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1.
J Clin Endocrinol Metab ; 107(2): e698-e707, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1394502

ABSTRACT

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.


Subject(s)
COVID-19/complications , Obesity/complications , Systemic Inflammatory Response Syndrome/etiology , Adult , Aged , Aged, 80 and over , Aging , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/mortality , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Interleukin-6/blood , Leukocyte Count , Male , Middle Aged , Obesity/mortality , Risk Factors , Systemic Inflammatory Response Syndrome/mortality , Treatment Outcome , United States/epidemiology
2.
Diabetes Res Clin Pract ; 178: 108953, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1322065

ABSTRACT

AIMS: We sought to investigate whether individuals with diabetes have a higher likelihood of testing positive for SARS-CoV-2, as a proxy for infection risk, than individuals without diabetes. METHODS: We conducted a cross-sectional study of publicly available data among a Mexican population, totaling 2,314,022 adults ≥ 18 years who underwent SARS-CoV-2 testing between March 1 and December 20, 2020. We used 1:1 nearest neighborhood propensity score matching by diabetes status to account for confounding among those with and without diabetes. RESULTS: In the overall study population, 1,057,779 (45.7%) individuals tested positive for SARS-CoV-2 and 270,486 (11.7%) self-reported diabetes. After propensity score matching, patient characteristics were well-balanced, with 150,487 patients in the diabetes group (mean [SD] age 55.9 [12.7] years; 51.3% women) and 150,487 patients in the no diabetes group (55.5 [13.3] years; 50.3% women). The strictest matching algorithm (1:1 nearest neighbor) showed that compared to individuals without diabetes, having diabetes was associated with 9.0% higher odds of having a positive SARS-CoV-2 test (OR 1.09 [95% CI: 1.08-1.10]). CONCLUSIONS: Presence of diabetes was associated with higher odds of testing positive for SARS-CoV-2, which could have important implications for risk mitigation efforts for people with diabetes at risk of SARS-CoV-2 infection.


Subject(s)
COVID-19 , Diabetes Mellitus , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19 Testing , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Female , Humans , Male , Mexico/epidemiology , Middle Aged , Propensity Score , Risk Factors , SARS-CoV-2 , Young Adult
3.
Open Forum Infect Dis ; 8(7): ofab275, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1309622

ABSTRACT

BACKGROUND: Obesity has been linked to severe clinical outcomes among people who are hospitalized with coronavirus disease 2019 (COVID-19). We tested the hypothesis that visceral adipose tissue (VAT) is associated with severe outcomes in patients hospitalized with COVID-19, independent of body mass index (BMI). METHODS: We analyzed data from the Massachusetts General Hospital COVID-19 Data Registry, which included patients admitted with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection from March 11 to May 4, 2020. We used a validated, fully automated artificial intelligence (AI) algorithm to quantify VAT from computed tomography (CT) scans during or before the hospital admission. VAT quantification took an average of 2 ± 0.5 seconds per patient. We dichotomized VAT as high and low at a threshold of ≥100 cm2 and used Kaplan-Meier curves and Cox proportional hazards regression to assess the relationship between VAT and death or intubation over 28 days, adjusting for age, sex, race, BMI, and diabetes status. RESULTS: A total of 378 participants had CT imaging. Kaplan-Meier curves showed that participants with high VAT had a greater risk of the outcome compared with those with low VAT (P < .005), especially in those with BMI <30 kg/m2 (P < .005). In multivariable models, the adjusted hazard ratio (aHR) for high vs low VAT was unchanged (aHR, 1.97; 95% CI, 1.24-3.09), whereas BMI was no longer significant (aHR for obese vs normal BMI, 1.14; 95% CI, 0.71-1.82). CONCLUSIONS: High VAT is associated with a greater risk of severe disease or death in COVID-19 and can offer more precise information to risk-stratify individuals beyond BMI. AI offers a promising approach to routinely ascertain VAT and improve clinical risk prediction in COVID-19.

4.
PLoS Med ; 18(3): e1003553, 2021 03.
Article in English | MEDLINE | ID: covidwho-1117467

ABSTRACT

BACKGROUND: Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses. METHODS AND FINDINGS: We selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10-8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank: odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10-5; UK Biobank: odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10-5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null. CONCLUSIONS: In this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.


Subject(s)
Body Mass Index , COVID-19 , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Disease Susceptibility , Obesity , Renal Insufficiency, Chronic , Stroke , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/genetics , Cardiometabolic Risk Factors , Causality , Coronary Artery Disease/epidemiology , Coronary Artery Disease/genetics , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Genetic Variation , Genome-Wide Association Study/statistics & numerical data , Humans , Mendelian Randomization Analysis , Meta-Analysis as Topic , Obesity/diagnosis , Obesity/epidemiology , Obesity/metabolism , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/genetics , SARS-CoV-2 , Severity of Illness Index , Stroke/epidemiology , Stroke/genetics
5.
J Infect Dis ; 223(1): 38-46, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1066343

