Severe infections added to list of obesity-related comorbidities

Adults with obesity are at increased risk of infection-related hospitalizations and mortality, with a 10th of infection-related deaths estimated to be attributable to obesity, according to a study.

Pooled data from two Finnish cohort studies showed that the risk of severe infections rose in a dose-response manner across BMI categories, with the highest risk increase observed among individuals with class III obesity. Compared with healthy weight, class III obesity was associated with up to a threefold increase in the risk of nonfatal severe infections (hazard ratio [HR], 2.75, 95 percent confidence interval [CI], 2.24–3.37), fatal infections (HR, 3.06, 95 percent CI, 1.25–7.49), or either outcome (HR, 2.69, 95 percent CI, 2.19–3.30). [Lancet 2026;407:951-962]

These findings were replicated in the UK Biobank cohort, in which individuals with class III obesity had a more than threefold higher risk of nonfatal severe infections (HR, 3.07, 95 percent CI, 2.95–3.19), fatal infections (HR, 3.54, 95 percent CI, 3.15–3.98), or either outcome (HR, 3.07, 95 percent CI, 2.95–3.19) compared with those who had healthy weight.

The association between obesity and the risk of severe infections was consistent across different indicators of obesity (BMI, waist circumference, and waist-to-height ratio), demographic and clinical subgroups (including those defined by diabetes or metabolic syndrome status), and a wide range of infections (nonfatal and fatal, acute and chronic, bacterial and viral, and parasitic and fungal). No associations were observed for HIV (which accounted for 8.8 percent of all persistent nonherpes viral infections) or tuberculosis (which accounted for 71.5 percent of all mycobacterial infections).

“In repeat-measure analyses, weight gain from healthy weight or overweight was associated with a modest increase in infection risk, whereas weight loss from obesity was linked to a modest reduction in risk,” according to first study author Dr Solja Nyberg from the University of Helsinki, Helsinki, Finland, and colleagues.

When these risk estimates were applied to global burden of disease data, the percentages of infection-related deaths attributable to obesity were estimated at 8.6 percent in 2018, 15 percent in 2021, and 10.8 percent in 2023.

“The public health implications of these findings are considerable… We estimated that 9 percent to 11 percent of infection-related deaths worldwide could potentially be prevented by eliminating obesity (rising to 15 percent during the COVID-19 pandemic),” Nyberg and colleagues said.

“If results from the GLP-1RA trials are 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,” they added.

Does a healthy state of obesity exist?

In an accompanying editorial, Drs Thorkild Sørensen and Merete Osler from the University of Copenhagen, Copenhagen, Denmark, highlighted the consistency of the findings across multiple risk strata, especially those presumably associated with resistance to infections, as a striking feature of Nyberg and colleagues’ work. This indicates that the risk increase for severe infections is present irrespective of cardiometabolic complications, abdominal obesity (measured by waist or waist-to-height ratio), or glucocorticoid treatment, Sørensen and Osler noted. [Lancet 2026;407:916-917]

“These findings challenge the current contention of obesity as being in a so-called healthy or unhealthy state regarding development of metabolic aberrations possibly interfering with the strength of the immune defence,” they wrote. [Obes Rev 2021;22:e13216]

However, the study missed the opportunity to look at an obesity group consisting of individuals who did not develop the above-mentioned features during the follow-up period. Sørensen and Osler noted that such a group could have a lower risk of infection irrespective of the presence of obesity.

It is also possible that individuals who were possibly in a healthy state of obesity at baseline might have progressed to the unhealthy state during the follow-up, they added. “Therefore, the question remains whether such a safe state of excess fat mass exists, without an increased comorbidity risk, now also including risk of infections.

“Whatever the explanations are of obesity–infection associations, the study … provides an impetus for more research and is a valuable source of quantitative information on the burden of both obesity and communicable diseases. With the expected rapid development of the global pandemic of obesity, the burden of obesity-related communicable diseases will be of increasing concern, both in public health settings and in clinical management in either disease domain,” Sørensen and Osler concluded.

The current study included 67,766 participants from the Finnish cohorts (mean age at baseline 42.1 years, 73.1 percent female, 42.2 percent overweight or obese) and 479,498 participants from the UK Biobank (mean age at baseline 57 years, 54.4 percent female, 67 percent overweight or obese).

A total of 8,230 incident infection cases in the Finnish cohorts and 81,945 in UK Biobank were recorded over a mean follow-up of 14.1 and 12.6 years, respectively.