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2.
Hum Mol Genet ; 31(14): 2452-2461, 2022 Jul 21.
Article in English | MEDLINE | ID: covidwho-1713662

ABSTRACT

BACKGROUND: Genome-wide association studies have identified six genetic variants associated with severe COVID-19, yet the mechanisms through which they may affect disease remains unclear. We investigated proteomic signatures related to COVID-19 risk variants rs657152 (ABO), rs10735079 (OAS1/OAS2/OAS3), rs2109069 (DPP9), rs74956615 (TYK2), rs2236757 (IFNAR2) and rs11385942 (SLC6A20/LZTFL1/CCR9/FYCO1/CXCR6/XCR1) as well as their corresponding downstream pathways that may promote severe COVID-19 in risk allele carriers and their potential relevancies to other infection outcomes. METHODS: A DNA aptamer-based array measured 4870 plasma proteins among 11 471 participants. Linear regression estimated associations between the COVID-19 risk variants and proteins with correction for multiple comparisons, and canonical pathway analysis was conducted. Cox regression assessed associations between proteins identified in the main analysis and risk of incident hospitalized respiratory infections (2570 events) over a 20.7-year follow-up. RESULTS: The ABO variant rs657152 was associated with 84 proteins in 7241 white participants with 24 replicated in 1671 Black participants. The TYK2 variant rs74956615 was associated with ICAM-1 and -5 in white participants with ICAM-5 replicated in Black participants. Of the 84 proteins identified in the main analysis, seven were significantly associated with incident hospitalized respiratory infections including Ephrin type-A receptor 4 (hazard ratio (HR): 0.87; P = 2.3 × 10-11) and von Willebrand factor type A (HR: 1.17; P = 1.6x10-13). CONCLUSIONS: Novel proteomics signatures and pathways for COVID-19-related risk variants TYK2 and ABO were identified. A subset of these proteins predicted greater risk of incident hospitalized pneumonia and respiratory infections. Further studies to examine these proteins in COVID-19 patients are warranted.


Subject(s)
COVID-19 , Genetic Predisposition to Disease , COVID-19/genetics , Genome-Wide Association Study , Humans , Proteomics , Risk Factors
3.
BMJ Open ; 11(12): e053542, 2021 12 02.
Article in English | MEDLINE | ID: covidwho-1550961

ABSTRACT

OBJECTIVES: We aimed to ascertain the prevalence of perceived loneliness among older adults following the onset of the COVID-19 pandemic and to examine factors contributing to the perception of loneliness. DESIGN: Cross-sectional and longitudinal data from the Atherosclerosis Risk in Communities (ARIC) Study cohort. SETTING: The ARIC Study cohort, a prospective cohort that recruited (1987-1989) participants from four distinct communities in the USA. PARTICIPANTS: 2984 ARIC cohort members. PRIMARY AND SECONDARY OUTCOMES: Perceived loneliness assessed using the University of California at Los Angeles (UCLA) UCLA three-item Loneliness Scale telephone interviews conducted May-October 2020 and prior to March 2020. RESULTS: Of the total 5037 participants alive in 2020, 2984 (56.2%) responded to the UCLA three-item questionnaire (mean age 82.6 (SD 4.6) years, 586 (19.6%) black participants, 1081 (36.2%) men), of which 66 (2.2%) reported having had a COVID-19 infection during the observation period. The proportion of participants reporting feeling lonely was 56.3% (n=1680). Among participants with repeat measures of loneliness (n=516), 35.2% (n=182) reported feeling more lonely following pandemic onset. Self-rated health and emotional resilience were strongly associated with self-perceived loneliness. The burden of COVID-19 infections, concern about the pandemic and decreased self-reported physical activity were greater among black as compared with white participants and among those with an educational attainment of less than high school as compared with high school or more. CONCLUSION: Findings from this study document the increase in perceived loneliness among older adults during the COVID-19 pandemic in the USA.


Subject(s)
Atherosclerosis , COVID-19 , Aged , Aged, 80 and over , Atherosclerosis/epidemiology , Cross-Sectional Studies , Humans , Loneliness , Longitudinal Studies , Male , Pandemics , Prospective Studies , SARS-CoV-2
4.
EClinicalMedicine ; 41: 101139, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1433165

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

5.
Thorax ; 76(7): 704-713, 2021 07.
Article in English | MEDLINE | ID: covidwho-1322844

ABSTRACT

BACKGROUND: Poor sleep may contribute to chronic kidney disease (CKD) through several pathways, including hypoxia-induced systemic and intraglomerular pressure, inflammation, oxidative stress and endothelial dysfunction. However, few studies have investigated the association between multiple objectively measured sleep dimensions and CKD. METHODS: We investigated the cross-sectional association between sleep dimensions and CKD among 1895 Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study participants who completed in-home polysomnography, wrist actigraphy and a sleep questionnaire. Using Poisson regression models with robust variance, we estimated separate prevalence ratios (PR) and 95% CIs for moderate-to-severe CKD (glomerular filtration rate <60 mL/min/1.73 m2 or albuminuria >30 mg/g) among participants according to multiple sleep dimensions, including very short (≤5 hours) sleep, Apnoea-Hypopnoea Index and sleep apnoea-specific hypoxic burden (SASHB) (total area under the respiratory event-related desaturation curve divided by total sleep duration, %min/hour)). Regression models were adjusted for sociodemographic characteristics, health behaviours and clinical characteristics. RESULTS: Of the 1895 participants, mean age was 68.2±9.1 years, 54% were women, 37% were white, 28% black, 24% Hispanic/Latino and 11% Asian. Several sleep metrics were associated with higher adjusted PR of moderate-to-severe CKD: very short versus recommended sleep duration (PR=1.40, 95% CI 1.06 to 1.83); SASHB (Box-Cox transformed SASHB: PR=1.06, 95% CI 1.02 to 1.12); and for participants in the highest quintile of SASHB plus sleep apnoea: PR=1.28, 95% CI 1.01 to 1.63. CONCLUSIONS: Sleep apnoea associated hypoxia and very short sleep, likely representing independent biological mechanisms, were associated with a higher moderate-to-severe CKD prevalence, which highlights the potential role for novel interventions.


Subject(s)
Atherosclerosis/complications , Hypoxia/etiology , Renal Insufficiency, Chronic/complications , Sleep Apnea Syndromes/complications , Sleep/physiology , Actigraphy , Aged , Aged, 80 and over , Atherosclerosis/ethnology , Cross-Sectional Studies , Female , Humans , Hypoxia/physiopathology , Male , Middle Aged , Polysomnography , Prevalence , Renal Insufficiency, Chronic/ethnology , Risk Factors , Self Report , Sleep Apnea Syndromes/ethnology , Sleep Apnea Syndromes/physiopathology , United States/epidemiology
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