Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza — United States, 2021–22 Influenza Season
Weekly / December 16, 2022 / 71(50);1589–1596
Katherine Adams, MPH1,*; Katie J. Tastad, MPH1,*; Stacy Huang, MPH1,2; Dawud Ujamaa, MS1,3; Krista Kniss, MPH1; Charisse Cummings, MPH1; Arthur Reingold, MD4; Jeremy Roland, MPH4; Elizabeth Austin, MPH5; Breanna Kawasaki, MPH5; James Meek, MPH6; Kimberly Yousey-Hindes, MPH6; Evan J. Anderson, MD7,8,9; Kyle P. Openo, DrPH8,9,10; Libby Reeg, MPH11; Lauren Leegwater, MPH11; Melissa McMahon, MPH12; Erica Bye, MPH12; Mayvilynne Poblete, MPH13; Zachary Landis, MPH13; Nancy L. Spina, MPH14; Kerianne Engesser, MPH14; Nancy M. Bennett, MD15; Maria A. Gaitan15; Eli Shiltz, MPH16; Nancy Moran, DVM16; Melissa Sutton, MD17; Nasreen Abdullah, MD17; William Schaffner, MD18; H. Keipp Talbot, MD18; Kristen Olsen19; Holly Staten19; Christopher A. Taylor, PhD20; Fiona P. Havers, MD20; Carrie Reed, DSc1; Alicia Budd, MPH1; Shikha Garg, MD1; Alissa O’Halloran, MSPH1,†; Lynnette Brammer, MPH1,† (View author affiliations)View suggested citation
What is already known about this topic?
Influenza and SARS-CoV-2 viruses individually contribute to pediatric morbidity. The prevalence and severity of coinfection with influenza and SARS-CoV-2 are less well understood.
What is added by this report?
During the 2021–22 influenza season, 6% of hospitalized pediatric influenza patients had SARS-CoV-2 coinfection; a higher percentage of patients with coinfection required invasive or noninvasive respiratory support compared with those with influenza only. Among influenza-associated pediatric deaths, 16% had SARS-CoV-2 coinfection; only one coinfected decedent received influenza antivirals, and none had been fully vaccinated against influenza.
What are the implications for public health practice?
The public should adopt prevention strategies, including influenza and COVID-19 vaccination, and consider mask use during high respiratory virus circulation.
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The 2022–23 influenza season shows an early rise in pediatric influenza-associated hospitalizations (1). SARS-CoV-2 viruses also continue to circulate (2). The current influenza season is the first with substantial co-circulation of influenza viruses and SARS-CoV-2 (3). Although both seasonal influenza viruses and SARS-CoV-2 can contribute to substantial pediatric morbidity (3–5), whether coinfection increases disease severity compared with that associated with infection with one virus alone is unknown. This report describes characteristics and prevalence of laboratory-confirmed influenza virus and SARS-CoV-2 coinfections among patients aged <18 years who had been hospitalized or died with influenza as reported to three CDC surveillance platforms during the 2021–22 influenza season. Data from two Respiratory Virus Hospitalizations Surveillance Network (RESP-NET) platforms (October 1, 2021–April 30, 2022),§ and notifiable pediatric deaths associated¶ with influenza virus and SARS-CoV-2 coinfection (October 3, 2021–October 1, 2022)** were analyzed. SARS-CoV-2 coinfections occurred in 6% (32 of 575) of pediatric influenza-associated hospitalizations and in 16% (seven of 44) of pediatric influenza-associated deaths. Compared with patients without coinfection, a higher proportion of those hospitalized with coinfection received invasive mechanical ventilation (4% versus 13%; p = 0.03) and bilevel positive airway pressure or continuous positive airway pressure (BiPAP/CPAP) (6% versus 16%; p = 0.05). Among seven coinfected patients who died, none had completed influenza vaccination, and only one received influenza antivirals.†† To help prevent severe outcomes, clinicians should follow recommended respiratory virus testing algorithms to guide treatment decisions and consider early antiviral treatment initiation for pediatric patients with suspected or confirmed influenza, including those with SARS-CoV-2 coinfection who are hospitalized or at increased risk for severe illness. The public and parents should adopt prevention strategies including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and staying up-to-date with recommended influenza and COVID-19 vaccinations for persons aged ≥6 months.
