demographic survey and biological samples were collected for testing. SARS-CoV-2 infection status was determined based on the combined molecular and serological test results. Chi-squared and logistic regression analyses were conducted to examine associations between sociodemographic factors, COVID-19 safety measures, existing comorbidities, and SARS-CoV-2 infection status. The final cohort included 3238 participants. The mean age of participants was 50.2 ± 15.8 years. Most participants identified as female (60.0%), heterosexual or straight (93.0%), White (47.6%), and Hispanic or Latino (49.1%). Approximately 26.1% of participants had at least one positive SARS-CoV-2 test result. The main effect model included age, sex, and race/ethnicity. Compared with adults ≥65 years, participants in all other age groups had ∼2 times increased odds of a positive SARS-CoV-2 test result. In addition, racial/ethnic minorities had ∼2 times increased odds of a positive SARS-CoV-2 infection status compared with non-Hispanic Whites. A unique cohort of a traditionally medically underserved minority population was established. Significant racial and ethnic disparities in SARS-CoV-2 infection status at baseline were discovered.

Demographic Determinants and Geographical Variability of COVID-19 Vaccine Hesitancy in Underserved Communities: Cross-sectional Study.

BACKGROUND: COVID-19 hospitalizations and deaths disproportionately affect underserved and minority populations, emphasizing that vaccine hesitancy can be an especially important public health risk factor in these populations. OBJECTIVE: This study aims to characterize COVID-19 vaccine hesitancy in underserved diverse populations. METHODS: The Minority and Rural Coronavirus Insights Study (MRCIS) recruited a convenience sample of adults (age≥18, N=3735) from federally qualified health centers (FQHCs) in California, the Midwest (Illinois/Ohio), Florida, and Louisiana and collected baseline data in November 2020-April 2021. Vaccine hesitancy status was defined as a response of "no" or "undecided" to the question "Would you get a coronavirus vaccine if it was available?" ("yes" categorized as not hesitant). Cross-sectional descriptive analyses and logistic regression models examined vaccine hesitancy prevalence by age, gender, race/ethnicity, and geography. The expected vaccine hesitancy estimates for the general population were calculated for the study counties using published county-level data. Crude associations with demographic characteristics within each region were assessed using the chi-square test. The main effect model included age, gender, race/ethnicity, and geographical region to estimate adjusted odds ratios (ORs) and 95% CIs. Interactions between geography and each demographic characteristic were evaluated in separate models. RESULTS: The strongest vaccine hesitancy variability was by geographic region: California, 27.8% (range 25.0%-30.6%); the Midwest, 31.4% (range 27.3%-35.4%); Louisiana, 59.1% (range 56.1%-62.1%); and Florida, 67.3% (range 64.3%-70.2%). The expected estimates for the general population were lower: 9.7% (California), 15.3% (Midwest), 18.2% (Florida), and 27.0% (Louisiana). The demographic patterns also varied by geography. An inverted U-shaped age pattern was found, with the highest prevalence among ages 25-34 years in Florida (n=88, 80.0%,) and Louisiana (n=54, 79.4%; P<.05). Females were more hesitant than males in the Midwest (n= 110, 36.4% vs n= 48, 23.5%), Florida (n=458, 71.6% vs n=195, 59.3%), and Louisiana (n= 425, 66.5% vs. n=172, 46.5%; P<.05). Racial/ethnic differences were found in California, with the highest prevalence among non-Hispanic Black participants (n=86, 45.5%), and in Florida, with the highest among Hispanic (n=567, 69.3%) participants (P<.05), but not in the Midwest and Louisiana. The main effect model confirmed the U-shaped association with age: strongest association with age 25-34 years (OR 2.29, 95% CI 1.74-3.01). Statistical interactions of gender and race/ethnicity with the region were significant, following the pattern found by the crude analysis. Compared to males in California, the associations with the female gender were strongest in Florida (OR=7.88, 95% CI 5.96-10.41) and Louisiana (OR=6.09, 95% CI 4.55-8.14). Compared to non-Hispanic White participants in California, the strongest associations were found with being Hispanic in Florida (OR=11.18, 95% CI 7.01-17.85) and Black in Louisiana (OR=8.94, 95% CI 5.53-14.47). However, the strongest race/ethnicity variability was observed within California and Florida: the ORs varied 4.6- and 2-fold between racial/ethnic groups in these regions, respectively. CONCLUSIONS: These findings highlight the role of local contextual factors in driving vaccine hesitancy and its demographic patterns.

Association of Racial/Ethnic Categories With the Ability of Genetic Tests to Detect a Cause of Cardiomyopathy.

Importance: Individuals of all races/ethnicities have a fundamental right to access health care and benefit from advances in science and medicine, including genetic testing. Objective: To determine whether detection rates for cardiomyopathy genetic testing differed between white people, Asian people, and underrepresented minorities (individuals of black, Hispanic, Native American, Alaskan Native, or Pacific Islander descent). Design, Setting, and Participants: We conducted a cross-sectional analysis of the genetic panel test results of 5729 probands who had a suspected diagnosis or family history of cardiomyopathy and who had been referred for testing between October 2003 and December 2017. Testing was performed at the Laboratory for Molecular Medicine at Partners Personalized Medicine in Cambridge, Massachusetts. Results were stratified into 3 categories of self-reported race/ethnicity: white, Asian, and underrepresented minorities. Main Outcomes and Measures: The primary outcome was whether a pathogenic or likely pathogenic variant was identified that explained the features or family history of cardiomyopathy. A secondary outcome was the number of test results that were inconclusive because of the presence of 1 or more variants of uncertain significance in the absence of an explanation for cardiomyopathy features or family history. Results: A total of 5729 probands were studied (of whom 3523 [61.5%] were male). Of these, 4539 (79.2%) were white, 348 (6.1%) were Asian individuals, and 842 (14.7%) were underrepresented minorities. Positive detection occurred in 1314 white individuals (29.0%) compared with 155 underrepresented minorities (18.4%; χ21 = 39.8; P < .001) and 87 Asian individuals (25.0%; χ21 = 2.5; P = .12). Inconclusive results were found in 1115 white individuals (24.6%) compared with 335 underrepresented minorities (39.8%; χ21 = 83.6; P < .001) and 136 Asian individuals (39.2%; χ21 = 35.8; P < .001). Conclusions and Relevance: These results show a significantly higher positive detection rate and a significantly lower rate of inconclusive results in white individuals in comparison with underrepresented minorities. This suggests greater clinical usefulness of genetic testing for cardiomyopathy in white persons in comparison with people of other racial/ethnic groups. This clear disparity warrants further study to understand the gaps in usefulness, which may derive from a lack of clinical testing and research in underrepresented minority populations, in the hopes of improving genetic testing outcomes for cardiomyopathy in nonwhite groups.

Lack Of Diversity In Genomic Databases Is A Barrier To Translating Precision Medicine Research Into Practice.

Precision medicine is predicted to revolutionize the clinical practice of medicine, in part by using molecular biomarkers to assess patients' risk, prognosis, and therapeutic response more precisely. However, reliance on biomarkers could present challenges for diverse populations that are not equitably represented in precision medicine research. We examined the populations included in genomic studies whose data were available in the following two public databases: the Genome-Wide Association Study Catalog and the database of Genotypes and Phenotypes. We found significantly fewer studies of African, Latin American, and Asian ancestral populations in comparison to European populations. These patterns were consistent across both data types and disease areas. While the number of genomic research studies that include non-European populations is modestly improving, the overall numbers are still low, and decisive action is needed now to implement the changes necessary for realizing the promise of precision medicine for all.