Marshfield Clinic Research Institute

Interim Estimates of 2022─23 Influenza Vaccine Effectiveness from 

Two Studies in Wisconsin: A Test-Negative Case-Control Study and a 

Community Cohort Study

ACIP Meeting | February 22, 2023

Huong McLean presenting on behalf of the study team

Marshfield Clinic Research Institute received support for this study from CSL Seqirus and CDC 

(75D30120C09259) 
Test-negative case-control study

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• Enrollees: Outpatients aged 6 months – 64 years with acute respiratory illness 

with cough ≤7 days duration

• Dates of enrollment: December 2, 2022 – February 10, 2023

• Nasal and oropharyngeal swabs tested for influenza and SARS-CoV-2 

• Vaccination status: documented (in health record) receipt ≥14 days before 

illness onset per ACIP recommendations 

• Analysis: VE = (1 – adjusted OR) x 100%

‒ Logistic regression model adjusted for age, month of onset, higher-risk condition 

(self report)

Methods: Test-negative case-control study

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RT-PCR results by week of enrollment 

4 1 patient was positive for both influenza and SARS-CoV-2 and represented above as separate counts (week ending 12/24/2022) 

• 34/34 sequenced A(H3N2) 

viruses belonged to 

subclade 2a2

• 9/9 A(H1N1pdm09) 

belonged to subclade 5a.2 
Participant* characteristics

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Total no. of 

patients

No. (%) 

vaccinated†

No. (%) 

influenza positive

No. (%) influenza- and 

SARS-CoV-2 negative

Total 545 186 (34) 116 (21) 249 (79)

Age 6 mos – 17 years 223 69 (31) 42 (19) 181 (81)

18 – 64 years 322 117 (36) 74 (23) 248 (77)

Sex Female 318 127 (40) 65 (20) 253 (80)

Male 227 59 (26) 51 (22) 176 (78)

Race/ethnicity Non-Hispanic White 482 161 (33) 105 (22) 377 (78)

Hispanic 35 12 (34) 6 (17) 29 (83)

Non-Hispanic non-White 28 13 (46) 5 (18) 23 (82)

Self report of higherrisk condition§

Yes 154 69 (45) 30 (19) 124 (81)

No 391 117 (30) 86 (22) 305 (78)

Self report of ≥2 COVID19 vaccine doses 

Yes 258 133 (52) 51 (20) 207 (80)

No 287 53 (18) 65 (23) 222 (77)

*109 patients had a positive test result for SARS-CoV-2 virus infection and were excluded.

†84% received cell-culture based vaccine (ccIIV4). 

§Based on self-report of asthma or another chronic lung disease, cancer, diabetes, heart disease including high blood pressure, immunocompromising 

condition, kidney disease, liver disease, obesity, and pregnancy in the 12 months preceding enrollment.
Vaccine effectiveness (VE) against outpatient influenza, 

children and adults aged 6 months – 64 years

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Influenza positive Influenza- and 

SARS-CoV-2 negative Adjusted VE*

No. vaccinated / 

Total % No. vaccinated / Total % % (95% CI)

Influenza A 26 / 116 22 160 / 429 37 54 (23-73)

A(H3N2) 16 / 86 19 160 / 429 37 60 (25-79)

Study period: December 2, 2022 – February 10, 2023.

*VE was estimated using the test-negative design as 100% x (1 – aOR) where aOR represents ratio of odds of being vaccinated among influenza positive 

cases to odds of being vaccinated among influenza-negative and SARS-CoV-2-negative controls; ORs were estimated using logistic regression with 

adjustment for age, month of illness onset, and presence of one or more higher-risk condition. 
Prospective community cohort study

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• Ongoing community cohort in central Wisconsin

• 241 children aged 1 – 17 years followed weekly since September 5, 2022

• Weekly reporting for absence or presence of symptoms

 Fever, cough, loss of smell or taste, sore throat, muscle/body aches, shortness of breath, 

diarrhea, nasal congestion/runny nose, or nausea/vomiting

• New symptom onset prompts self- or guardian-collection of anterior nasal 

swab for influenza and SARS-CoV-2 testing 

• Information collected from surveys and extracted from electronic health 

records (e.g., vaccination history, clinical influenza test results)

Methods: Community cohort study

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• Influenza case: positive RT-PCR influenza result (research or clinical sample)

• VE = 11 − aaaaaaaaaaaaaaaa HHRRrrrrrrrr oooo iiii iiii iiii iiii ii ii ii aa aa vv vv pp pp −

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∗ 1111111

• Adjusted for age, higher-risk condition (self-report), COVID-19 vaccination 

Analysis: Community cohort study

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At risk October 23, 2022 – February 10, 2023 or positive influenza infection date

Vaccinated ≥14 days after influenza vaccine receipt*

Unvaccinated Time before influenza vaccination

Censored Person-time for the 13 days after vaccine receipt

Cox proportional hazards model with time-varying vaccination status

*Based on documentation in health record according to ACIP recommendations 
Characteristics of community cohort

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Total no. of 

participants*

No. (%) 

vaccinated†

No. (%) 

influenza positive¶

Total 241 94 (39) 34 (14)