CDC collects data on influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network (FluSurv-NET), a population-based RESP-NET system that includes more than 250 acute care hospitals.§§ Since March 2020, CDC has also collected data on COVID-19–associated hospitalizations through another RESP-NET platform, the COVID-19–associated Hospitalization Surveillance Network (COVID-NET). Influenza and SARS-CoV-2 testing¶¶ is driven by clinician decisions or hospital testing policies, with laboratory, clinical, and notifiable disease database sources used to identify patients.*** A FluSurv-NET patient was defined as a person who 1) was a resident of the surveillance catchment area, 2) had a hospital admission during October 1, 2021–April 30, 2022, and 3) had a positive influenza test result within 14 days before or anytime during hospitalization. Coinfected patients were those who met the FluSurv-NET definition and who also 1) had laboratory-confirmed influenza and SARS-CoV-2 infections during the same hospitalization, or 2) were identified through COVID-NET and had a COVID-19–associated hospital admission occurring within 14 days before or after an influenza-associated hospitalization. A patient was considered to have received the current seasonal influenza vaccine if ≥1 dose was administered ≥14 days before the positive influenza test result.†††
Data on influenza-associated pediatric deaths that occurred during October 3, 2021–October 1, 2022, were obtained from the Influenza-Associated Pediatric Mortality Surveillance System. A notifiable death is defined as a death in a person aged <18 years resulting from a clinically compatible illness confirmed to be influenza by laboratory testing§§§ without a period of complete recovery between illness onset and death. State and local health departments report investigations of these deaths to CDC using a standardized case report form, which includes data on demographic characteristics, influenza testing, bacterial and viral co-detections, clinical diagnoses and complications, medication use, and influenza vaccination. Coinfections with SARS-CoV-2 were identified using the “viral coinfection” field, with either COVID-19 or SARS-CoV-2 indicated in free text.
Across all data sources, patients were eligible to be included in this analysis if they were aged <18 years and had evidence of influenza virus infection. Information on COVID-19 vaccination and antiviral treatment was not included because of lack of systematic ascertainment for patients across data sources. Demographic and clinical characteristics, in-hospital interventions, and outcomes are reported by illness status (influenza and SARS-CoV-2 coinfection and influenza infection alone) as frequencies and proportions, with between-group comparisons analyzed using Pearson’s chi-square tests for hospitalizations and Fisher’s exact tests for deaths. Medians and IQRs are presented for continuous variables, with between-group comparisons analyzed using a Wilcoxon rank sum test. Data were analyzed using SAS software (version 9.4, SAS Institute). These activities were reviewed by CDC and were consistent with applicable federal law and CDC policy.¶¶¶
Hospitalizations. During October 1, 2021–April 30, 2022, FluSurv-NET identified 575 pediatric influenza-associated hospitalizations, including 32 (6%) patients who were coinfected with SARS-CoV-2 and 543 (94%) who had influenza alone (hereafter, influenza) (Figure). Underlying medical conditions were reported for the majority of hospitalized patients with coinfection (56%) and with influenza (58%) (p = 0.81), whereas receipt of seasonal influenza vaccination was less prevalent among those with coinfections (17%) than among those with influenza (42%) (p = 0.02) (Table 1). A higher proportion of patients with coinfection than with influenza received invasive mechanical ventilation (13% versus 4%; p = 0.03) and BiPAP or CPAP (16% versus 6%; p = 0.05). No significant differences were found between patients with coinfection and with influenza in the prevalence of intensive care unit (ICU) admission (p = 0.20). No in-hospital deaths were identified with FluSurv-NET in either group.
Deaths. Forty-four influenza-associated pediatric deaths were reported to the Influenza-Associated Pediatric Mortality Surveillance System during the 2021–22 influenza season, including seven (16%) decedents who had SARS-CoV-2 coinfection (Figure). Among influenza vaccine–eligible children who died and for whom data were available, zero of six with coinfections and five (16%) of 31 with influenza had been vaccinated against influenza (p = 0.57) (Table 2). The most common complications among decedents with coinfections were pneumonia, acute respiratory distress syndrome, and bronchiolitis. Among decedents with influenza, the most common complications were pneumonia, seizures, and acute respiratory distress syndrome. Cardiomyopathy or myocarditis occurred in five (16%) of 32 decedents with influenza and none with coinfection (p = 0.57). One or more underlying medical conditions were reported for four of five children with coinfections who died and 21 (58%) of 36 with influenza (p = 0.63). Influenza antiviral therapy was administered to one child with a coinfection who died and 17 (46%) decedents with influenza (p = 0.21).
