Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
Science ; 374(6571): 1127-1133, 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1723460

ABSTRACT

Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis-expression quantitative trait loci that are differentiated by genetic ancestry. Furthermore, genetic ancestry­associated genes are enriched among genes correlated with COVID-19 disease severity, suggesting that the early immune response contributes to ancestry-associated differences for multiple viral infection outcomes.


Subject(s)
African Americans/genetics , COVID-19/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza, Human/genetics , Influenza, Human/immunology , Leukocytes, Mononuclear/virology , /genetics , Adult , Aged , COVID-19/immunology , COVID-19/physiopathology , Disease Susceptibility , Gene Expression Regulation , Genetic Variation , Humans , Influenza A Virus, H1N1 Subtype/physiology , Interferon Type I/immunology , Interferon Type I/metabolism , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Quantitative Trait Loci , Severity of Illness Index , Single-Cell Analysis , Transcription, Genetic , Viral Load , Young Adult
2.
JAMA Intern Med ; 182(4): 386-395, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1653126

ABSTRACT

IMPORTANCE: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates. OBJECTIVE: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease. We tested the hypothesis that the APOL1 high-risk group is associated with a higher-risk of COVID-19-associated AKI and death. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 990 participants with African ancestry enrolled in the Million Veteran Program who were hospitalized with COVID-19 between March 2020 and January 2021 with available genetic information. EXPOSURES: The primary exposure was having 2 APOL1 risk variants (RV) (APOL1 high-risk group), compared with having 1 or 0 risk variants (APOL1 low-risk group). MAIN OUTCOMES AND MEASURES: The primary outcome was AKI. The secondary outcomes were stages of AKI severity and death. Multivariable logistic regression analyses adjusted for preexisting comorbidities, medications, and inpatient AKI risk factors; 10 principal components of ancestry were performed to study these associations. We performed a subgroup analysis in individuals with normal kidney function prior to hospitalization (estimated glomerular filtration rate ≥60 mL/min/1.73 m2). RESULTS: Of the 990 participants with African ancestry, 905 (91.4%) were male with a median (IQR) age of 68 (60-73) years. Overall, 392 (39.6%) patients developed AKI, 141 (14%) developed stages 2 or 3 AKI, 28 (3%) required dialysis, and 122 (12.3%) died. One hundred twenty-five (12.6%) of the participants were in the APOL1 high-risk group. Patients categorized as APOL1 high-risk group had significantly higher odds of AKI (adjusted odds ratio [OR], 1.95; 95% CI, 1.27-3.02; P = .002), higher AKI severity stages (OR, 2.03; 95% CI, 1.37-2.99; P < .001), and death (OR, 2.15; 95% CI, 1.22-3.72; P = .007). The association with AKI persisted in the subgroup with normal kidney function (OR, 1.93; 95% CI, 1.15-3.26; P = .01). Data analysis was conducted between February 2021 and April 2021. CONCLUSIONS AND RELEVANCE: In this cohort study of veterans with African ancestry hospitalized with COVID-19 infection, APOL1 kidney risk variants were associated with higher odds of AKI, AKI severity, and death, even among individuals with prior normal kidney function.


Subject(s)
Acute Kidney Injury , COVID-19 , Veterans , Acute Kidney Injury/genetics , African Americans/genetics , Aged , Apolipoprotein L1/genetics , Cohort Studies , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
4.
Genes (Basel) ; 12(12)2021 11 30.
Article in English | MEDLINE | ID: covidwho-1596962

ABSTRACT

Copy number variants (CNVs) provide numerous genetic differences between individuals, and they have been linked with multiple human diseases. Obesity is one of the highly heritable complex disorders, which is associated with copy number variance (CNV). A recent report shows that the 11q11 gene, a novel olfactory receptor, and its copy number variants are involved in the early onset of obesity. In the current study, we analyzed the 11q11 gene copy number variance (CNV) based on gender in White/European American (EA) and African American (AA) normal weight and overweight/obese children. Sixty-nine boys and fifty-eight girls between the ages of 6 and 10 years belonging to either EA or AA ethnicity were involved in this study. As per World Health Organization (WHO) guidelines, each participant's body weight and height were recorded. DNA was extracted from saliva, and the copy number variants for the 11q11 gene were measured using digital PCR. The descriptive analysis of the 11q11 copy number showed significantly more copies in girls compared to boys; similarly, AA participants had significantly increased CNV compared to EA. The normal weight (NW) and overweight/obese (OW/OB) girls were significantly less likely to belong to the low copy number variant (LCNV) group of 11q11 compared to boys; similarly, NW and OW/OB AA children were significantly less likely to belong to the LCNV group. The AA girls in LCNV had significantly higher BMI z-scores. Our findings suggest that the 11q11 copy number in children is race and gender-specific.


