. 2023 Feb 8;76(3):e280-e290.

doi: 10.1093/cid/ciac477.

Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children

Natasha B Halasa¹, Andrew J Spieker², Cameron C Young³, Samantha M Olson⁴, Margaret M Newhams³, Justin Z Amarin¹, Kristin L Moffitt^{5

6}, Mari M Nakamura^{5

6

7}, Emily R Levy⁸, Vijaya L Soma⁹, Rana Talj¹, Scott L Weiss¹⁰, Julie C Fitzgerald¹⁰, Elizabeth H Mack¹¹, Aline B Maddux¹², Jennifer E Schuster¹³, Bria M Coates¹⁴, Mark W Hall¹⁵, Stephanie P Schwartz¹⁶, Adam J Schwarz¹⁷, Michele Kong¹⁸, Philip C Spinella¹⁹, Laura L Loftis²⁰, Gwenn E McLaughlin²¹, Charlotte V Hobbs²², Courtney M Rowan²³, Melania M Bembea²⁴, Ryan A Nofziger²⁵, Christopher J Babbitt²⁶, Cindy Bowens²⁷, Heidi R Flori²⁸, Shira J Gertz²⁹, Matt S Zinter³⁰, John S Giuliano³¹, Janet R Hume³², Natalie Z Cvijanovich³³, Aalok R Singh³⁴, Hillary A Crandall³⁵, Neal J Thomas³⁶, Melissa L Cullimore³⁷, Manish M Patel⁴, Adrienne G Randolph^{3

6

38}; Pediatric Intensive Care Influenza; Overcoming COVID-19 Investigators

Collaborators, Affiliations

Collaborators

Michele Kong, Mary Glas Gaspers, Katri V Typpo, Ronald C Sanders, Irby Katherine, Mourani Peter, Adam J Schwarz, Christopher J Babbitt, Harvey Helen, Natalie Z Cvijanovich, Matt S Zinter, Aline B Maddux, Christina M Osborne, Shankman Sara, Peter M Mourani, Port Emily, Kevin A Van, Christopher L Carroll, John S Giuliano, Gwenn E McLaughlin, Keiko M Tarquinio, Kelly N Michelson, Bria M Coates, Courtney M Rowan, Kari Wellnitz, Guru Bhoojhawon, Janice E Sullivan, Vicki L Montgomery, Kevin M Havlin, Tamara T Bradford, Becky J Riggs, Melania M Bembea, Adrienne G Randolph, Margaret M Newhams, Sabrina R Chen, Cameron C Young, Kristin L Moffitt, Mari M Nakamura, Ryan W Carroll, Phoebe H Yager, Neil D Fernandes, Heidi R Flori, Sabrina M Heidemann, Janet R Hume, Emily R Levy, Charlotte V Hobbs, Lora Martin, Lacy Malloch, Kengo Inagaki, Anita Dhanrajani, Jennifer E Schuster, Abigail Kietzman, Shannon Hill, Philip C Spinella, Melissa L Cullimore, Russell J McCulloh, Katharine N Clouser, Shira J Gertz, Lawrence C Kleinman, Simon Li, Steven M Horwitz, Adam J Ratner, Heda Dapul, Vijaya L Soma, Michael A Keenaghan, Aalok R Singh, Ilana Harwayne-Gidansky, Saul R Hymes, Sule Doymaz, Stephanie P Schwartz, Tracie C Walker, Mark W Hall, Steven L Shein, Amanda N Lansell, Ryan A Nofziger, Mary A Staat, Julie C Fitzgerald, Scott Weiss, Neal J Thomas, Ericka L Fink, Joseph A Carcillo, Elizabeth H Mack, Laura S Smallcomb, Natasha B Halasa, Laura Stewart, Yesenia Romero, Haya Hayek, Laura L Loftis, Alvaro Coronado Munoz, Cindy Bowens, Mia Maamari, Hillary Crandall, Lincoln S Smith, John K McGuire