The 2020–21 influenza season, which occurred during the COVID-19 pandemic, was characterized by historically low influenza circulation (6). However, an unusually late increase in influenza activity occurred in April 2022 during the 2021–22 season (7). In this analysis of 2021–22 influenza data from three CDC surveillance systems, among all pediatric patients who received testing for both influenza and SARS-CoV-2 viruses and who were hospitalized or died with influenza, most had underlying medical conditions and were not fully vaccinated against seasonal influenza. Influenza and SARS-CoV-2 coinfections were infrequent (representing 6% of hospitalizations and 16% of deaths within these populations), likely in part because of lower-than-usual influenza virus circulation. However, these data identified increased use of invasive and noninvasive mechanical ventilation among coinfected patients, indicating potentially more severe disease among children and adolescents with influenza and SARS-CoV-2 coinfection. These findings also highlight the underuse of influenza antivirals and seasonal influenza vaccines, particularly among persons aged <18 years with influenza virus and SARS-CoV-2 coinfections who died.
These findings represent a small number of cases of influenza and SARS-CoV-2 coinfection, thereby limiting the ability to draw firm conclusions. The high degree of cocirculation of multiple respiratory viruses during the current season (1,2), and the higher-than-usual early-season influenza activity, underscore the importance of increasing awareness among parents and providers that influenza and SARS-CoV-2 coinfections occur in pediatric patients and that coinfection can potentially cause more severe illness. For pediatric patients with acute respiratory illness symptoms with suspected severe illness, testing for both influenza and SARS-CoV-2, and other respiratory viruses is critical to facilitate early detection of coinfections and help guide clinical treatment and management (8).
The findings in this report are subject to at least six limitations. First, viral testing was performed at the clinician’s discretion or according to hospital policy and might have been influenced by factors including clinical presentation, severity of illness, and previous testing. Both influenza-only and SARS-CoV-2 coinfection cases were not detected if testing for influenza virus and SARS-CoV-2 was not performed for patients with acute respiratory illness. However, coinfected patients might be overrepresented in these results among patients with more severe disease (e.g., on respiratory support) if they were more likely to have been tested for both influenza virus and SARS-CoV-2. Second, information on COVID-19 vaccination and SARS-CoV-2 antiviral treatment was not included because this information could not be systematically ascertained for patients across all data sources. Third, whereas the Influenza-Associated Pediatric Mortality Surveillance System reflects data across all U.S. states and territories, FluSurv-NET and COVID-NET catchment areas include approximately 9%–10% of the U.S. population, limiting the generalizability of results. Fourth, circulation of influenza A and B viruses was lower during 2021–22 than during pre–COVID-19 seasons, thus reducing the number of patients included in the analysis and limiting the ability to examine the clinical effects of COVID-19 on the clinical course of influenza. Ongoing surveillance can help to assess the clinical progression and associated severity of pediatric influenza and SARS-CoV-2 coinfections. Fifth, because of the variability in testing practices found in passive surveillance systems such as the Influenza-Associated Pediatric Mortality Surveillance System (e.g., influenza testing not being performed or being performed late in the course of the illness when influenza could not be detected), pediatric deaths were likely underreported. Finally, SARS-CoV-2–only infections were not reported because these data were not available in the Influenza-Associated Pediatric Mortality Surveillance System.
To prevent and mitigate the incidence of severe respiratory virus–associated illness during periods of influenza virus and SARS-CoV-2 cocirculation, the public and parents should be aware of the risk for pediatric coinfection and adopt prevention strategies, including considering wearing well-fitted, high-quality masks when respiratory virus circulation is high and annual influenza vaccination and up-to-date COVID-19 vaccination (9,10). To identify coinfections with influenza virus and SARS-CoV-2, clinicians should follow recommended testing algorithms for patients with acute respiratory illness symptoms in outpatient, emergency department, and hospital settings. Clinical guidance on early initiation of antiviral treatment for influenza and SARS-CoV-2 should be followed for pediatric patients with suspected or confirmed influenza or SARS-CoV-2 infections (or both), who are hospitalized, have severe or progressive disease, or are at increased risk for complications (9,10).