Subject(s)
African Americans/genetics , Body Weight/genetics , Chromosomes, Human, Pair 11 , Pediatric Obesity/genetics , Child , DNA Copy Number Variations , Female , Humans , Male , Receptors, Odorant/genetics , Saliva , Sex Characteristics , /genetics
5.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1428994

ABSTRACT

The 2020 US mortality totaled 2.8 million after early March, which is 17.3% higher than age-population-weighted mortality over the same time interval in 2017 to 2019, for a total excess death count of 413,592. We use data on weekly death counts by cause, as well as life tables, to quantify excess mortality and life years lost from both COVID-19 and non-COVID-19 causes by race/ethnicity, age, and gender/sex. Excess mortality from non-COVID-19 causes is substantial and much more heavily concentrated among males and minorities, especially Black, non-Hispanic males, than COVID-19 deaths. Thirty-four percent of the excess life years lost for males is from non-COVID-19 causes. While minorities represent 36% of COVID-19 deaths, they represent 70% of non-COVID-19 related excess deaths and 58% of non-COVID-19 excess life years lost. Black, non-Hispanic males represent only 6.9% of the population, but they are responsible for 8.9% of COVID-19 deaths and 28% of 2020 excess deaths from non-COVID-19 causes. For this group, nearly half of the excess life years lost in 2020 are due to non-COVID-19 causes.


Subject(s)
COVID-19/mortality , Cause of Death , Health Status Disparities , Minority Groups , Adolescent , Adult , African Americans/genetics , Age Factors , Aged , Aged, 80 and over , COVID-19/genetics , COVID-19/virology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , SARS-CoV-2/pathogenicity , Sex Characteristics , United States/epidemiology , Young Adult
6.
Hum Immunol ; 82(10): 713-718, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1322117

ABSTRACT

A disproportionate incidence of death has occurred in African Americans (Blacks) in the United States due to COVID-19. The reason for this disparity is likely to be multi-factorial and may involve genetic predisposition. The association of human leukocyte antigens (HLA) with severe COVID-19 was examined in a hospitalized population (89% Black, n = 36) and compared to HLA typed non-hospitalized individuals (20% Black, n = 40) who had recovered from mild disease. For additional comparison, HLA typing data was available from kidney transplant recipients and deceased donors. Hospitalized patients were followed for 45 days after admission to our medical center with death as the primary end-point. One HLA allele, B53, appeared to be more prevalent in the hospitalized COVID-19 patients (percent of positive subjects, 30.5) compared to national data in US Black populations (percent of positive subjects, 24.5). The percent B53 positive in non-hospitalized COVID-19 patients was 2.6, significantly less than the percent positive in the hospitalized COVID-19 patients (p = 0.001, Fisher's exact test) and less than the 8 percent positive listed in national data bases for US Caucasian populations. Significantly greater deaths (73 percent) were observed in HLA B53 positive hospitalized COVID-19 patients compared to hospitalized COVID-19 patients who were B53 negative (40 percent). Multi-variate analysis indicated that HLA B53 positive Black hospitalized COVID-19 patients were at a 7.4 fold greater risk of death than Black COVID-19 patients who were B53 negative. Consideration for accelerated vaccination and treatment should be given to HLA B53 positive Black COVID19 patients.


Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease/genetics , HLA Antigens/genetics , African Americans/genetics , Female , Hospitalization , Humans , Male , SARS-CoV-2/pathogenicity , United States
7.
Sci Rep ; 11(1): 9905, 2021 05 10.
Article in English | MEDLINE | ID: covidwho-1223111

ABSTRACT

The COVID-19 pandemic has affected African American populations disproportionately with respect to prevalence, and mortality. Expression profiles represent snapshots of combined genetic, socio-environmental (including socioeconomic and environmental factors), and physiological effects on the molecular phenotype. As such, they have potential to improve biological understanding of differences among populations, and provide therapeutic biomarkers and environmental mitigation strategies. Here, we undertook a large-scale assessment of patterns of gene expression between African Americans and European Americans, mining RNA-Seq data from 25 non-diseased and diseased (tumor) tissue-types. We observed the widespread enrichment of pathways implicated in COVID-19 and integral to inflammation and reactive oxygen stress. Chemokine CCL3L3 expression is up-regulated in African Americans. GSTM1, encoding a glutathione S-transferase that metabolizes reactive oxygen species and xenobiotics, is upregulated. The little-studied F8A2 gene is up to 40-fold more highly expressed in African Americans; F8A2 encodes HAP40 protein, which mediates endosome movement, potentially altering the cellular response to SARS-CoV-2. African American expression signatures, superimposed on single cell-RNA reference data, reveal increased number or activity of esophageal glandular cells and lung ACE2-positive basal keratinocytes. Our findings establish basal prognostic signatures that can be used to refine approaches to minimize risk of severe infection and improve precision treatment of COVID-19 for African Americans. To enable dissection of causes of divergent molecular phenotypes, we advocate routine inclusion of metadata on genomic and socio-environmental factors for human RNA-sequencing studies.