Affiliations

¹ Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
⁴ COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁵ Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.
⁶ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Antimicrobial Stewardship Program, Boston Children's Hospital, Boston, Massachusetts, USA.
⁸ Divisions of Pediatric Infectious Diseases and Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁹ Department of Pediatrics, Division of Infectious Diseases, New York University Grossman School of Medicine and Hassenfeld Children's Hospital, New York, New York, USA.
¹⁰ Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹¹ Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
¹² Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
¹³ Division of Pediatric Infectious Disease, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA.
¹⁴ Division of Pediatric Critical Care Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁵ Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
¹⁶ Department of Pediatrics, Division of Critical Care, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁷ Division of Critical Care Medicine, Children's Hospital Orange County (CHOC), Orange, California, USA.
¹⁸ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁹ Division of Critical Care, Department of Pediatrics, Washington University School of Medicine in St Louis, St. Louis, Missouri, USA.
²⁰ Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA.
²¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA.
²² Department of Pediatrics, Department of Microbiology, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi, USA.
²³ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, Indiana, USA.
²⁴ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁵ Division of Critical Care Medicine, Akron Children's Hospital, Akron, Ohio, USA.
²⁶ Miller Children's and Women's Hospital of Long Beach, Long Beach, California, USA.
²⁷ Department of Pediatrics, Division of Critical Care Medicine, University of Texas Southwestern, Children's Medical Center, Dallas, Texas, USA.
²⁸ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Mott Children's Hospital and University of Michigan, Ann Arbor, Michigan, USA.
²⁹ Division of Pediatric Critical Care, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, New Jersey, USA.
³⁰ Department of Pediatrics, Division of Critical Care, University of California-San Francisco, San Francisco, California, USA.
³¹ Department of Pediatrics, Division of Critical Care, Yale University School of Medicine, New Haven, Connecticut, USA.
³² Division of Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA.
³³ Division of Critical Care Medicine, University of California-San Francisco Benioff Children's Hospital Oakland, Oakland, California, USA.
³⁴ Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla, New York, USA.
³⁵ Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
³⁶ Department of Pediatrics, Penn State Hershey Children's Hospital, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
³⁷ Division of Pediatric Critical Care, Department of Pediatrics, Children's Hospital and Medical Center, Omaha, Nebraska, USA.
³⁸ Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 35717646
PMCID: PMC9384330
DOI: 10.1093/cid/ciac477

Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children

Natasha B Halasa et al. Clin Infect Dis. 2023.

. 2023 Feb 8;76(3):e280-e290.

doi: 10.1093/cid/ciac477.

Authors

Collaborators

Michele Kong, Mary Glas Gaspers, Katri V Typpo, Ronald C Sanders, Irby Katherine, Mourani Peter, Adam J Schwarz, Christopher J Babbitt, Harvey Helen, Natalie Z Cvijanovich, Matt S Zinter, Aline B Maddux, Christina M Osborne, Shankman Sara, Peter M Mourani, Port Emily, Kevin A Van, Christopher L Carroll, John S Giuliano, Gwenn E McLaughlin, Keiko M Tarquinio, Kelly N Michelson, Bria M Coates, Courtney M Rowan, Kari Wellnitz, Guru Bhoojhawon, Janice E Sullivan, Vicki L Montgomery, Kevin M Havlin, Tamara T Bradford, Becky J Riggs, Melania M Bembea, Adrienne G Randolph, Margaret M Newhams, Sabrina R Chen, Cameron C Young, Kristin L Moffitt, Mari M Nakamura, Ryan W Carroll, Phoebe H Yager, Neil D Fernandes, Heidi R Flori, Sabrina M Heidemann, Janet R Hume, Emily R Levy, Charlotte V Hobbs, Lora Martin, Lacy Malloch, Kengo Inagaki, Anita Dhanrajani, Jennifer E Schuster, Abigail Kietzman, Shannon Hill, Philip C Spinella, Melissa L Cullimore, Russell J McCulloh, Katharine N Clouser, Shira J Gertz, Lawrence C Kleinman, Simon Li, Steven M Horwitz, Adam J Ratner, Heda Dapul, Vijaya L Soma, Michael A Keenaghan, Aalok R Singh, Ilana Harwayne-Gidansky, Saul R Hymes, Sule Doymaz, Stephanie P Schwartz, Tracie C Walker, Mark W Hall, Steven L Shein, Amanda N Lansell, Ryan A Nofziger, Mary A Staat, Julie C Fitzgerald, Scott Weiss, Neal J Thomas, Ericka L Fink, Joseph A Carcillo, Elizabeth H Mack, Laura S Smallcomb, Natasha B Halasa, Laura Stewart, Yesenia Romero, Haya Hayek, Laura L Loftis, Alvaro Coronado Munoz, Cindy Bowens, Mia Maamari, Hillary Crandall, Lincoln S Smith, John K McGuire

