COVID-19 and obesity: 2025 perspective on epidemiology, pathogenesis, and public health implications

Introduction

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1), has triggered one of the most significant pandemics in human history (2). Accurately assessing the cumulative number of deaths attributed to COVID-19 is challenging due to widespread underreporting and inconsistencies in death classification across countries (e.g., deaths “from” or “with” COVID-19) (3). Although the World Health Organization (WHO) estimates that over 7 million deaths could be linked to SARS-CoV-2 infection by the end of 2024 (4), this figure likely underrepresents the true toll, with some estimates suggesting the actual number of deaths may be 2–4 times higher (5). Evidence indicates that the majority of these deaths have occurred among the most vulnerable populations, particularly the elderly and individuals with multiple comorbidities (1,6).

Concurrently, obesity represents a parallel yet less visible pandemic, impacting numerous regions globally and contributing to increased morbidity and mortality (7). Excess body weight is strongly associated with a heightened risk of cardiovascular disease (CVD), type 2 diabetes, cancer, and various chronic conditions such as osteoarthritis, liver and kidney diseases, sleep apnea, and depression (7). Emerging evidence underscores that individuals who are overweight [e.g., traditionally with body mass index (BMI) between 25 and 29.9 kg/m²] or obese (e.g., typically with BMI ≥30 kg/m²) face an elevated risk of SARS-CoV-2 infection and are more likely to experience severe outcomes of COVID-19, including higher rates of hospitalization, admission to intensive care units (ICUs), and mortality, compared to individuals with normal weight.

Epidemiological evidence

A comprehensive meta-analysis published in late 2020, during the early phase of the pandemic, analyzed data from 50 studies encompassing 18,260,378 COVID-19 patients (8) and concluded that individuals with BMI ≥30 kg/m² were 1.39 times more likely to be infected by SARS-CoV-2 compared to those with a healthy weight. Furthermore, the risk of hospitalization increased in a dose-response manner, as the odds ratio (OR) was 2.09 for overweight individuals, 2.45 for those with obesity, and 2.63 for those with severe obesity (BMI ≥35 kg/m²). Obese patients were also 3.74 times more likely to develop severe COVID-19 than individuals with BMI <30 kg/m². The likelihood of requiring ICU admission was 1.30 times higher for individuals with obesity, rising to 1.86 times for severe obesity. The need for mechanical ventilation was significantly elevated in patients with BMI ≥25 kg/m², with ORs of 1.40 for overweight, 1.59 for obesity, and 5.22 for severe obesity. Mortality risk also showed a dose-response pattern, with an OR of 1.65 for patients with BMI ≥30 kg/m², further increasing to 1.91 for those with BMI between 35 and 39.9 kg/m² (8). Another meta-analysis, published in 2020 by Sharma et al. and including 13 studies with a total of 7,196 patients, examined COVID-19 outcomes based on BMI (9). The analysis found that obesity was associated with a 39% increased risk (OR: 1.39) of severe disease, defined as the need for intensive care, invasive mechanical ventilation, hospital admission, or death.

A more recent meta-analysis published in 2024, including 15 prospective studies with 1,813,472 participants aged ranging from 15 to over 80 years (10), found that obesity increased the risk of death from COVID-19 by over 50% [OR 1.52; 95% confidence interval (CI): 1.26–1.84]. Another meta-analysis published by Haber et al., encompassing 199 studies with a mean age range of 41.8–78.2 years (11), showed a 32% higher risk of death for patients with obesity compared to those with normal body weight (OR 1.32; 95% CI: 1.18–1.48).

Interestingly, a prospective study of 95 patients admitted to the ICU with severe COVID-19 illness revealed that obese individuals had longer ICU stays (18 vs. 14 days) and lower 28-day survival rates than patients with normal weight (defined as BMI <27 kg/m²) (12). Specifically, the hazard ratio (HR) for mortality was 5.30 (95% CI: 1.26–22.34) for obese patients, while overweight individuals (defined as having a BMI between 27 and 29.9 kg/m²) demonstrated a moderately elevated risk of death compared to those with normal weight (HR 1.13; 95% CI: 1.05–1.21).

