Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children

• Published in: Clinical infectious diseases Vol. 75; no. 2; pp. 230 - 238
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 25-08-2022
• Subjects: influenza; severity; case control; pediatrics; vaccination
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciab931

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 <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.
In the largest study of its kind, vaccination averted most critical (63%) and life-threatening (75%) influenza among children aged <18 years. This reduction was impressive because vaccine components were mismatched to the 2 predominant circulating influenza strains during this season.