Subject(s)
African Americans/genetics , COVID-19/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Neoplasms/genetics , /genetics , COVID-19/epidemiology , COVID-19/virology , Chemokine CCL3/genetics , Gene Regulatory Networks , Glutathione Transferase/genetics , Humans , Neoplasms/classification , Neoplasms/ethnology , Nuclear Proteins/genetics , Pandemics , Prognosis , RNA-Seq/methods , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Socioeconomic Factors , United States/epidemiology
9.
PLoS One ; 15(12): e0244270, 2020.
Article in English | MEDLINE | ID: covidwho-992713

ABSTRACT

OBJECTIVE: To evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH). METHODS: The MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N = 866 patients hospitalized with Covid-19 from March 11, 2020-May 4, 2020. RESULTS: Overall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR = (48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR = (40.6, 61.6) versus 72y; (58.0, 81.7) (p<0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p = 0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p<0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p<0.001; OR = 1.99, p = 0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p<0.001). CONCLUSIONS: Hospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.


Subject(s)
COVID-19/epidemiology , SARS-CoV-2/pathogenicity , African Americans/genetics , Aged , COVID-19/genetics , COVID-19/virology , Electronic Health Records , Female , Hospital Mortality , Hospitals, General , Humans , Male , Middle Aged , SARS-CoV-2/genetics , /genetics
10.
Ther Adv Cardiovasc Dis ; 14: 1753944720977715, 2020.
Article in English | MEDLINE | ID: covidwho-962356

ABSTRACT

COVID-19 is said to be a pandemic that does not distinguish between skin color or ethnic origin. However, data in many parts of the world, especially in the United States, begin to show that there is a sector of society suffering a more significant impact from this pandemic. The Black population is more vulnerable than the White population to infection and death by COVID-19, with hypertension and diabetes mellitus as probable predisposing factors. Over time, multiple disparities have been observed between the health of Black and White populations, associated mainly with socioeconomic inequalities. However, some mechanisms and pathophysiological susceptibilities begin to be elucidated that are related directly to the higher prevalence of multiple diseases in the Black population, including infection and death by COVID-19. Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system (RAAS) in Black people differ considerably from those of other races. The role of these factors in the development and progression of hypertension and multiple lung diseases, among them SARS-CoV-2 infection, is well established. In this sense, the present review attempts to elucidate the link between vitamin D and RAAS ethnic disparities and susceptibility to infection and death by COVID-19 in Black people, and suggests possible mechanisms for this susceptibility.


Subject(s)
African Americans/genetics , COVID-19/mortality , Health Status Disparities , Renin-Angiotensin System/genetics , Social Determinants of Health/ethnology , Socioeconomic Factors , Vitamin D Deficiency/mortality , Vitamin D/analogs & derivatives , Biomarkers/blood , COVID-19/ethnology , COVID-19/genetics , Genetic Predisposition to Disease , Humans , Race Factors , Risk Assessment , Risk Factors , United States/epidemiology , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/ethnology
11.
J Am Soc Nephrol ; 32(1): 33-40, 2021 01.
Article in English | MEDLINE | ID: covidwho-937294

ABSTRACT

BACKGROUND: Studies have documented AKI with high-grade proteinuria in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some patients, biopsies have revealed collapsing glomerulopathy, a distinct form of glomerular injury that has been associated with other viruses, including HIV. Previous patient reports have described patients of African ancestry who developed nephrotic-range proteinuria and AKI early in the course of disease. METHODS: In this patient series, we identified six patients with coronavirus disease 2019 (COVID-19), AKI, and nephrotic-range proteinuria. COVID-19 was diagnosed by a positive nasopharyngeal swab RT-PCR for SARS-CoV-2 infection. We examined biopsy specimens from one transplanted kidney and five native kidneys. Three of the six patients underwent genetic analysis of APOL1, the gene encoding the APOL1 protein, from DNA extracted from peripheral blood. In addition, we purified genomic DNA from paraffin-embedded tissue and performed APOL1 genotype analysis of one of the native biopsies and the donor kidney graft. RESULTS: All six patients were of recent African ancestry. They developed COVID-19-associated AKI with podocytopathy, collapsing glomerulopathy, or both. Patients exhibited generally mild respiratory symptoms, and no patient required ventilator support. Genetic testing performed in three patients confirmed high-risk APOL1 genotypes. One APOL1 high-risk patient developed collapsing glomerulopathy in the engrafted kidney, which was transplanted from a donor who carried a low-risk APOL1 genotype; this contradicts current models of APOL1-mediated kidney injury, and suggests that intrinsic renal expression of APOL1 may not be the driver of nephrotoxicity and specifically, of podocyte injury. CONCLUSIONS: Glomerular disease presenting as proteinuria with or without AKI is an important presentation of COVID-19 infection and may be associated with a high-risk APOL1 genotype.