Collectively, these epidemiological findings confirm the existence of a clear dose-response relationship between BMI and adverse COVID-19 outcomes, including infection risk, hospitalization, need for mechanical ventilation, ICU admission, and mortality (13). Intriguingly, abdominal obesity appears to exacerbate further the risk of adverse outcomes in overweight or obese patients with SARS-CoV-2 infection (14).

Unraveling the biological link between COVID-19 and obesity

The mechanisms underlying the increased risk of severe disease among individuals with obesity involve a variety of biological pathways, encompassing immune dysfunction (including lowered response to COVID-19 vaccination), chronic inflammation, and the presence of several comorbidities (Figure 1).

Figure 1 The complex interplay between obesity and COVID-19 and its implications for health outcomes. COVID-19, coronavirus disease 2019.

Immune dysfunction

The innate immune system, which plays a crucial role in defending against infections, is often impaired in overweight and obese individuals, leading to a less effective response to viral pathogens. In line with this, a study by Tong et al. investigated 82 patients who had recovered from SARS-CoV-2 infection, including 45 with BMI ≥25 kg/m², and collected blood samples at 3- and 13-month post-recovery (15). Patients with higher BMI demonstrated reduced antibody response, as reflected by lower antibody levels at 3 months post-infection, as well as decreased antibody avidity and lower percentage of spike-positive B cells at 13 months post-infection. Another study by Madruga et al. studied 50 hospitalized COVID-19 patients who required low-flow oxygen supplementation (16), reporting that the proportion of mature natural killer (NK) cells was significantly lower in overweight and obese patients compared to those with normal weight.

Similar findings have emerged from studies investigating immune responses following vaccination. For example, van der Klaauw et al. conducted a prospective longitudinal study involving 28 individuals with severe obesity (BMI >40 kg/m²) and 41 individuals with normal BMI (18.5–24.9 kg/m²) who received two doses of COVID-19 vaccine (17). Among individuals with severe obesity, 55% had unmeasurable levels of SARS-CoV-2 neutralizing antibodies 6 months after the second dose, compared to only 12% of those with normal BMI (P<0.001). Furthermore, neutralizing capacity was significantly lower in patients with severe obesity compared to those with normal BMI.

These findings are supported by research from Jang et al., which demonstrated that SARS-CoV-2 receptors are markedly over-expressed in adipose tissue, facilitating viral entry, replication, and release of inflammatory mediators (18). This obesity-associated inflammatory response impairs cellular and humoral immunity, contributing to abnormal lymphocyte differentiation and premature exhaustion. Consequently, the accelerated decline in SARS-CoV-2 antibody levels together with NK and lymphocyte exhaustion may hinder virus clearance, leading to persistent infection and more severe clinical outcomes in COVID-19 patients.

The NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome is a critical component of the innate immune system and a key regulator of inflammation. Growing evidence indicates that NLRP3 inflammasome activation is significantly elevated in patients with COVID-19, particularly in those with severe disease. This activation promotes the release of interleukin (IL)-1β, contributing to excessive inflammation and the progression toward a cytokine storm (19). Consequently, targeting the NLRP3 inflammasome with specific inhibitors such as colchicine has shown promising potential in the treatment of COVID-19, particularly in overweight and obese patients, who are at higher risk for severe disease (20-22).

