Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 25:16:1506065.
doi: 10.3389/fendo.2025.1506065. eCollection 2025.

Pre-existing adipose tissue signaling profile related to obesity determines disease outcome of COVID-19: addressing obesity should be a priority for future pandemic preparedness

Arifa Parker  1 , Kelly Petersen-Ross  2 , Tongai Maponga  3 , Samina Parkar  4 , Nadiya Ahmed  5 , Candice I Snyders  6 , Martin Kidd  7 , Jantjie J Taljaard  8 , Graeme Meintjes  9   10 , Coenraad F N Koegelenberg  11 , Léanie Kleynhans  6   12 , Carine Smith  3
Affiliations

Pre-existing adipose tissue signaling profile related to obesity determines disease outcome of COVID-19: addressing obesity should be a priority for future pandemic preparedness

Arifa Parker et al. Front Endocrinol (Lausanne). .

Abstract

Objectives: Obesity is associated with COVID-19 severity and mortality. We investigated relationships between adipokines, cytokines and redox parameters with obesity, human immunodeficiency virus (HIV), severity and outcome.

Methods: In the exploratory study, adipose tissue (AT) was sampled in patients with COVID-19 on admission. Concentrations of leptin, adiponectin, resistin, interleukin 1 beta (IL-1b), IL-2, IL-6, IL-10, IL-17, tumor necrosis factor alpha (TNF-a), monocyte chemoattractant protein 1 (MCP-1), Trolox equivalent antioxidant capacity (TEAC), oxidative stress (H202) and malonaldehyde (MDA) were determined.

Results: Thirty-eight biopsies of subcutaneous adipose tissue were obtained (prevalence of HIV was 39% and of obesity 61%). Higher IL-6 serum concentrations (p=0.03) were associated with more severe COVID-19, and higher serum IL-10 concentrations, (p=0.03) with mortality. People with obesity had higher leptin concentrations (p=0.03, and p<0.01), lower adiponectin/leptin (p=0.03 and p<0.01), and higher leptin/resistin ratios (p=0.09 and p<0.01) in both AT and serum respectively. Higher leptin/resistin (p=0.04) and lower adiponectin/resistin (p=0.05) ratios in AT, but not serum, were predictive of mortality. HIV was not associated with any differences. Relationships between resistin and redox indicators, TEAC and MDA, suggest a dysregulation of metabolic vs immune-relevant effect of resistin, which differentially predicted severity and mortality. SARS-CoV-2 RNA was detected in the subcutaneous AT in 3/8 patients who demised, but only in 1/30 who survived.

Conclusion: Given the significant link demonstrated between leptin dysregulation in obesity and mortal severity of COVID-19, addressing obesity should be a priority therapeutic target in terms of future pandemic preparedness. Mechanistic studies are recommended to further elucidate the importance of metabolic vs immune modulation by resistin in COVID-19, to identify future therapeutic targets.

Keywords: COVID-19; HIV; adipokine; adiponectin; adipose tissue; leptin; obesity; resistin.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Adipose tissue homogenate levels of H2O2, MDA and Trolox equivalent antioxidant capacity stratified by (a–c) obesity, (d–e) outcome, (g–i) COVID-19 severity.
Figure 2
Figure 2
(a) Adipose tissue homogenate levels of Trolox equivalent antioxidant capacity (TEAC) in correlation to the ratio of leptin/resistin for patients classified as non-obese (a) and obese (b), as well as the ratio of adiponectin/resistin in non-obese (c) and obese (d) patients.
Figure 3
Figure 3
Adipose tissue homogenate levels of resistin in comparison to Trolox equivalent antioxidant capacity for patients classified as early severe disease (a) and advanced severe disease (b), resistin in comparison to malondialdehyde (MDA) for patients without obesity (c) and patients with obesity (d) and resistin in comparison to malondialdehyde (MDA) for patients classified as surviving (e) and non-surviving (f).
See this image and copyright information in PMC

References

    1. Ryan PMD, Caplice NM. Is adipose tissue a reservoir for viral spread, immune activation, and cytokine amplification in coronavirus disease 2019? In: Obesity, vol. 28. New Jersey, United States: Blackwell Publishing Inc; (2020). p. 1191–4. doi: 10.1002/oby.22843 - DOI - PMC - PubMed
    1. Cypess AM. Reassessing human adipose tissue. New Engl J Med. (2022) 386:768–79. doi: 10.1056/NEJMra2032804 - DOI - PubMed
    1. Gao M, Piernas C, Astbury NM, Hippisley-Cox J, O’Rahilly S, Aveyard P, et al. . Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study. Lancet Diabetes Endocrinol. (2021) 9:350–9. doi: 10.1016/S2213-8587(21)00089-9 - DOI - PMC - PubMed
    1. Parker A, Boloko L, Moolla MS, Ebrahim N, Ayele BT, Broadhurst AGB, et al. . Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study. BMC Infect Dis. (2022) 22. doi: 10.1186/s12879-022-07519-8 - DOI - PMC - PubMed
    1. Maurya R, Sebastian P, Namdeo M, Devender M, Gertler A. COVID-19 severity in obesity: leptin and inflammatory cytokine interplay in the link between high morbidity and mortality. Front Immunol. (2021) 12:649359. doi: 10.3389/fimmu.2021.649359 - DOI - PMC - PubMed

MeSH terms