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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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism Jg. 107; H. 2; S. e698 |
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01.02.2022
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| Abstract | 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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| AbstractList | Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood.BACKGROUNDObesity 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.OBJECTIVETo 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.METHODSThis 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).RESULTSIn 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.CONCLUSIONFindings 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. 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. |
| Author | Triant, Virginia A Reilly, Muredach P Lumish, Heidi Thaweethai, Tanayott Clerkin, Kevin J Meigs, James B Bassett, Ingrid V Madhavan, Mahesh V Selvaggi, Caitlin Cao, Tingyi Yan, Joyce Kim, Eunyoung Foulkes, Andrea S Shinnick, Daniel Qian, Jing Lubitz, Steven A Gupta, Aakriti He, Wei Cheng, David Lu, Frances |
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| Keywords | COVID-19 severe disease SARS-CoV-2 inflammation biomarkers obesity |
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| Snippet | Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood.
To evaluate the... Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood.BACKGROUNDObesity... |
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| SubjectTerms | 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 |
| Title | Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response |
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