Chronic, low-grade inflammation

The presence of chronic, low-grade inflammation is prevalent in individuals with overweight and, particularly, obese (23). Given that the pathogenesis and, notably, the adverse clinical progression of COVID-19 are closely linked to sustained inflammatory reactions, such as the development of a cytokine storm (24), the persistent pro-inflammatory state associated with obesity may exacerbate the acute inflammatory response triggered by SARS-CoV-2, thereby accelerating the onset of severe complications, including cytokine release syndrome, acute respiratory distress syndrome (ARDS), and multiple organ failure (1). In a study by Saccon et al., postmortem analysis of 47 subcutaneous adipose tissue samples from individuals who died from COVID-19 revealed sustained expression of pro-inflammatory genes such as IFNA, IL-6, and CCL2 (25). In a subsequent investigation, Fessler et al. measured pro-inflammatory cytokine levels in 60 patients with SARS-CoV-2 infection and found that higher BMI was significantly associated with elevated levels of IL-6, ferritin, high-sensitivity C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), IL-12, and IL-13 (26). A comprehensive study by Reiterer et al. involving 3,854 hospitalized COVID-19 patients demonstrated that efficient infection of human adipose tissue by SARS-CoV-2 was not only linked to a robust systemic inflammatory response, but also led to reduced circulating adiponectin, insulin resistance, and hyperglycemia, thereby predisposing patients to more severe disease outcomes, including ARDS and increased mortality (27). Finally, the elevated leptin concentrations frequently observed in obese individuals may amplify the inflammatory response following SARS-CoV-2 infection (28).

Obesity, comorbidities and COVID-19

The relationship between comorbidities and the risk of adverse clinical outcomes in patients with SARS-CoV-2 infection has been clearly established, with a significantly higher risk of severe progression and mortality observed in those with multiple comorbidities, far exceeding the risks associated with other common conditions, such as cancer and CVD (29). Overweight and obese individuals are notably more susceptible to developing a range of comorbidities, with an elevated BMI being widely recognized as a major risk factor for numerous chronic diseases. Excess body fat, particularly visceral adiposity, contributes to insulin resistance, chronic inflammation, and metabolic dysfunction, all of which foster the development or exacerbation of additional pathologies, including CVD, type 2 diabetes, malignancies (especially breast, colon, endometrial, liver, and kidney cancers), endocrine disorders (such as polycystic ovary syndrome and thyroid disorders), mental health conditions (e.g., anxiety and depression), obstructive sleep apnea, and liver and kidney dysfunction (30). Consequently, the high burden of comorbidities commonly observed in overweight and obese patients creates a particularly vulnerable clinical profile, significantly elevating their risk of poor outcomes and death in the context of SARS-CoV-2 infection.

Public health implications

As the COVID-19 and obesity pandemics continue to evolve, the complex interplay between increased BMI and SARS-CoV-2 infection carries significant public health implications. Obesity not only increases the risk of severe COVID-19 outcomes, such as hospitalization, ICU admission, and mortality but also exacerbates pre-existing health disparities, especially in vulnerable populations. The elevated risk stems from excess adipose tissue, particularly visceral fat, contributing to immune dysfunction, systemic inflammation, and enhanced burden of comorbidities. Addressing obesity in the context of the COVID-19 pandemic through targeted public health interventions seems hence crucial at this point.

Obesity must be prioritized as a worldwide public health concern. Thus, strategies focused on reducing the burden of obesity and promoting healthier lifestyles are essential to safeguard the health of fragile populations at higher risk of unfavorable COVID-19 clinical progression. Addressing these challenges with comprehensive health policies and targeted interventions is crucial for improving health outcomes during and even after the pandemic, as obesity remains a critical concern in the fight against COVID-19. In particular, nutritional strategies that support immune function and overall health can play a critical role in contrasting the deleterious effects of COVID-19 effects on overweight and obese individuals. Reliable evidence suggests that even a modest weight loss—between 5% and 10% of body weight—may improve the metabolic profile and lower inflammation in patients with SARS-CoV-2 infection (31). This can be achieved through caloric restriction, balanced nutrition, and regular physical activity, promoting weight loss and improving immune responses, thereby reducing the likelihood of severe infections and complications from COVID-19.

Public health campaigns must be intensified to educate individuals about the risks of overweight and obesity in relation to COVID-19. Clear, accessible messaging about the importance of maintaining a healthy weight and making lifestyle changes, such as improving diet and increasing physical activity, should be prioritized to reach diverse populations. Moreover, public health messages must emphasize the crucial connection between obesity and other comorbidities, such as CVD, type 2 diabetes, and respiratory disorders, which further exacerbate the clinical progression of COVID-19.