Ashley Coates, Pam Daily Kirley, Brenna Hall, Joelle Nadle, Monica Napoles, Sherry Quach, Gretchen Rothrock, Tiffany Tsukuda, California Emerging Infections Program; Shua J. Chai, California Emerging Infections Program, CDC; Nisha B. Alden, Sharon Emmerling, Diane Garcia, Madelyn Lensing, Jordan Surgnier, Millen Tsegaye, Isaac Armistead, Colorado Department of Public Health and Environment; Maria Correa, Daewi Kim, Carol Lyons, Julie Plano, Connecticut Emerging Infections Program, Yale School of Public Health; Gracie Chambers, Taylor Eisenstein, Emily Fawcett, Annabel Patterson, Foundation for Atlanta Veterans Education and Research, Georgia Emerging Infections Program, Georgia Department of Public Health; Atlanta Veterans Affairs Medical Center; Marina Bruck, Rayna Ceaser, Sabrina Hendrick, Johanna Hernandez, Asmith Joseph, Grayson Kallas, Stephanie Lehman, Jana Manning, Allison Roebling, Suzanne Segler, Chandler Surell, Katelyn Ward, Hope Wilson, Emory University School of Medicine; Maya L. Monroe, Patricia Ryan, Maryland Department of Health; Chloe Brown, Jim Collins, Justin Henderson, Shannon Johnson, Sue Kim, Alexander Kohrman, Sanchitha Meda, Alyanna Melicor, Val Tellez Nunez, Michigan Department of Health and Human Services; Kayla Bilski, Natalie Bullis, Kathy Como-Sabetti, Grace Hernandez, Jackie Johnson, Tenzin Kunkyi, Ruth Lynfield, Erica Mumm, Kieu My Phi, Sif Nave, Elizabeth Snyderman, Nicholas Zerzan, Minnesota Department of Health; Cory Cline, Sri HarshaChinta, Melissa Judson, Sunshine Martinez, Mark Montoya, Florent Nkouaga, Susan Ropp, Jasmyn Sanchez, Yomei P. Shaw, Chad Smelser, Daniel M. Sosin, New Mexico Department of Health; Kathy M. Angeles, Molly Bleecker, Adrienne Domen, Nancy Eisenberg, Emily Hancock, Sarah A. Khanlian, Sarah Lathrop, Wickliffe Omondi, Francesca Pacheco, Dominic Rudin, Yadira Salazar-Sanchez, New Mexico Emerging Infections Program; Jennifer Akpo, Celina Chavez, Murtada Khalifa, Kelly Plymesser, Alesia Reed, Yassir Talha, CDC Foundation, New Mexico Department of Health; Suzanne McGuire, Adam Rowe, Jemma Rowlands, New York State Department of Health; Sophrena Bushey, Christina Felsen, Christine Long, Kevin Popham, University of Rochester School of Medicine and Dentistry; Laurie Billing, Julie Freshwater, Denise Ingabire-Smith, Ann Salvator, Rebekah Sutter, Ohio Department of Health; Sam Hawkins, M. Andraya Hendrick, Public Health Division, Oregon Health Authority; Bentley Akoko, Kathy Billings, Katie Dyer, Anise Elie, Gail Hughett, Karen Leib, Tiffanie Markus, Terri McMinn, Danielle Ndi, Manideepthi Pemmaraju, Vanderbilt University Medical Center; Ashton Bruno, Amanda Carter, Ryan Chatelain, Melanie Crossland, Andrea George, Rosie Gonzalez, Mary Hill, Andrew Haraghey, Andrea Price, Emily Roberts, Courtney Sacco, Ashley Swain, Salt Lake County Health Department; Janelle Delgadillo, Utah Department of Health and Human Services.
Corresponding author: Katherine Adams, firstname.lastname@example.org, 404-639-0630.