Subject(s)
Acute Kidney Injury/etiology , African Americans , Apolipoprotein L1/genetics , COVID-19/complications , Kidney Glomerulus/physiopathology , SARS-CoV-2 , Acute Kidney Injury/ethnology , Acute Kidney Injury/genetics , Acute Kidney Injury/physiopathology , African Americans/genetics , Apolipoprotein L1/physiology , Biopsy , Diabetic Nephropathies/complications , Female , Genetic Predisposition to Disease , Genotype , Hematuria/etiology , Humans , Hypertension/complications , Kidney Glomerulus/pathology , Kidney Transplantation , Male , Middle Aged , Models, Biological , Podocytes/pathology , Podocytes/virology , Proteinuria/etiology , Risk , SARS-CoV-2/pathogenicity , Viral Tropism
14.
Immunogenetics ; 72(6-7): 387-391, 2020 09.
Article in English | MEDLINE | ID: covidwho-690803

ABSTRACT

Covid-19 has caused worldwide devastation. IFIH1 is a pattern recognition receptor that senses coronavirus RNA and triggers interferon production as a first line of viral immune defense. The role of IFIH1 polymorphism, rs1990760 (C>T; aaA946T) in the epidemiology of viral infection is well studied, and the minor allele T resists viral infection. Knock-in mice with mutated IFIH1 protein (946T) for this allele have enhanced interferon production and protection from lethal viral infection. The minor allele frequency (Tmaf) varies widely from Africans (0.06 to 0.35) to Chinese (0.19 to 0.23) to Caucasians (0.56 to 0.69). During the initial days of infection when the social restrictions were not imposed, I show that the infection rate in Italy was lower as expected from its higher Tmaf (0.56) than that in China (Tmaf for southern China, 0.23). The infection rate in the USA and Spain was intermediate between those two countries despite higher Caucasian overall Tmaf (0.69), perhaps due to a more admixed African population in these countries. These analyses suggest that African-Americans and Chinese with low Tmaf of rs1990760 are more vulnerable to SARS-COV2 infection, apart from other genetic factors or socioeconomic conditions in these population. Taken together, an IFN-beta supplement might aid in preventing COVID-19 infection and help in development of herd immunity.


Subject(s)
African Americans/genetics , Coronavirus Infections/genetics , Genetic Predisposition to Disease , Interferon-Induced Helicase, IFIH1/genetics , Pneumonia, Viral/genetics , Betacoronavirus , COVID-19 , China , Gene Frequency , Genotype , Humans , Interferon-beta , Italy , Pandemics , Polymorphism, Single Nucleotide , SARS-CoV-2 , United States
15.
Clin Appl Thromb Hemost ; 26: 1076029620943671, 2020.
Article in English | MEDLINE | ID: covidwho-676150

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.


Subject(s)
African Americans , Betacoronavirus , Coronavirus Infections/ethnology , Pandemics , Pneumonia, Viral/ethnology , Thrombophilia/ethnology , Venous Thromboembolism/ethnology , African Americans/genetics , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/ethnology , Anticoagulants/therapeutic use , Blood Proteins/analysis , Blood Proteins/genetics , COVID-19 , Clinical Trials as Topic , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/complications , Factor VIII/analysis , Female , Fibrin Fibrinogen Degradation Products/analysis , Genetic Association Studies , Genetic Predisposition to Disease , Healthcare Disparities , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/ethnology , Male , Patient Selection , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Polymorphism, Single Nucleotide , Prevalence , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/ethnology , Risk Factors , SARS-CoV-2 , Social Determinants of Health , Socioeconomic Factors , Thrombophilia/blood , Thrombophilia/drug therapy , Thrombophilia/etiology , Venous Thromboembolism/blood , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
16.
Eur J Haematol ; 105(5): 519-523, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-615363

ABSTRACT

Coronavirus Disease 2019 (COVID-19) pandemic is a rapidly evolving public health problem. The severity of COVID-19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID-19 among African Americans, although detailed epidemiological study data is pending. Sickle cell disease (SCD) disproportionately affects Black/African Americans in the United States as well as forebearers from sub-Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America), and some Mediterranean countries. The carrier frequency for SCD is high among African Americans. This article underscores the putative risks that may be associated with COVID-19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine.


Subject(s)
COVID-19/complications , Sickle Cell Trait/complications , African Americans/genetics , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/genetics , COVID-19/epidemiology , COVID-19/mortality , Humans , Pandemics , Precision Medicine , Risk Factors , SARS-CoV-2 , Sickle Cell Trait/epidemiology , Sickle Cell Trait/genetics , United States/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL