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Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children
Samantha M Olson1, Margaret M Newhams2, Natasha B Halasa3
1Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Insights
Influenza vaccination reduced severe illness in children during a season with drifted viruses. The vaccine provided significant protection against life-threatening pediatric influenza, even with mismatched strains.
Area of Science:
- Pediatric critical care medicine
- Virology
- Vaccinology
Background:
- The 2019-2020 influenza season featured predominantly 2 antigenically drifted influenza viruses.
- This provided a unique opportunity to evaluate influenza vaccine effectiveness (VE) against severe pediatric disease caused by mismatched strains in the US.
Purpose of the Study:
- To assess the VE of the influenza vaccine against life-threatening pediatric influenza during a season with predominantly vaccine-mismatched viruses.
- To analyze VE stratified by age, virus type, and disease severity.
Main Methods:
- A test-negative design was employed, enrolling children under 18 admitted to the ICU with acute respiratory infection.
- Respiratory specimens were analyzed using reverse-transcription polymerase chain reaction (RT-PCR) and sequencing.
- Vaccine effectiveness was estimated by comparing vaccination odds in influenza-positive cases versus influenza-negative controls.
Main Results:
- 159 critically ill influenza cases and 132 controls were enrolled. 52% of sequenced A/H1N1pdm09 viruses and most B-lineage viruses were vaccine-mismatched.
- Overall VE against critical influenza was 63% (95% CI, 38% to 78%).
- VE was 75% against life-threatening influenza and 78% against matched A(H1N1)pdm09 viruses, but only 47% against mismatched A(H1N1)pdm09 viruses.
Conclusions:
- Influenza vaccination was associated with a reduced risk of critical and life-threatening influenza illness in children.
- Even with predominant viral drift, the influenza vaccine demonstrated significant protective effects against severe outcomes in pediatric patients.
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.
