Biomarker Mediation of Obesity and Severe COVID-19

Andrea S Foulkes, Caitlin Selvaggi, Daniel Shinnick, Heidi Lumish, Eunyoung Kim, Tingyi Cao, Tanayott Thaweethai, Jing Qian, Frances Lu, Joyce Yan, David Cheng, Wei He, Kevin J Clerkin, Mahesh V Madhavan, James B Meigs, Virginia A Triant, Steven A Lubitz, Aakriti Gupta, Ingrid V Bassett, Muredach P Reilly
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 2, February 2022, Pages e698–e707
https://doi.org/10.1210/clinem/dgab629

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.

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