Policy changes that support the reduction of obesity and related health risks are indispensable. For example, taxation on sugary beverages, subsidies for healthy foods, and investment in active transport infrastructure, such as cycling lanes and pedestrian-friendly spaces, can help create an environment that encourages healthier choices. Furthermore, workplace wellness programs, school-based interventions, and community-level initiatives can promote physical activity, healthier eating, and weight management (i.e., walking clubs or cooking classes), as shown in a recent study which found that COVID-19 patients with higher cardiorespiratory fitness had lower risk of death, hospitalization and intubation, independent of age, BMI and comorbidities (32). It is equally important to implement policies that ensure equitable access to obesity management services, especially in underserved communities, to reduce disparities in health outcomes.

Conclusions

Preventing obesity by integrating weight management into the broader public health response to COVID-19 is not just a strategy for improving short-term pandemic outcomes but also an investment in the long-term health of populations worldwide. By tackling obesity through preventive measures, early interventions, and systemic changes, the clinical, social, and economic burden of the interplay between obesity and COVID-19 can be mitigated, fostering healthier and more resilient populations.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://jlpm.amegroups.com/article/view/10.21037/jlpm-24-57/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jlpm.amegroups.com/article/view/10.21037/jlpm-24-57/coif). G.L. serves as an Editor-in-Chief of Journal of Laboratory and Precision Medicine. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Lippi G, Sanchis-Gomar F, Henry BM. Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Ann Transl Med 2020;8:497. [Crossref] [PubMed]
2. Sampath S, Khedr A, Qamar S, et al. Pandemics Throughout the History. Cureus 2021;13:e18136. [PubMed]
3. Lippi G, Mattiuzzi C, Henry BM. Uncontrolled confounding in COVID-19 epidemiology. Diagnosis (Berl) 2022;10:200-2. [Crossref] [PubMed]
4. World Health Organization. WHO COVID-19 dashboard. 2024. [accessed December 21]. Available online: https://data.who.int/dashboards/covid19/deaths?n=o
5. Adam D. The pandemic's true death toll: millions more than official counts. Nature 2022;601:312-5. [Crossref] [PubMed]
6. Reyna-Villasmil E, Caponcello MG, Maldonado N, et al. Association of Patients' Epidemiological Characteristics and Comorbidities with Severity and Related Mortality Risk of SARS-CoV-2 Infection: Results of an Umbrella Systematic Review and Meta-Analysis. Biomedicines 2022;10:2437. [Crossref] [PubMed]
7. Pi-Sunyer X. The medical risks of obesity. Postgrad Med 2009;121:21-33. [Crossref] [PubMed]
8. Yang J, Ma Z, Lei Y. A meta-analysis of the association between obesity and COVID-19. Epidemiol Infect 2020;149:e11. [Crossref] [PubMed]
9. Sharma A, Garg A, Rout A, et al. Association of Obesity With More Critical Illness in COVID-19. Mayo Clin Proc 2020;95:2040-2. [Crossref] [PubMed]
10. Cho H, Park Y, Myung SK. Obesity and mortality in patients with COVID-19: A meta-analysis of prospective studies. Asia Pac J Clin Nutr 2024;33:56-65. [PubMed]
11. Haber R, Ghezzawi M, Puzantian H, et al. Mortality risk in patients with obesity and COVID-19 infection: a systematic review and meta-analysis. Metabolism 2024;155:155812. [Crossref] [PubMed]
12. Rossi AP, Gottin L, Donadello K, et al. Obesity as a risk factor for unfavourable outcomes in critically ill patients affected by Covid 19. Nutr Metab Cardiovasc Dis 2021;31:762-8. [Crossref] [PubMed]