1Influenza Division, National Center for Immunization and Respiratory Diseases, CDC; 2Goldbelt Professional Services, Herndon, Virginia; 3General Dynamics Information Technology, Atlanta, Georgia; 4University of California, Berkeley, California Emerging Infections Program, Oakland, California; 5Colorado Department of Public Health and Environment; 6Connecticut Emerging Infections Program, Yale School of Public Health, New Haven, Connecticut; 7Departments of Pediatrics and Medicine, Emory University School of Medicine, Atlanta, Georgia; 8Georgia Emerging Infections Program, Georgia Department of Public Health, Atlanta, Georgia; 9Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; 10Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia; 11Michigan Department of Health and Human Services; 12Minnesota Department of Health; 13New Mexico Emerging Infections Program, University of New Mexico, Albuquerque, New Mexico; 14New York State Department of Health; 15University of Rochester School of Medicine and Dentistry, Rochester, New York; 16Ohio Department of Health; 17Oregon Health Authority; 18Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee; 19Salt Lake County Health Department, Salt Lake City, Utah; 20Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Stacy Huang reports personal fees from Goldbelt Professional Services. Dawud Ujamaa reports personal fees from General Dynamics Information Technology. Evan J. Anderson reports grants from Pfizer, Merck, PaxVax, Micron, Sanofi-Pasteur, Janssen, MedImmune, and GSK outside the submitted work; personal fees from Sanofi-Pasteur, Pfizer, Medscape, Kentucky Bioprocessing, Inc, Janssen, GSK, WCG and ACI Clinical, and Moderna outside the submitted work; and his institution has also received funding from the National Institutes of Health to conduct clinical trials of COVID-19 vaccines. Libby Reeg reports grants from Michigan Department of Health and Human Services. Lauren Leegwater reports grants from the Michigan Department of Health and Human Services. Eli Shiltz reports grants from the Council of State and Territorial Epidemiologists (CSTE) outside the submitted work. Nancy Moran reports grants from CSTE, outside the submitted work. No other potential conflicts of interest were disclosed.
* These authors contributed equally to this report.
† These senior authors contributed equally to this report.
§ Data from FluSurv-NET beyond April 30, 2022, did not include variables required to determine influenza and SARS-CoV-2 coinfection status.
** The 2021–22 influenza season was defined as MMWR week 40 of 2021 through MMWR week 39 of 2022 (October 3, 2021–October 1, 2022). https://ndc.services.cdc.gov/wp-content/uploads/MMWR_Week_overview.pdf
†† Receipt of COVID-19 treatment was not collected on patients in this report.
§§ FluSurv-NET data from the 2021–22 influenza season included county data from 13 U.S. states: California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota, New Mexico, New York, Ohio, Oregon, Tennessee, and Utah. Data from Iowa were excluded from FluSurv-NET during this season because of lack of capture of all required variables. COVID-NET data included all contributing FluSurv-NET counties as well as statewide surveillance data from Maryland.
¶¶ Influenza testing for FluSurv-NET includes rapid antigen, molecular assay, rapid molecular assay, immunofluorescence assay, viral culture, or serology. COVID-19 testing includes rapid antigen, molecular assay, or serology.
*** Trained staff members reviewed laboratory records, medical charts, and reportable conditions databases to identify eligible patients. Data on demographics, clinical characteristics, in-hospital interventions, and clinical outcomes were abstracted using standardized case report forms.
††† Ascertainment of vaccination status was performed using hospital records, state immunization registries, primary care provider surveys, and patient or proxy interview.
§§§ Influenza testing for influenza-associated pediatric mortality includes commercial rapid diagnostic tests, viral culture, fluorescent antibody, enzyme immunoassay, reverse transcription–polymerase chain reaction, and immunohistochemistry.
¶¶¶ 45 C.F.R. part 46.102(l)(2); 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
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FIGURE. Number of children and adolescents aged <18 years who were hospitalized* or died† with influenza alone and influenza and SARS-CoV-2 coinfections, by month — United States, 2021–22 influenza season
* Influenza Hospitalization Surveillance Network; data beyond April 30, 2022, did not include variables required to determine influenza and SARS-CoV-2 coinfection status.
† Influenza-Associated Pediatric Mortality Surveillance System.
Suggested citation for this article: Adams K, Tastad KJ, Huang S, et al. Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza — United States, 2021–22 Influenza Season. MMWR Morb Mortal Wkly Rep 2022;71:1589–1596. DOI: http://dx.doi.org/10.15585/mmwr.mm7150a4.
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