Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness

Shannon B Leland; Laura D Zambrano; Steven J Staffa; Elizabeth R McNamara; Margaret M Newhams; Natasha Halasa; Justin Z Amarin; Laura S Stewart; Steven L Shein; Christopher L Carroll; Julie C Fitzgerald; Marian G Michaels; Katherine Bline; Melissa L Cullimore; Laura Loftis; Vicki L Montgomery; Asumthia S Jeyapalan; Pia S Pannaraj; Adam J Schwarz; Natalie Z Cvijanovich; Matt S Zinter; Aline B Maddux; Melania M Bembea; Katherine Irby; Danielle M Zerr; Joseph D Kuebler; Christopher J Babbitt; Mary G Gaspers; Ryan A Nofziger; Michele Kong; Bria M Coates; Jennifer E Schuster; Shira J Gertz; Elizabeth H Mack; Benjamin R White; Helen Harvey; Charlotte V Hobbs; Heda Dapul; Andrew D Butler; Tamara T Bradford; Courtney M Rowan; Kari Wellnitz; Mary Allen Staat; Cassyanne L Aguiar; Saul R Hymes; Angela P Campbell; Adrienne G Randolph; RSV-PIC Investigators

doi:10.1093/infdis/jiaf018

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness

J Infect Dis. 2025 Jan 15:jiaf018. doi: 10.1093/infdis/jiaf018. Online ahead of print.

Authors

Shannon B Leland^{1

2}, Laura D Zambrano³, Steven J Staffa¹, Elizabeth R McNamara¹, Margaret M Newhams¹, Natasha Halasa⁴, Justin Z Amarin⁴, Laura S Stewart⁴, Steven L Shein⁵, Christopher L Carroll⁶, Julie C Fitzgerald⁷, Marian G Michaels⁸, Katherine Bline⁹, Melissa L Cullimore¹⁰, Laura Loftis¹¹, Vicki L Montgomery¹², Asumthia S Jeyapalan¹³, Pia S Pannaraj¹⁴, Adam J Schwarz¹⁵, Natalie Z Cvijanovich¹⁶, Matt S Zinter¹⁷, Aline B Maddux¹⁸, Melania M Bembea¹⁹, Katherine Irby²⁰, Danielle M Zerr²¹, Joseph D Kuebler²², Christopher J Babbitt²³, Mary G Gaspers²⁴, Ryan A Nofziger²⁵, Michele Kong²⁶, Bria M Coates²⁷, Jennifer E Schuster²⁸, Shira J Gertz²⁹, Elizabeth H Mack³⁰, Benjamin R White³¹, Helen Harvey³², Charlotte V Hobbs³³, Heda Dapul³⁴, Andrew D Butler³⁵, Tamara T Bradford³⁶, Courtney M Rowan³⁷, Kari Wellnitz³⁸, Mary Allen Staat³⁹, Cassyanne L Aguiar⁴⁰, Saul R Hymes⁴¹, Angela P Campbell³, Adrienne G Randolph^{1

2

42}; RSV-PIC Investigators

Collaborators

RSV-PIC Investigators:
Merry Tomcany, Kelly N Michelson, Heather E Price, Ronald C Sanders, Lexie Dixon, Katri V Typpo, Ilana Harwayne-Gidansky, Suden Kucukak, Sabrina R Chen, Eve Listerud, Ofelia Vargas-Shiraishi, Betty Oberle, Frances Zorensky, Rachel Mansour, Jaycee Jumarang, Marla Johnston, Jenny L Bush, Shawn Dickey, Shannon Hill, Melissa Sullivan, Abigail Kietzman, Candice Colston, Meghan Murdock, Heather Kelley, Laura Wright-Sexton, Maygan Martin, Lora Martin, Lacy Malloch, Kayla Patterson, Cameron Sanders, Chelsea Rohlfs, Marilyn Rice, Miranda Howard, Makayla Murphy, Vijaya L Soma, Adam J Ratner, Megan J Job, Colleen Mennie, Kamala Simkhada, Kristina A Betters, Haya Hayek, Molly Maranto, Aubrie Waters, Maggie Flowers, Kevin Havlin, Jamie Furlong-Dillard, Melissa Porter, Jennifer Nason, Madison Ray, Kristen Gossett, Hillary Crandall, Evan Heller, Jennifer Foley, Rajashri Rasal, Christine Marlow, Anurithi Senthil, Kimberly Myers, Betsy Tudor, Amanda Adler, Nereyda Garcia, Natalie Treister, Patrick S McQuillen, Kathleen Sun, Denise Villarreal-Chico, Sophia Kainaroi, John V Williams

