Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response

Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. This hospital-based, observational study included 3828 SARS-...

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Published in:The journal of clinical endocrinology and metabolism Vol. 107; no. 2; p. e698
Main Authors: Foulkes, Andrea S, Selvaggi, Caitlin, Shinnick, Daniel, Lumish, Heidi, Kim, Eunyoung, Cao, Tingyi, Thaweethai, Tanayott, Qian, Jing, Lu, Frances, Yan, Joyce, Cheng, David, He, Wei, Clerkin, Kevin J, Madhavan, Mahesh V, Meigs, James B, Triant, Virginia A, Lubitz, Steven A, Gupta, Aakriti, Bassett, Ingrid V, Reilly, Muredach P
Format: Journal Article
Language:English
Published: United States 01.02.2022
Subjects:
Adult
Aged
Aged, 80 and over
Aging
Blood Sedimentation
C-Reactive Protein - analysis
COVID-19 - complications
COVID-19 - mortality
Female
Ferritins - blood
Fibrin Fibrinogen Degradation Products - analysis
Humans
Interleukin-6 - blood
Leukocyte Count
Male
Middle Aged
Obesity - complications
Obesity - mortality
Risk Factors
Systemic Inflammatory Response Syndrome - etiology
Systemic Inflammatory Response Syndrome - mortality
Treatment Outcome
United States - epidemiology
United States
COVID-19
severe disease
SARS-CoV-2
inflammation
biomarkers
obesity
ISSN:1945-7197, 1945-7197
Online Access:Get more information
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Summary:Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. 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. 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). 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.
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ISSN:1945-7197
1945-7197
DOI:10.1210/clinem/dgab629