The Relationship Between the Severity of Influenza-Related Illness and Timing of Seasonal Influenza Vaccination in Hospitalized Children and Adults Identified Through FluSurv-NET, 2013-2017 Open Access

Abstract

Background: The burden of influenza in the United States is substantial, and influenza vaccine is known to prevent complications of influenza. There has been growing concern that protection provided by the seasonal influenza vaccine may wane throughout an influenza season. This analysis seeks to determine whether timing of influenza vaccine is associated with odds of severe outcomes, including admission to the intensive care unit (ICU), death, pneumonia, and prolonged hospitalization among children and adults with influenza-related hospitalization. 

Methods: We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET) and included patients ≥6 months of age hospitalized with laboratory-confirmed influenza during October 1-April 30 of influenza seasons 2013-14 through 2016-17 who received seasonal influenza vaccine ≥14 days prior to admission. Demographic differences among those who received vaccine early versus late were compared using Chi-square. Multivariate logistic regression was used to model the relationship between timing of vaccine and dichotomous outcomes, and Cox proportional hazard modeling was used to describe time-to-event outcomes. All analyses were stratified by age group and influenza type/subtype.

Results: Among 21,306 adults and 1,728 children, early vaccine receipt was associated with older age (p<0.0001), white race (p<0.0001), and certain medical conditions including cardiovascular disease, metabolic disorder, and kidney disease (p<0.001) in adults, and multiple conditions in children. Children were more likely to have ICU admission than adults (22.2% among children; 10.2% ≥85 years of age), and death increased with age among adults. Odds of ICU admission, death, and pneumonia were not increased in those with longer time between vaccination and hospitalization. Notably, odds of death decreased in adults as time since vaccination increased (aOR 0.528, 95% CI 0.369, 0.756 comparing those with ≥150 days since vaccination to those with 14-59 days). Duration of hospitalization was not associated with timing of vaccine in most groups. 

Conclusion: Among influenza-vaccinated children and adults hospitalized with influenza, multiple demographic characteristics were associated with timing of influenza vaccination. However, prolonged time between vaccination and hospitalization was not associated with increased odds of death, ICU admission, pneumonia, or prolonged hospitalization. This data supports current recommendations to receive vaccine by the end of October annually. 

Table of Contents

INTRODUCTION ................................................................................................................................... 1

BACKGROUND ...................................................................................................................................... 3

METHODS ............................................................................................................................................... 7

Aims and Hypotheses ............................................................................................................................ 7

Study Design, Setting, and Population .................................................................................................. 7

Influenza Vaccination Date ................................................................................................................... 8

Measurements – Predictor, Outcomes, and Covariates ......................................................................... 9

Sample Size/Power Considerations ..................................................................................................... 11

Analytic Plan ....................................................................................................................................... 12

RESULTS ............................................................................................................................................... 15

Description of Cohorts and Seasons .................................................................................................... 15

Timing of Vaccine Receipt Among Adults ......................................................................................... 15

Timing of Vaccine Receipt Among Children ...................................................................................... 16

Association Between Timing of Vaccination and Severe Outcomes Among Adults ......................... 16

Association Between Timing of Vaccination and Severe Outcomes Among Children ...................... 17

Sensitivity Analyses ............................................................................................................................ 18

DISCUSSION ......................................................................................................................................... 20

REFERENCES ...................................................................................................................................... 26

TABLES AND FIGURES ..................................................................................................................... 31

Figure 1: Flowchart of included/excluded cases of patients hospitalized with influenza in the United

States identified through FluSurv-NET, 2013-2017 ............................................................................ 31

Table 1: Characteristics of adults hospitalized with influenza-related illness during the 2013-2014

through 2016-2017 influenza seasons, by timing of vaccine administration ...................................... 32

Table 2: Prevalence of ICU admission and death and mean duration of hospitalization among adults

with influenza-related hospitalization, by age group and influenza type/subtype .............................. 34

Table 3: Relationship between time since vaccination and severe outcomes in adults hospitalized with

influenza-related illness, overall and by age group ............................................................................. 35

Table 4: Relationship between time since vaccination and risk of ICU admission and death in adults

hospitalized with influenza-related illness, by influenza type/subtype ............................................... 36

Table 5: Characteristics of children hospitalized with influenza-related illness during the 2013-2014

through 2016-2017 influenza seasons, by timing of vaccine administration ..................................... 37

Table 6: Prevalence of ICU admission and pneumonia and mean duration of hospitalization among

children with influenza-related hospitalization, by age group and influenza type/subtype ................ 39

Table 7: Relationship between time since vaccination and severe outcomes in children hospitalized

with influenza-related illness, overall and by age group ..................................................................... 40

Table 8: Relationship between time since vaccination and risk of ICU admission and pneumonia in

children hospitalized with influenza-related illness, by influenza type/subtype ................................. 41

Table 9: Sensitivity analyses for adults to assess misclassification of exposure ................................ 42

Table 10: Sensitivity analyses for children to assess misclassification of exposure .......................... 43

Supplemental Table 1: Association between patient characteristics and severe outcomes among

adults hospitalized with laboratory-confirmed influenza during the 2013-2014 through 2016-2017

influenza seasons ................................................................................................................................. 44

Supplemental Table 2: Association between patient characteristics and severe outcomes among

children hospitalized with laboratory-confirmed influenza during the 2013-2014 through 2016-2017

influenza seasons ................................................................................................................................. 47

Supplemental Table 3: Examining changes in odds of ICU admission and death in adults, excluding

patients with <28 days between vaccination and hospitalization ........................................................ 50

APPENDIX ............................................................................................................................................. 51

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery Health Sciences, Epidemiology
Keyword	Influenza Vaccine
Committee Chair / Thesis Advisor	Evan Anderson, MD, Emory University
Committee Members	Christina Rostad, MD, Emory University Matthew Magee, MPH, PhD, Emory University

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