Affiliations

¹ Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
² Departments of Anaesthesia and Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
³ Coronavirus and Other Respiratory Viruses Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁴ Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁵ Division of Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
⁶ Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut, USA.
⁷ Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
⁸ Division of Infectious Diseases, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁹ Division of Pediatric Critical Care Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
¹⁰ Division of Pediatric Critical Care, Department of Pediatrics, Children's Nebraska, Omaha, Nebraska, USA.
¹¹ Department of Pediatrics, Baylor College of Medicine, Division of Pediatric Critical Care, Texas Children's Hospital, Houston, Texas, USA.
¹² Department of Pediatrics, University of Louisville and Norton Children's Hospital, Louisville, Kentucky, USA.
¹³ Division of Pediatric Critical Care Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
¹⁴ Division of Infectious Diseases, Departments of Pediatrics, University of California San Diego, and Rady Children's Hospital. San Diego, California, USA.
¹⁵ Division of Critical Care Medicine, Children's Hospital Orange County, Orange, California, USA.
¹⁶ Division of Critical Care, Department of Pediatrics, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
¹⁷ Division of Critical Care, Department of Pediatrics, UCSF Benioff Children's Hospital San Francisco, California, USA.
¹⁸ Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
¹⁹ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁰ Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
²¹ Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, Washington, USA.
²² Division of Pediatric Critical Care, Department of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, New York, USA.
²³ Division of Pediatric Critical Care, Miller Children's and Women's Hospital of Long Beach, Long Beach, California, USA.
²⁴ Division of Critical Care, Department of Pediatrics, Banner Children's at Diamond Children's Medical Center, Tucson, Arizona, USA.
²⁵ Division of Critical Care Medicine, Akron Children's Hospital, Akron, Ohio, USA.
²⁶ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
²⁷ Division of Pediatric Critical Care Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
²⁸ Division of Pediatric Infectious Diseases, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA.
²⁹ Division of Pediatric Critical Care, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, New Jersey, USA.
³⁰ Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
³¹ Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
³² Division of Pediatric Critical Care, Department of Pediatrics, University of California - San Diego, Rady Children's Hospital, San Diego, California, USA.
³³ Division of Infectious Diseases, Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
³⁴ Division of Pediatric Critical Care Medicine, Department of Pediatrics, New York University Grossman School of Medicine, New York, New York, USA.
³⁵ Division of Pediatric Critical Care, St. Christopher's Hospital for Children, Philadelphia, Pennsylvania, USA.
³⁶ Division of Cardiology, Department of Pediatrics, Louisiana State University Health Sciences Center and Children's Hospital of New Orleans, New Orleans, Louisiana, USA.
³⁷ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, Indiana, USA.
³⁸ Division of Pediatric Critical Care, Stead Family Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
³⁹ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
⁴⁰ Division of Pediatric Rheumatology, Children's Hospital of The King's Daughters, Eastern Virginia Medical School, Norfolk, Virginia, USA.
⁴¹ Division of Pediatric Infectious Diseases, Department of Pediatrics, Bernard and Millie Duker Children's Hospital, Albany Med Health System, Albany, New York, USA.
⁴² Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 39812486
DOI: 10.1093/infdis/jiaf018

Abstract

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.

Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.S. PICUs from October through December 2022. We assigned CPS-Ped (0=discharged home at respiratory baseline to 8=death) at admission, days 2-7,10, and 14. We identified predictors of clinical improvement (CPS-Ped≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS).

Results: Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV). Of the 49 (8.4%) infants whose CPS-Ped score worsened by 2 points after admission, one died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age <3 months, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2,031 for hospital LOS.

Conclusions: CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV.

Keywords: acute hypoxic respiratory failure; acute respiratory distress syndrome; intensive care unit; outcome; pediatric.

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