Accounting for Potential Unmeasured Confounding in the Association between Influenza vaccination and COVID-19 Hospitalization: Sensitivity Analysis Using E-value Method

Document Type : Original Article


1 Department of Public Health, Sirjan School of Medical Sciences, Sirjan, Iran

2 Department of Public Health Sciences. Neyshabur University of Medical Sciences, Neyshabur, Iran

3 Modeling in Health Research Center, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran

4 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

5 Sirjan School of Medical Sciences, Sirjan, Iran

6 National Program for Malaria and Vector Borne disease control, Center of Disease Control & Prevention, Ministry of Health and Medical Education, Tehran, Iran

7 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

8 Department of Epidemiology, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran.


Background: Unmeasured confounding is the primary obstacle to causal inference in observational research. We aimed to illuminate the association between exposure to influenza vaccination (IV) within six months before contracting the coronavirus disease (COVID-19) and COVID-19 hospitalization in relation to unmeasured confounding using the E-value method.
Materials and Methods: Information about 367 patients, 103 of whom (28.07 %) had received IV, and confounders included sex, age, occupation, cigarette smoking, opium, and comorbidities were collected. We estimated the interest association using the inverse probability weighted (IPW) method. There was no information on some potential unmeasured confounders, such as socio-economic status. Therefore, we computed E-value as a sensitivity analysis, which is the minimum strength of unmeasured confounding to explain away an exposure-outcome association beyond the measured confounders completely.
Results: IPW denoted 1.12 (95% CI: 0.71 to 1.29) times greater risk of COVID-19 hospitalization in patients exposed to IV than in unexposed individuals. Sensitivity analysis demonstrated that an E-value (95% CI) of 1.49 (1.90 to 2.15) is required to shift the RR and the corresponding confidence Interval (CI) lower and upper limits toward the null. Moreover, if they had been omitted, the most computed E-values for measured confounders were relatively larger than for unmeasured confounders.
Conclusion: According to the context of the measured confounders, if they had been omitted, an E-value of 1.16 to 1.76, a weaker confounding could fully explain away the reported association, suggesting that no relationship exists between IV and COVID-19 hospitalization.