People who have obesity have a significantly increased risk for hospitalization or death from severe infection spanning a wide range of infections, with the highest level of obesity associated with an approximately threefold higher risk for nonfatal and fatal infections and possibly accounting for 1 in 10 infection-related deaths worldwide, new research showed.

“With few exceptions, there was consistent evidence of a dose-response relationship between obesity classes I-III and higher risk of severe infections compared with healthy weight,” reported the authors of the research published in The Lancet.

“The association between obesity and infection risk was observed across subgroups defined by sociodemographic and lifestyle factors, baseline health status, and infection category,” they noted.

Obesity is well known to be linked to a broad range of adverse health effects, and key among them is impaired immunity, which is speculated to play a key role in increasing the risk and severity of infection.

The risk was prominently observed during the COVID pandemic, when a high proportion of those at risk for severe and fatal infection had obesity.

However, studies assessing infection risk across a broad spectrum of infection types, as well as across clinical, socio-demographic and other patient subtypes, have been lacking.

To investigate, the authors conducted a multi-cohort study, looking at pooled data on 67,766 adults in two Finnish cohort studies and 479,498 adults from the UK Biobank database.

Those in the Finnish cohort, assessed between 1998 and 2002, had a mean age of 42 years at baseline and were 73.1% women. Those in the UK cohort, assessed between 2006 and 2010, had a mean age of 57 years, with 54.4% being women. The participants had no recent history of infection-related hospitalizations at baseline.

With an average follow-up of about 13 years, 8230 infections occurred in the Finnish cohorts and 81,945 occurred in the UK Biobank, at a mean age of onset of 50.7 years and 67 years, respectively.

Overall, the pooled analysis showed those with obesity had a 70% greater risk for either fatal or nonfatal severe infection compared with those of healthy weight (hazard ratio [HR], 1.7).

The association increased in a dose-response manner of obesity severity, with the highest risk among those with class III obesity BMI ≥ 40, with a HR of 2.75 in the Finnish cohorts and 3.07 in the UK Biobank cohort.

The higher risks for hospitalization or death were consistent across varying measures of obesity, including BMI, waist circumference, and waist-to-height ratio, as well as in demographic and clinical subgroups, and were importantly also observed among those with or without diabetes and/or metabolic syndrome.

The risks were also consistent across wide-ranging types of infections, including SARS-CoV-2, pneumonia, urinary tract infections, and across nonfatal and fatal, acute and chronic, bacterial and viral (including subtypes), as well as parasitic and fungal infections.

“During the COVID-19 pandemic, people with obesity had a higher risk of being hospitalized or dying with the SARS-CoV-2 infection,” first author Solja T Nyberg, PhD, of the faculty of medicine, University of Helsinki, Helsinki, Finland, told Medscape Medical News.

However, “it is in accordance with our results, that the risk for severe infections is of the same size for nearly all the examined pathogens.”

Two exceptions that did not show a significant link with obesity were severe HIV or tuberculosis, which the authors noted could be explained by reverse causality: In HIV, patients with obesity have been observed to have an absence of adverse wasting effects, while in tuberculosis, weight loss is an indicator of disease progression and underweight impairs immunity.

“These exceptions highlight the context-dependent nature of the relationship between obesity and infection outcomes,” the authors explained.

Obesity a Possible Cause of 1 in 10 Infectious Disease-Related Deaths, but Cautious Interpretation Urged

In applying the data to the context of the 2023 Global Burden of Disease database obesity may have been a causative factor in 0.6 million of 5.4 million deaths, or in about 1 in 10 (10.8%) of deaths in infectious disease worldwide.

“The public health implications of these findings are considerable,” the authors said.

“By combining observed HRs with global and regional data on obesity prevalence and infectious disease mortality, we estimated that 9% to 11% of infection-related deaths worldwide could potentially be prevented by eliminating obesity, rising to 15% during the COVID-19 pandemic.”

The authors urge cautious interpretation of those findings, however, noting the limitation that “data on infection-related deaths and obesity prevalence in the global burden of disease data might be inaccurate, particularly for low-resource countries.”

Mechanisms?

