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

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.

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.

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.

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.