ABSTRACT

BACKGROUND: We sought to develop an automatable score to predict hospitalization, critical illness, or death for patients at risk for coronavirus disease 2019 (COVID-19) presenting for urgent care. METHODS: We developed the COVID-19 Acuity Score (CoVA) based on a single-center study of adult outpatients seen in respiratory illness clinics or the emergency department. Data were extracted from the Partners Enterprise Data Warehouse, and split into development (n = 9381, 7 March-2 May) and prospective (n = 2205, 3-14 May) cohorts. Outcomes were hospitalization, critical illness (intensive care unit or ventilation), or death within 7 days. Calibration was assessed using the expected-to-observed event ratio (E/O). Discrimination was assessed by area under the receiver operating curve (AUC). RESULTS: In the prospective cohort, 26.1%, 6.3%, and 0.5% of patients experienced hospitalization, critical illness, or death, respectively. CoVA showed excellent performance in prospective validation for hospitalization (expected-to-observed ratio [E/O]: 1.01; AUC: 0.76), for critical illness (E/O: 1.03; AUC: 0.79), and for death (E/O: 1.63; AUC: 0.93). Among 30 predictors, the top 5 were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. CONCLUSIONS: CoVA is a prospectively validated automatable score for the outpatient setting to predict adverse events related to COVID-19 infection.


Subject(s)
COVID-19/diagnosis , Severity of Illness Index , Adult , Aged , Critical Illness , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Models, Theoretical , Outpatients , Predictive Value of Tests , Prognosis , Prospective Studies , ROC Curve , Sensitivity and Specificity
7.
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
8.
Diabetes Care ; 44(2): 373-380, 2021 02.
Article in English | MEDLINE | ID: covidwho-934424

ABSTRACT

OBJECTIVE: Diabetes is an important risk factor for severe coronavirus disease 2019 (COVID-19), but little is known about the marginal effect of additional risk factors for severe COVID-19 among individuals with diabetes. We tested the hypothesis that sociodemographic, access to health care, and presentation to care characteristics among individuals with diabetes in Mexico confer an additional risk of hospitalization with COVID-19. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study using public data from the General Directorate of Epidemiology of the Mexican Ministry of Health. We included individuals with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 between 1 March and 31 July 2020. The primary outcome was the predicted probability of hospitalization, inclusive of 8.5% of patients who required intensive care unit admission. RESULTS: Among 373,963 adults with COVID-19, 16.1% (95% CI 16.0-16.3) self-reported diabetes. The predicted probability of hospitalization was 38.4% (37.6-39.2) for patients with diabetes only and 42.9% (42.2-43.7) for patients with diabetes and one or more comorbidities (obesity, hypertension, cardiovascular disease, and chronic kidney disease). High municipality-level of social deprivation and low state-level health care resources were associated with a 9.5% (6.3-12.7) and 17.5% (14.5-20.4) increased probability of hospitalization among patients with diabetes, respectively. In age-, sex-, and comorbidity-adjusted models, living in a context of high social vulnerability and low health care resources was associated with the highest predicted probability of hospitalization. CONCLUSIONS: Social vulnerability contributes considerably to the probability of hospitalization among individuals with COVID-19 and diabetes with associated comorbidities. These findings can inform mitigation strategies for populations at the highest risk of severe COVID-19.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Health Services Accessibility/statistics & numerical data , Hypertension/epidemiology , Obesity/epidemiology , Adult , Aged , Comorbidity , Cross-Sectional Studies , Female , Humans , Intensive Care Units , Male , Mexico/epidemiology , Middle Aged , Risk Factors
9.
Diabetes Care ; 43(12): 2938-2944, 2020 12.
Article in English | MEDLINE | ID: covidwho-732933

ABSTRACT

OBJECTIVE: Diabetes and obesity are highly prevalent among hospitalized patients with coronavirus disease 2019 (COVID-19), but little is known about their contributions to early COVID-19 outcomes. We tested the hypothesis that diabetes is a risk factor for poor early outcomes, after adjustment for obesity, among a cohort of patients hospitalized with COVID-19. RESEARCH DESIGN AND METHODS: We used data from the Massachusetts General Hospital (MGH) COVID-19 Data Registry of patients hospitalized with COVID-19 between 11 March 2020 and 30 April 2020. Primary outcomes were admission to the intensive care unit (ICU), need for mechanical ventilation, and death within 14 days of presentation to care. Logistic regression models were adjusted for demographic characteristics, obesity, and relevant comorbidities. RESULTS: Among 450 patients, 178 (39.6%) had diabetes-mostly type 2 diabetes. Among patients with diabetes versus patients without diabetes, a higher proportion was admitted to the ICU (42.1% vs. 29.8%, respectively, P = 0.007), required mechanical ventilation (37.1% vs. 23.2%, P = 0.001), and died (15.9% vs. 7.9%, P = 0.009). In multivariable logistic regression models, diabetes was associated with greater odds of ICU admission (odds ratio 1.59 [95% CI 1.01-2.52]), mechanical ventilation (1.97 [1.21-3.20]), and death (2.02 [1.01-4.03]) at 14 days. Obesity was associated with greater odds of ICU admission (2.16 [1.20-3.88]) and mechanical ventilation (2.13 [1.14-4.00]) but not with death. CONCLUSIONS: Among hospitalized patients with COVID-19, diabetes was associated with poor early outcomes, after adjustment for obesity. These findings can help inform patient-centered care decision making for people with diabetes at risk for COVID-19.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/mortality , Intensive Care Units , Obesity/mortality , Comorbidity , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Respiration, Artificial/mortality , Risk Factors , SARS-CoV-2
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