Information from major international cohort studies indicates that excessive body fat may heighten susceptibility to severe infections and significantly contribute to the overall global death toll from infectious diseases, thus underscoring prevention as a crucial public health imperative.
In a recent publication in The Lancet, researchers investigated whether adiposity in adults elevates the likelihood of serious infections and quantified its global contribution to infection-related mortality.
Close to one in eight adults worldwide struggles with obesity, yet its impact extends beyond just diabetes and cardiovascular ailments. During the COVID-19 pandemic, individuals with obesity frequently exhibited higher rates of disease severity and in-hospital mortality. The question remains: is this vulnerability confined to respiratory viruses, or does excess weight also increase the risk across a broader spectrum of infectious diseases?
It is established that obesity compromises the general immune system, promotes a state of chronic inflammatory change, and disrupts metabolic homeostasis, developments that could heighten infection risk and potentially lead to more severe infectious outcomes. While this is biologically plausible, the evidence linking it to diverse infections is less comprehensive. Further research is needed to fully elucidate how body weight affects infection risk across different individuals and various contexts.
This prospective, multi-cohort study integrated individual-level data from the Finnish Public Sector Study and the Health and Social Support Study in Finland, with replication in the UK Biobank. Data were utilized to establish baseline Body Mass Index (BMI) measurements spanning 1998 to 2010, incorporating both self-reported and measured values. Three BMI classifications were used: normal weight (BMI 18.5–24.9 kg/m²), overweight (BMI 25.0–29.9 kg/m²), and obesity (BMI >30.0 kg/m²). The obesity group was further stratified into three classes: Class I (30.0–34.9 kg/m²), Class II (35.0–39.9 kg/m²), and Class III (≥40.0 kg/m²). Participants’ waist circumference and waist-to-height ratio were also assessed.
Individuals with prior history of severe infections were excluded from the analysis. National hospitalization and mortality registers were employed for follow-up to identify the first occasion of a severe infection, defined as any infection managed with inpatient care or resulting in death, rather than less severe, outpatient-treated episodes. In total, 925 infectious disease diagnoses were categorized by pathogen type and the chronic nature of the illness.
Cox proportional hazards regression models were constructed, adjusted for age, sex, socioeconomic status, smoking, alcohol intake, physical activity, glucocorticoid use, hypertension, metabolic syndrome, diabetes, cardiometabolic diseases, respiratory illnesses, cancer, and depression. Hazard ratios were then combined with data on obesity prevalence and mortality derived from the Global Burden of Disease, Injuries, and Risk Factors (GBD) study to estimate population attributable fractions of infection-related deaths globally.
The Finnish cohort comprised 67,766 adults (mean age 42 years), while the UK Biobank included 479,498 adults (mean age 57 years). Over follow-up periods exceeding a decade, 8,230 cases of severe infection were identified in Finland and 81,945 in the UK.
A clear ‘dose-response’ relationship emerged; compared to normal-weight individuals, those classified as having Class III obesity faced nearly three times the risk of infection-related hospitalization or death. The hazard ratio for severe infections associated with Class III obesity was 2.69 in Finland and 3.07 in the UK Biobank. All grades of obesity were linked to an overall approximate 30–40% higher risk of severe infections compared to normal-weight individuals, with substantially elevated risks seen in the most severe obesity categories.
This association remained robust even after controlling for lifestyle factors, socioeconomic status, and underlying health conditions. A comparable increase in risk was observed when assessing obesity using measurements of waist circumference and waist-to-height ratio. These findings suggest consistent links across different indicators of adiposity, rather than similar levels of risk across disparate measurement methods.
Obesity amplified the risk across nearly all infection categories. A notably stronger association was found with viral infections, particularly acute viral infections. Bacterial infections, encompassing both invasive and localized forms, were also more frequent among obese individuals. The highest association was noted with skin and soft tissue infections, where the risk nearly tripled. In the UK Biobank cohort, the hazard ratio specifically for COVID-19 was 2.3. Conversely, no elevated risk was detected for HIV or tuberculosis, likely reflecting reverse causality due to weight loss associated with these chronic diseases.
Analysis of weight changes further corroborated these findings. Individuals who gained weight, moving from overweight to obese status, exhibited a heightened infection risk, whereas those who lost weight, transitioning from obese to overweight or normal weight, showed a moderate reduction in risk.
Applying the hazard ratios to global GBD data suggested that approximately 8.6% of infection-related deaths in 2018, 15.0% in 2021, and 10.8% in 2023 were attributable to adult obesity. In raw figures, around 0.6 million infection-related fatalities worldwide in 2023 were linked to obesity. The largest proportion of such deaths was found in North Africa and the Middle East, and the smallest in South Asia.
Adult obesity represents a significant and persistent risk factor for severe infections caused by diverse pathogens and affecting various populations. The risk increases progressively with the severity of obesity and persists even after accounting for lifestyle and existing morbidity.
Roughly one in ten infection-related deaths globally is connected to adult obesity, not merely overweight status, indicating obesity’s influence on both infectious disease morbidity and non-communicable diseases. Therefore, preventing obesity, implementing evidence-based weight management programs, and designing vaccination and infection control policies that specifically address obesity are of paramount importance.
Addressing obesity will contribute to reducing hospitalizations, mortality, and the burden on healthcare systems during typical infectious disease seasons and future pandemics alike. However, as this study is observational and based on specific population cohorts, the findings do not establish causation, and the global estimates rely on modeling assumptions that may vary regionally. Furthermore, the cohorts are not perfectly representative of the wider population, and residual confounding influences cannot be entirely ruled out, meaning absolute risk estimates might differ in other populations.
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