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Randomized Controlled Trial
. 2026 Jul 16:14:1874186.
doi: 10.3389/fpubh.2026.1874186. eCollection 2026.

Assessing the relationship between body mass index and influenza-like illness risk and symptom severity among military health system beneficiaries vaccinated against influenza: a pooled prospective cohort study from a randomized trial

Mofan Gu  1   2 , Stephanie A Richard  1   2 , Rhonda E Colombo  1   2   3   4 , Kat Schmidt  1   2 , Anuradha Ganesan  1   2   5 , Wesley R Campbell  5 , Katrin Mende  1   2   6 , Srihari Seshadri  7 , Adam Saperstein  8 , David E Hrncir  7   9   10 , Ryan C Maves  3   11 , Robert J O'Connell  1 , Christina E Spooner  7 , Mark P Simons  1 , Laurie A Housel  7   12 , Alan Williams  8 , John H Powers 3rd  13 , Anthony Fries  14 , Christian L Coles  1   2 , Timothy H Burgess  1   3 , Simon D Pollett  1   2
Affiliations
Randomized Controlled Trial

Assessing the relationship between body mass index and influenza-like illness risk and symptom severity among military health system beneficiaries vaccinated against influenza: a pooled prospective cohort study from a randomized trial

Mofan Gu et al. Front Public Health. .

Abstract

Introduction: Obesity prevalence is rising globally and associated with increased influenza mortality. The relationship between obesity and influenza-like-illness (ILI) incidence and symptom severity is less clear.

Materials and methods: US Military Health System (MHS) beneficiaries enrolled in a randomized influenza vaccine trial received one of three influenza vaccines and were followed for ILI via weekly surveys throughout one influenza season. Participants were pooled across vaccine arms into a prospective cohort. We compared ILI risk and ILI symptom severity (Flu-PRO) across body mass index (BMI) categories using multivariable regression models.

Results: Among the 8,334 participants with >50% response rates to weekly ILI surveys, 42% had an overweight-range BMI and 24% had an obesity-range BMI. The median age was 36.2, and 86% had no baseline comorbidities. Over one quarter of the participants (27%) reported at least one ILI during follow-up, with a median duration of 11 days. Participants with an overweight and obesity-range BMI were more likely to report ILIs [adjusted incidence rate ratio (aIRR) 1.18 (95% confidence interval (CI): 1.05-1.33) and 1.59 (95% CI: 1.37-1.84), respectively]. Participants with obesity also had higher risks of reporting moderate-to-severe symptoms in four Flu-PRO domains: gastrointestinal, respiratory, systemic, and throat [adjusted risk ratio (aRR) of 1.64 (95% CI: 1.01-2.70), 1.33 (95% CI: 1.05-1.67), 1.32 (95% CI: 1.06-1.63), and 1.20 (95% CI 1.02-1.40) respectively].

Conclusions: Higher BMI was associated with ILI incidence and severity. These findings prompt further research into optimal strategies to reduce the impact of ILI in MHS settings and the general population.

Keywords: body mass index; influenza; influenza-like illness; military health; obesity.

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Conflict of interest statement

RM has received research funding from Merck, GeoVax, Biotest, AiCuris, and has been paid as a consultant by GSK and Shionogi. WC, DH, LH, AS, AF, AW, CS, SS, RO'C, MS, and TB are service members or employees of the US Government. This work was prepared as part of their official duties. Title 17 USC. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 USC §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties. Mention of trade names, commercial products, or organizations does not imply endorsement by the US Government. MG, SR, RC, KS, AG, KM, CC, and SP were employed by The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. The remaining author(s) declared that this work 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
Flow diagram of participant selection and analytic outcomes in PAIVED study participants who reported BMI information and had a survey response rate of 50% and higher (n = 8,334). The endpoints and methods of assessments for ILI (incidence, illness duration, and symptom severity) and underlying lab-confirmed pathogens (including influenza subtypes) are depicted.
Figure 2
Figure 2
Adjusted associations between BMI category and (A) moderate-to-severe ILI symptom severity measured by Flu-PRO and (B) lab-confirmed respiratory virus infection, using normal/underweight BMI as the reference group. Risk ratios (aRR) were estimated using Poisson regression with robust variance, and odds ratios (aOR) were estimated using logistic regression. Each model was adjusted for confounders identified via directed acyclic graphs. Analyses of lab-confirmed infections were performed separately for each virus type; parsimonious models were used for lab-confirmed influenza, adenovirus, bocavirus, HMPV, PIV, and RSV. Adenovirus and bocavirus were excluded due to small case numbers. BMI, body mass index; Flu-PRO, influenza patient-reported outcome; HMPV, human metapneumovirus; PIV, parainfluenza virus; RSV, respiratory syncytial virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
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