In terms of the specifics of how obesity may increase the risk for severe infections, “broad biological mechanisms may be involved,” said lead author Mika Kivimäki, PhD, chair of Social Epidemiology, University College London, London, England, in a press statement.

“It is plausible that obesity weakens the immune system’s ability to defend against the infectious bacteria, viruses, parasites or fungi, therefore resulting in more serious diseases,” he said.

The authors further specify that immune pathway impairments could include reduced T-cell and NK-cell function, neutrophil dysfunction, and dysregulated complement and adiponectin signaling.

“Overall, these mechanisms point to a generalized susceptibility to worse infectious disease outcomes among individuals with obesity, an assumption that has not yet been robustly evaluated,” they noted.

Weight Loss Linked to Infection Reduction in Other Studies

While the study showed that weight gain from healthy weight or overweight was associated with a modest increase in infection risk, weight loss from obesity to overweight or healthy weight reduced the risk for infection (HR, 0.8), although not to the level of the persistent healthy-weight group.

Previous studies have further shown weight loss to be associated with a reduction in infections.

They include the SELECT trial of the GLP-1 drug semaglutide, conducted during the COVID pandemic and enrolling more than 17,000 patients with overweight or obesity and cardiovascular disease but no diabetes. That study showed treatment with the therapy over 3.3 years to be associated with reduced all-cause mortality, partly due to fewer infection-related deaths.

Importantly, if those results are further confirmed in the ongoing SURPASS-CVOT trial comparing tirzepatide with dulaglutide in individuals with type 2 diabetes and cardiovascular disease, “this would further strengthen the evidence for causality, suggesting that obesity prevention and weight reduction achieved through widely used pharmacotherapies could lower infection-related mortality,” the authors asserted.

In addition to the use of observational data that cannot confirm causality, key study limitations include that the Finnish and UK cohorts are not necessarily representative of the general population.

Nevertheless, the study indicates that “obesity should receive greater attention in public health strategies aimed at preventing severe infections,” Nyberg said. “Effective prevention of adiposity, implementation of evidence-based weight-loss interventions, and stronger integration of obesity considerations into vaccination programs for high-risk groups could help reduce the burden of severe infections and related mortality,” she said.

Study Addresses Evidence Gaps

Commenting on the study, Iain M. Carey, PhD, a senior lecturer in epidemiology in the Population Health Research Institute, City St. George’s School of Health and Medical Sciences, University of London, London, England, said the study adds important new insights.

“The new findings are quite significant as they address evidence gaps around obesity and the risk of serious infections and estimate the impact globally,” Nyberg told Medscape Medical News.

Of note, in research published in 2025 in the International Journal of Obesity, Carey and his colleagues also found an increased risk for infection among people with type 2 diabetes — independent of their weight.

“The pattern is such that at every level of BMI, including normal weight, people with type 2 diabetes are at a higher risk of infections than people without type 2 diabetes,” he explained.

Together, the findings underscore that “the relationship between BMI level and infection risk appears to act independently of type 2 diabetes,” he said.

Carey agreed that the collective findings indicate “there is a need for a greater awareness of the higher infection risk that obesity carries amongst both clinicians and people living with obesity.” 

Further commenting, Michaela R. Anderson, MD, an assistant professor of medicine (pulmonary, allergy, and critical Care) at the Hospital of the University of Pennsylvania, Philadelphia, added that, while obesity is commonly considered a risk factor for cardiovascular disease, “a growing body of evidence [shows] that obesity is also a risk factor for more severe manifestations of respiratory infections.”

“This study builds on that by establishing that obesity is a risk factor for severe manifestations of infections more broadly,” she told Medscape Medical News. “These results underscore that preventing and treating obesity is critical not only for reducing cardiovascular mortality but also likely for lowering the risk of infection-related deaths.”

In terms of clinical implications: “This means that even in your well-controlled patients with diabetes, obesity will independently increase risk of severe manifestation of an infection,” Anderson noted.

“[Additionally], vaccination is particularly important in patients with obesity to further decrease risk of severe manifestation of infection,” she said.

Finally, “clinicians should consider discussing overall risk of infection when discussing anti-obesity treatments with patients.”

This study was funded by Wellcome Trust, Medical Research Council and Research Council of Finland. Nyberg, Carey, and Anderson had no disclosures to report.