Affiliations

¹ Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
⁴ COVID-19 Response, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁵ Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.
⁶ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Antimicrobial Stewardship Program, Boston Children's Hospital, Boston, Massachusetts, USA.
⁸ Divisions of Pediatric Infectious Diseases and Pediatric Critical Care Medicine, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁹ Department of Pediatrics, Division of Infectious Diseases, New York University Grossman School of Medicine and Hassenfeld Children's Hospital, New York, New York, USA.
¹⁰ Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
¹¹ Division of Pediatric Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
¹² Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
¹³ Division of Pediatric Infectious Disease, Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA.
¹⁴ Division of Pediatric Critical Care Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁵ Division of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
¹⁶ Department of Pediatrics, Division of Critical Care, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
¹⁷ Division of Critical Care Medicine, Children's Hospital Orange County (CHOC), Orange, California, USA.
¹⁸ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁹ Division of Critical Care, Department of Pediatrics, Washington University School of Medicine in St Louis, St. Louis, Missouri, USA.
²⁰ Section of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA.
²¹ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida, USA.
²² Department of Pediatrics, Department of Microbiology, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi, USA.
²³ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, Indiana, USA.
²⁴ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁵ Division of Critical Care Medicine, Akron Children's Hospital, Akron, Ohio, USA.
²⁶ Miller Children's and Women's Hospital of Long Beach, Long Beach, California, USA.
²⁷ Department of Pediatrics, Division of Critical Care Medicine, University of Texas Southwestern, Children's Medical Center, Dallas, Texas, USA.
²⁸ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Mott Children's Hospital and University of Michigan, Ann Arbor, Michigan, USA.
²⁹ Division of Pediatric Critical Care, Department of Pediatrics, Cooperman Barnabas Medical Center, Livingston, New Jersey, USA.
³⁰ Department of Pediatrics, Division of Critical Care, University of California-San Francisco, San Francisco, California, USA.
³¹ Department of Pediatrics, Division of Critical Care, Yale University School of Medicine, New Haven, Connecticut, USA.
³² Division of Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA.
³³ Division of Critical Care Medicine, University of California-San Francisco Benioff Children's Hospital Oakland, Oakland, California, USA.
³⁴ Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla, New York, USA.
³⁵ Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
³⁶ Department of Pediatrics, Penn State Hershey Children's Hospital, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
³⁷ Division of Pediatric Critical Care, Department of Pediatrics, Children's Hospital and Medical Center, Omaha, Nebraska, USA.
³⁸ Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 35717646
PMCID: PMC9384330
DOI: 10.1093/cid/ciac477

Abstract

Background: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients.

Methods: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity.

Results: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78-2.15; P = .32).

Conclusions: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

Keywords: COVID-19; SARS-CoV-2; children; influenza; intensive care units.

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Conflict of interest statement

