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Marshfield Clinic Research InstituteInterim 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
3
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
5Total no. of
patientsNo. (%)
vaccinated †No. (%)
influenza positiveNo.(%) i nfluenza -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 higher -
risk condition§Yes 154 69 (45) 30 (19) 124 (81)
No 391 117 (30) 86 (22) 305 (78)
Self report of ≥2 COVID -
19vaccine 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, i mmunocompromising
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
6Influenza positiveInfluenza -and
SARS -CoV-2 negativeAdjusted 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 r egression 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 –1 7 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- o r guardian -collection of anterior nasal
swab for influenza and SARS -CoV-2 testing
•Information collected from surveys and extracted from electronic health
r
ecords (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 𝑯𝑯𝑹𝑹𝒓𝒓𝒓𝒓𝒓𝒓𝒓𝒓𝒐𝒐𝒐𝒐𝒊𝒊𝒊𝒊 𝒐𝒐𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒐𝒐𝒓𝒓𝒊𝒊𝒓𝒓𝒊𝒊 𝒐𝒐𝒊𝒊𝒓𝒓𝒂𝒂𝒐𝒐 𝒊𝒊 𝒂𝒂𝒗𝒗𝒓𝒓𝒊𝒊 𝒊𝒊𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒓𝒓𝒗𝒗𝒑𝒑𝒓𝒓 𝒓𝒓𝒑𝒑𝒐𝒐 𝒊𝒊−𝒓𝒓𝒊𝒊 𝒂𝒂𝒓𝒓
𝒓𝒓𝒓𝒓
𝒓𝒓𝒓𝒓𝒐𝒐𝒐𝒐𝒊𝒊𝒊𝒊
𝒐𝒐𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒂𝒂𝒐𝒐
𝒊𝒊
𝒂𝒂𝒊𝒊
𝒊𝒊𝒗𝒗𝒓𝒓𝒊𝒊𝒊𝒊𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒓𝒓𝒗𝒗 𝒑𝒑𝒓𝒓
𝒓𝒓𝒑𝒑𝒐𝒐
𝒊𝒊−𝒓𝒓𝒊𝒊
𝒂𝒂𝒓𝒓∗𝟏𝟏𝟏𝟏𝟏𝟏𝟏
•A
djusted for age, higher -risk condition (self -report), COVID -19 vaccination Analysis: Community cohort study
9At 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 receiptCox proportional hazards model with time- varying vaccination status
*Based on documentation in health record according to ACIP recommendations
Characteristics of community cohort
10Total 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 -19vaccine 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 ofthe 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
12No. of
influenza
infections *No. of
person -daysIncidence per 1,000
person -daysAdjusted VE†
% (95% CI)
Vaccinated 6 7,292 0.8271 (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 o ne higher -risk condition
(self -report of asthma, immunocompromised state, serious heart condition, or other chronic lung disease), and receipt of 2 or mo re COVID -19 vaccine
doses before the analysis period.
•Single geographic area (central WI)
Predominant viruses similar in study population and across US
•Adults aged ≥6 5 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 designsLimitations
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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 vaccineSummary
14
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 LeAlaura 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 SalzwedelJuan 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 Center -
Eau Claire
Marshfield Medical Center -
Marshfield
Marshfield Medical Center -
WestonAcknowledgements
15
Edward Belongia*
Joshua Petrie*
Kayla Hanson*
Jennifer Meece*Marshfield Clinic Health System
Gregg Sylvester*
Karita Ambrose
Ashesh Gandhi
Mendel HaagCSL Seqirus
Melissa Rolfes*
Brendan Flannery
Jessie ChungCDC
Gabriele Neumann*
Yoshihiro Kawaoka *
David PattinsonUniversity of
Wisconsin – Madison
*Coauthor