Age 1 – 8 years 71 31 (44) 9 (13)

9 – 17 years 170 63 (37) 25 (15)

Sex Female 116 49 (42) 17 (15)

Male 125 45 (36) 17 (14)

Race/ethnicity Non-Hispanic White 233 92 (39) 33 (14)

Hispanic 2 2 (100) 1 (50)

Non-Hispanic non-White 6 0 (0) 0 (0)

Self report of higher-risk

condition§

Yes 31 13 (42) 6 (19)

No 210 84 (39) 28 (13)

≥2 COVID-19 vaccine doses Yes 115 61 (53) 20 (17)

No 126 33 (26) 14 (11)

*242 participants enrolled; 1 was excluded because they were partially vaccinated per ACIP recommendations prior to the start of the analysis period.

†84% received cell-culture based vaccine (ccIIV4). 

¶3 cases occurred ≤14 days from influenza vaccination and were censored at the time of vaccination. 

§Based on self-report of asthma, immunocompromised state, serious heart condition, or other chronic lung disease.
Influenza and SARS-CoV-2 infections by week of onset

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• 6/6 sequenced A(H3N2) 

viruses belonged to 

subclade 2a2 
Vaccine effectiveness (VE) against symptomatic influenza among children 

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No. of 

influenza 

infections*

No. of 

person-days

Incidence per 1,000

person-days

Adjusted VE†

% (95% CI)

Vaccinated 6 7,292 0.82

71 (31 ‒ 90) Not Vaccinated 28 15,678 1.79

Study period: October 23, 2022 – February 10, 2023.

*3 influenza infections were censored because onset occurred within 14 days of vaccination.

† VE was estimated from Cox proportional hazards model with time-varying influenza vaccination status, age, presence of at least one higher-risk condition 

(self-report of asthma, immunocompromised state, serious heart condition, or other chronic lung disease), and receipt of 2 or more COVID-19 vaccine 

doses before the analysis period. 
• Single geographic area (central WI)

 Predominant viruses similar in study population and across US

• Adults aged ≥65 years excluded

 Generally have lower VE estimates against A(H3N2) 

• Small sample sizes 

 Wide confidence intervals

 Unable to estimate VE for A(H1N1)pdm09 or age groups

• Confounding and bias with observational studies

 Comparable estimates across two study designs

Limitations

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• Interim results indicate substantial vaccine-induced protection against 

influenza A during 2022-23 season

‒ VE 54% against medically attended influenza A in children and working aged 

adults 

‒ VE 71% against symptomatic influenza A in children

• All characterized viruses from the study population belonged to the same 

genetic subclade as the viruses included in the 2022–23 Northern Hemisphere 

influenza vaccine

Summary

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Jennifer King 

Carla Rottscheit 

Adam Bissonnette 

Gina Burbey 

Liz Armagost 

Brooklyn Arbs 

Saydee Benz 

Riley Bonifer

Bobbi Bradley 

Michaela Braun 

Brianna Breu 

Corey-Beth Cielinski

Christian Delgadillo 

Leila Deering 

Heather Dirkx 

Roxy Eibergen 

Alex Ermeling

Kelsey Ewert

Kallie Falteisek

Rachel Fernandez 

Hope Florence 

Sandy Freeman 

Wayne Frome

Tammy Gault 

Emily Gruenling

Sherri Guzinski 

Angela Harless 

Mitch Hertel

Garrett Heuer

Lee Jepsen

Julie Karl 

Burney Kieke 

Stephanie Kohl 

Sarah Kohn 

Diane Kohnhorst 

Sarah Kopitzke 

Tamara Kronenwetter Koepel 

Erik Kronholm 

Kate Lassa 

Thao Le

Alaura Lemieux 

Carrie Marcis 

Megan Maronde

Dave McClure 

Isaac McCready 

Andrea McGaver

Karen McGreevey 

Nidhi Mehta 

Laura Michalik 

Vicki Moon

Jennifer Moran 

Mike Owens 

DeeAnn Polacek 

Martha Presson 

Nicole Price 

Maxine Racanelli

Chris Rayburn 

Miriah Rotar 

Jesse Rozmarynowski

Jackie Salzwedel

Juan Saucedo 

Kelly Scheffen 

Alex Slenczka

Jacob Solis 

Elisha Stefanski 

Melissa Strupp

Lyndsay Watkins 

Providers, managers, 

and clinical staff at: 

Marshfield Clinic Lake Hallie 

Center 

Marshfield Clinic Wausau Center 

Marshfield Medical CenterEau Claire

Marshfield Medical CenterMarshfield

Marshfield Medical CenterWeston

Acknowledgements

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Joshua Petrie* Kayla Hanson* Jennifer Meece* Edward Belongia*

Marshfield Clinic Health System

Gregg Sylvester*

Karita Ambrose

Ashesh Gandhi

Mendel Haag

CSL Seqirus

Melissa Rolfes*

Brendan Flannery

Jessie Chung

CDC

Gabriele Neumann*

Yoshihiro Kawaoka*

David Pattinson

University of 

Wisconsin – Madison

*Coauthor