Vaccine Effectiveness Against Life-Threatening Influenza Illness in US Children

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

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)230-238
Number of pages9
JournalClinical Infectious Diseases
Issue number2
StatePublished - Jul 15 2022

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases


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