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Table 1 Study Goals and Features Intended to Address Specific Knowledge Gaps

From: Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

Knowledge Gap Study Feature
1. Description of the frequency of influenza virus infection among healthcare personnel, including those manifesting as acute respiratory illness, atypical illness, or asymptomatic infection
 Studies of influenza illness among HCP using laboratory-confirmed outcomes are scarce. Identification of symptomatic influenza virus infections with mqRT-PCR assay.
 Typical surveillance strategies have focused on acute respiratory illness using highly specific case definitions which overlook non-respiratory and non-febrile manifestations of influenza disease. Usage of a broad case definition: “illness with cough, runny nose, body aches, or feverishness in the past seven days.”
 Few studies have used both molecular and serologic diagnostics to assess the total burden of influenza virus infection among HCP. In addition to mqRT-PCR, 4-fold increases in HI from pre- to post-season will also be used to identify possible influenza virus infection among unvaccinated HCP.
 It is unclear how differences in sex, age, occupation, and underlying health may contribute to the frequency of influenza illness among HCP. Usage of random stratified sampling to enroll a mixture of HCP by sex, age, and occupation. Assess underlying health status by self-report and medical record extraction.
 Further research is needed on whether specific HCP roles and responsibilities increase the risk of infection with influenza and other respiratory pathogens. Comparison of the frequency of ARFI (and infection with influenza and other respiratory viruses) by number of hours of direct patient care and by performance of aerosol-generating procedures (such as suction of fluids and tracheal intubation).
 More information is needed on the impact of influenza illness on HCP’s absence from work due to illness and working while ill. Assessment of the duration of illness, missed, and rescheduled work due to illness, hours worked during illness, and ability to do usual activities.
2. Identification of predictors of vaccine acceptance (and hesitancy)
 Most studies of HCP have focused on influenza vaccine uptake in specific seasons and less on behavior over multiple years. Description of how the frequency of influenza vaccination during the five years prior to enrollment and during the two to three years of participation in the cohort varies by sex, age, occupation, and socio-economic status.
 Most studies of KAP associated with influenza vaccination among HCP have been conducted in the United States or Western European countries. This study is conducted in Israel, and will examine KAP topics including association between frequency of vaccination and perceived susceptibility to influenza, perceived benefits and risks of influenza vaccination, readiness to be vaccinated, and anticipated worry and regret about influenza vaccination decisions.
3. Examination of how repeated influenza vaccination may modify immunogenicity
 Few studies have assessed the effects of repeated influenza vaccination across multiple seasons on immunogenicity. Examination of how HI differs depending on the receipt of influenza vaccines up to ten years prior to the study for consistent health plans members.
 Further research is needed on the mechanisms through which prior vaccination affects immunogenicity. Examination of whether any link between repeated vaccination and HI can be explained by HCP’s “antibody landscape”.
 Further research is needed on whether repeated prior vaccination impacts cell mediated immune response to influenza vaccines. In a subset of participants who provide peripheral blood mononuclear cells before and after vaccination, examination of whether repeated prior vaccination is associated with suppression of B-cell and T-cell immunogenicity.
4. Evaluation of influenza vaccine effectiveness in preventing influenza illness and associated missed work and working while ill
 Prior study of IVE among HCP used serologic outcomes, which are likely biased among vaccinees. Estimate the effectiveness of the influenza vaccine in preventing mqRT-PCR confirmed influenza illness among HCP.
 It is unclear whether influenza vaccines may reduce missed work due to influenza illness or reduce time spent working while ill (i.e., presenteeism) with influenza. Examine the hours of missed work and presenteeism between the dates of onset and resolution of influenza illness; apply these observations to estimate potential IVE in averting missed work or presenteeism.
 More information is needed on the extent to which prior vaccination may offer residual protection and/or interfere with IVE in subsequent seasons. Examination of IVE associated with combinations of current season vaccination and frequent vs. infrequent prior vaccinations.
 Further research is needed on whether the influenza vaccination may modify influenza disease severity and duration among those who become infected despite vaccination. Among HCP with influenza illness, examination of whether symptom severity and illness duration are lower among vaccinated vs. unvaccinated HCP.
  1. Abbreviations: HCP healthcare personnel, mqRT-PCR multiplex quantitative real-time reverse transcription polymerase chain reaction, HI hemagglutination inhibition, ARFI acute respiratory illness or febrile illness, KAP knowledge, attitudes, and practices, IVE influenza vaccine effectiveness