13. Sanchis-Gomar F, Lavie CJ, Mehra MR, et al. Obesity and Outcomes in COVID-19: When an Epidemic and Pandemic Collide. Mayo Clin Proc 2020;95:1445-53. [Crossref] [PubMed]
14. Sanchis-Gomar F, Lavie CJ, Neeland IJ, et al. Does abdominal obesity influence immunological response to SARS-CoV-2 infection? Expert Rev Endocrinol Metab 2021;16:271-2. [Crossref] [PubMed]
15. Tong MZ, Sng JD, Carney M, et al. Elevated BMI reduces the humoral response to SARS-CoV-2 infection. Clin Transl Immunology 2023;12:e1476. [Crossref] [PubMed]
16. Madruga MP, Grun LK, Santos LSMD, et al. Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients. Immun Ageing 2024;21:17. [Crossref] [PubMed]
17. van der Klaauw AA, Horner EC, Pereyra-Gerber P, et al. Accelerated waning of the humoral response to COVID-19 vaccines in obesity. Nat Med 2023;29:1146-54. [Crossref] [PubMed]
18. Jang S, Hong W, Moon Y. Obesity-compromised immunity in post-COVID-19 condition: a critical control point of chronicity. Front Immunol 2024;15:1433531. [Crossref] [PubMed]
19. Zhao N, Di B, Xu LL. The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies. Cytokine Growth Factor Rev 2021;61:2-15. [Crossref] [PubMed]
20. Lilov A, Palaveev K, Mitev V. High Doses of Colchicine Act As "Silver Bullets" Against Severe COVID-19. Cureus 2024;16:e54441. [Crossref] [PubMed]
21. Mondeshki T, Mitev V. High-Dose Colchicine: Key Factor in the Treatment of Morbidly Obese COVID-19 Patients. Cureus 2024;16:e58164. [Crossref] [PubMed]
22. Mitev V. Colchicine-The Divine Medicine against COVID-19. J Pers Med 2024;14:756. [Crossref] [PubMed]
23. Khanna D, Khanna S, Khanna P, et al. Obesity: A Chronic Low-Grade Inflammation and Its Markers. Cureus 2022;14:e22711. [Crossref] [PubMed]
24. Lippi G, Plebani M. Cytokine "storm", cytokine "breeze", or both in COVID-19? Clin Chem Lab Med 2020;59:637-9. [Crossref] [PubMed]
25. Saccon TD, Mousovich-Neto F, Ludwig RG, et al. SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner. Nat Commun 2022;13:5722. [Crossref] [PubMed]
26. Fessler SN, Liu L, Chang Y, et al. Body Mass Index Is Associated with Post-Acute Elevations in Biomarkers of Platelet Activation and Inflammation in Unvaccinated Adults Diagnosed with COVID-19 in the Previous 8 Weeks. Obes Facts 2024;17:652-7. [Crossref] [PubMed]
27. Reiterer M, Rajan M, Gómez-Banoy N, et al. Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2. Cell Metab 2021;33:2174-2188.e5. [Crossref] [PubMed]
28. Maurya R, Sebastian P, Namdeo M, et al. COVID-19 Severity in Obesity: Leptin and Inflammatory Cytokine Interplay in the Link Between High Morbidity and Mortality. Front Immunol 2021;12:649359. [Crossref] [PubMed]
29. Pighi L, Lippi G, Mattiuzzi C. The incremental impact of comorbidities in COVID-19-related deaths compared to patients dying from cancer or cardiovascular disease. Egypt J Intern Med 2024;36:78. [Crossref]
30. Zhang X, Ha S, Lau HC, et al. Excess body weight: Novel insights into its roles in obesity comorbidities. Semin Cancer Biol 2023;92:16-27. [Crossref] [PubMed]
31. Honein MA, Christie A, Rose DA, et al. Summary of Guidance for Public Health Strategies to Address High Levels of Community Transmission of SARS-CoV-2 and Related Deaths, December 2020. MMWR Morb Mortal Wkly Rep 2020;69:1860-7. [Crossref] [PubMed]
32. Myers J, Kokkinos P, Cadenas-Sanchez C, et al. Impact of Cardiorespiratory Fitness on COVID-19-Related Outcomes: The Exercise Testing and Health Outcomes Study (ETHOS). Mayo Clin Proc 2024;99:1744-55. [Crossref] [PubMed]