Potential conflicts of interest. N. B. H. reports grants or contracts from Sanofi and Quidell outside of the submitted work and an educational grant for honorarium from Genentech. M. M. B. reports grants or contracts from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke, Grifols Investigator Sponsored Research Grant, and NIH/ Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) outside of the submitted work and paid to institution. B. M. C. reports grants or contracts from the NIH, American Thoracic Society, and American Lung Association outside the submitted work and paid to institution and payment to author for expert testimony from Triplett Woolf Garretson, LLC. N. Z. C. reports grants or contracts from the NIH outside of the submitted work. H. R. F. reports grants or contracts from the NIH, National Heart, Lung, and Blood Institute (NHLBI), and NICHD outside of the submitted work; support for attending meetings and/or travel from the Society of Critical Care Medicine; participation on a data and safety monitoring board (DSMB) for a cardiothoracic surgery trial (single center) and a DSMB for an intrathecal chemotherapy trial; an unpaid position on the Michigan Thoracic Society Executive Committed and Pediatric Acute Lung Injury and Sepsis Investigators network Executive Committee; and the following other financial or nonfinancial interests: Lucira Health advisory committee and Aerogen Pharma advisory unfunded. M. W. H. reports grants or contracts from the NIH and royalties from Kiadis outside of the submitted work; participation on a DSMB or advisory board for AbbVie and La Jolla Pharmaceuticals (payment to author); and leadership or fiduciary role on the American Board of Pediatrics (payment to author). J. R. H. reports grants or contracts from the NIH–NICHD outside of the submitted work and participation on a DSMB for an institutional study at the University of Minnesota (no financial reimbursements). M. K. reports grants or contracts from the NIH outside of the submitted work to institution. E. R. L. reports grants or contracts from the NIH outside of the submitted work and paid to institution. M. M. Nakamura reports grants or contracts from Gilead for participation in their remdesivir trial. R. A. N. reports grants or contracts from the NIH outside of the submitted work. C. M. R. reports grants or contracts from the NIH outside of the submitted work and payment for honoraria to author for the Contemporary Critical Care Complications of SCT/Cellular Therapies Conference by MD Anderson. J. E. S. reports grants or contracts from Merck outside of the submitted work and paid to institution. M. S. Z. reports grants or contracts from the NIH outside of the submitted work and paid to institution. A. G. R. reports grants or contracts from the National Institute of Allergy and Infectious Diseases to institution outside of the submitted work; royalties or licenses from UpToDate as a Pediatric Critical Care Section Editor paid to author; and is an unpaid treasurer for International Sepsis Forum. M. L. C. reports grants or contracts to institution for projects unrelated to this work from the CDC. J.C.F. reports an NIH award unrelated to this study and paid to institution. C. V. H. reports payment or honoraria as a consultant for Biofire (bioMérieux). G. E. M. reports payment for expert testimony in a malpractice case involving influenza related death. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

**Figure 1.**
Age distribution of critically ill children with influenza (n = 179) compared with those with COVID-19 (n = 381). Abbreviation: COVID-19, coronavirus disease 2019.

**Figure 2.**
Symptoms at presentation of critically ill children with influenza (n = 179) compared with those with COVID-19 (n = 381). Abbreviation: COVID-19, coronavirus disease 2019.

**Figure 3.**
Comparison of multiorgan involvement in children with severe influenza *(A)* and children with coronavirus disease 2019 *(B)*.

**Figure 4.**
Median length of hospital stay *(A)* and ICU stay *(B)* by age group of critically ill children with influenza (n = 179) compared with those with COVID-19 (n = 381). Abbreviations: COVID-19, coronavirus disease 2019; ICU, intensive care unit.

See this image and copyright information in PMC

References

1. Feldstein LR, Tenforde MW, Friedman KG, et al. Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. JAMA 2021; 325:1074–87. - PMC - PubMed
1. Centers for Disease Control and Prevention . Provisional COVID-19 deaths by sex and age. Available at: https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-by-Sex-and-Age/9bh.... Accessed 27 April 2022.
1. Halasa NB. Update on the pandemic influenza A H1N1 in children. Curr Opin Pediatr 2009; 2010:83–7. - PubMed
1. Bhat N, Wright JG, Broder KR, et al. Influenza-associated deaths among children in the United States 2003–2004. N Engl J Med 2005; 353:2559–67. - PubMed
1. Olson SM, Newhams MM, Halasa NB, et al. Vaccine effectiveness against life-threatening influenza illness in US children. Clin Infect Dis 2022; ciab931. doi:10.1093/cid/ciab931. - DOI - PubMed

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Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children

Collaborators

Affiliations

Life-Threatening Complications of Influenza vs Coronavirus Disease 2019 (COVID-19) in US Children

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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