Influenza-like illness in cigarette smokers and electronic-cigarette users: a secondary analysis from the PAIVED study

Background: The Pragmatic Assessment of Influenza Vaccine Effectiveness in the Department of Defense (PAIVED) study was a clinical trial of three influenza vaccines in military beneficiaries enrolled at 10 military treatment facilities over four influenza seasons (2018/19-2021/22). This secondary analysis aimed to assess the relationship between cigarette smoking and e-cigarette use and influenza-like illness (ILI) incidence and severity. Methods: Demographic information, including cigarette smoking and e-cigarette use, was collected at enrollment. ILIs were identified during the influenza season of enrollment using weekly surveys. ILI symptoms were reported using the inFLUenza Patient-Reported Outcome (FLU-PRO) instrument. The relationship between smoking status and risk of reporting an ILI was estimated using Poisson regression; ILI severity was compared by cigarette smoking and e-cigarette use using multivariable linear regression. Results: Among 8,708 participants with cigarette smoking status, 4.3% were current smokers and 11.9% were former smokers. Current cigarette smokers reported higher respiratory domain scores (0.24 (95% CI: 0.07, 0.41)) than non-smokers; former cigarette smokers were at higher risk of reporting an ILI than non-smokers [rate ratio 1.11 (95% CI: 1.02, 1.20)] and reported ILI episodes that were on average 1.23 days longer in duration (95% CI: 0.29, 2.17). Among 8,119 participants with e-cigarette use status, 3.9% were current users and 2.6% were former users. Current e-cigarette users reported more than one additional day with limited activity (1.14 days, 95% CI: 0.10, 2.18) and 0.78 additional days with fever (95% CI, 0.20, 1.35); former e-cigarette users were at higher risk of reporting an ILI than nonusers [rate ratio 1.20 (95% CI, 1.04, 1.38)] and reported higher respiratory domain scores than non-users (0.27 (95% CI 0.08, 0.46)). Conclusion: We observed slightly higher ILI risk in former cigarette smokers and e-cigarette users, longer symptom duration in former cigarette smokers, and higher respiratory symptom scores in current cigarette smokers and former e-cigarette users compared to non-smokers/users. Findings in this secondary analysis are exploratory and hypothesis-generating; additional studies are needed to confirm the relationships reported here.