Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children
Authors: Olson Samantha M , Newhams Margaret M , Halasa Natasha B , Feldstein Leora R , Novak Tanya , Weiss Scott L , Coates Bria M , Schuster Jennifer E , Schwarz Adam J , Maddux Aline B , Hall Mark W , Nofziger Ryan A , Flori Heidi R , Gertz Shira J , Kong Michele , Sanders Ronald C , Irby Katherine , Hume Janet R , Cullimore Melissa L , Shein Steven L , Thomas Neal J , Stewart Laura S , Barnes John R , Patel Manish M , Randolph Adrienne G ,   Pediatric Intensive Care Influenza Investigators, Michele Kong , Murdock Meghan , Sanders Ronald C , Irby Katherine , Hefley Glenda , Schwarz Adam J , Flores Cathy , Vargas-Shiraishi Ofelia , Maddux Aline B , Mourani Peter M , Van Kevin A , Coates Bria M , Shukla Avani , Chavez Jairo , Randolph Adrienne G , Newhams Margaret M , Novak Tanya , Chen Sabrina R , Jung Emily , Flori Heidi R , Dahmer Mary K , Jayachandran Chaandini , Hume Janet R , Goertzen Lexie , Faanes Brittany , Schuster Jennifer E , Bledsoe Megan C , Clark Shannon E , Cullimore Melissa L , Wellman Rachel L , Gertz Shira J , Nofziger Ryan A , Twinem Nicole , Shein Steven L , Lansell Amanda N , Rasal Rajashri , Hall Mark W , Flowers Maggie , Steele Lisa , Weiss Scott L , Bush Jenny L , Burnett Ryan H , Thomas Neal J , Spear Debra , Halasa Natasha B , Stewart Laura S , Lynch Tricia L , Olson Samantha M , Patel Manish M , Feldstein Leora R , Barnes John R , Le Shoshona , DaSilva Juliana , Keong Lisa , Stark Thomas , Kondor Rebecca Garten , Michael Wu 
Published: December 2021

Abstract

Background
Predominance of 2 antigenically drifted influenza viruses during the 2019–2020 season offered an opportunity to assess vaccine effectiveness against life-threatening pediatric influenza disease from vaccine-mismatched viruses in the United States.

Methods
We enrolled children aged &lt;18 years admitted to the intensive care unit with acute respiratory infection across 17 hospitals. Respiratory specimens were tested using reverse-transcription polymerase chain reaction for influenza viruses and sequenced. Using a test-negative design, we estimated vaccine effectiveness comparing odds of vaccination in test-positive case patients vs test-negative controls, stratifying by age, virus type, and severity. Life-threating influenza included death or invasive mechanical ventilation, vasopressors, cardiopulmonary resuscitation, dialysis, or extracorporeal membrane oxygenation.

Results
We enrolled 159 critically ill influenza case-patients (70% ≤8 years; 51% A/H1N1pdm09 and 25% B-Victoria viruses) and 132 controls (69% were aged ≤8 years). Among 56 sequenced A/H1N1pdm09 viruses, 29 (52%) were vaccine-mismatched (A/H1N1pdm09/5A+156K) and 23 (41%) were vaccine-matched (A/H1N1pdm09/5A+187A,189E). Among sequenced B-lineage viruses, majority (30 of 31) were vaccine-mismatched. Effectiveness against critical influenza was 63% (95% confidence interval [CI], 38% to 78%) and similar by age. Effectiveness was 75% (95% CI, 49% to 88%) against life-threatening influenza vs 57% (95% CI, 24% to 76%) against non-life-threating influenza. Effectiveness was 78% (95% CI, 41% to 92%) against matched A(H1N1)pdm09 viruses, 47% (95% CI, –21% to 77%) against mismatched A(H1N1)pdm09 viruses, and 75% (95% CI, 37% to 90%) against mismatched B-Victoria viruses.

Conclusions
During a season when vaccine-mismatched influenza viruses predominated, vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children.