Saturday, December 17, 2022

MMWR: Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Pediatric Patients Who Died - U.S. , 2021–22 Flu season



#17,178

Because the spread of influenza was greatly suppressed during the first two years to the COVID pandemic, there is only limited data on the impact of coinfection with influenza (A or B) and the various incarnations of SARS-CoV-2.  

Some early studies, however - based primarily on pre-Omicron COVID variants - have suggested that coinfection could lead to worse outcomes

In 2020 - in PHE Study: Co-Infection With COVID-19 & Seasonal Influenza - we looked at a Public Health England study that warned that being co-infected with influenza and COVID more than doubled the risk of death over having COVID alone.

Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design

Authors: J STOWE, PhD 1* , E TESSIER, MsC 1* , H ZHAO, PhD 1 , R GUY, BSc 2 , B MULLER-PEBODY, PhD 2 , M ZAMBON, PhD 3 , N ANDREWS, PhD 4 , M RAMSAY, MBBS, 1 , J LOPEZ BERNAL, PhD 1

While being infected with Influenza lowered the risk of contracting SARS-CoV-2 (likely due to `viral interference'), among those who did contract both, they determined:

 `. . . the risk of death was nearly six times greater among individuals with a SARS-CoV-2 and influenza coinfection than those with neither influenza nor SARS-CoV-2 and that this effect is significantly higher than the risk associated with SARS-CoV-2 infection alone.'

While the lack of a 2020-2021 influenza season severely hampered data collection, in November of 2021 - in PLoS NTD: Clinical & Virological Impact of Single and Dual Infections with influenza A (H1N1) and SARS-CoV-2 - we saw another study out of China (based on limited 2020 data) that found:

  • Co-infection had an increased odds of acute kidney injury, acute heart failure, secondary bacterial infections, multilobar infiltrates and admittance to ICU than monoinfection.
  • Co-infection by SARS-CoV-2 and H1N1 caused more severe disease than monoinfection by either virus in adult inpatients. 

A more recent study (see March 2022 The Lancet: SARS-CoV-2 Co-infection With Influenza Viruses, RSV, or Adenoviruses) suggested that influenza-COVID co-infections could be relatively common, and could significantly increase winter mortality.

Using mostly pre-Omicron data, they reported:

Co-infection with influenza viruses was associated with increased odds of receiving invasive mechanical ventilation compared with SARS-CoV-2 monoinfection (table). SARS-CoV-2 co-infections with influenza viruses and adenoviruses were each significantly associated with increased odds of death.

Drilling down into the data, coinfection with influenza (among hospitalized patients) was linked to a 4-fold increased likelihood of requiring mechanical ventilation, and a roughly doubled risk for death.

How much all of this applies to our current (or future) COVID environment is difficult to say.  SARS-CoV-2 is a continually evolving target, and coinfection with different flu subtypes may produce better or worse outcomes. 

But we do have a new study - published yesterday in the CDC's MMWR - which finds (based on limited data) that children and adolescents hospitalized with a COVID-Influenza coinfection during the 2021-2022 flu season tended to have worse outcomes than those with influenza alone. 

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


Summary

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.
          (SNIP)

Discussion

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).

          (Continue . . . )

 

Although pediatric flu deaths have been a `reportable' disease by the CDC since 2004, it is estimated that only between 1/3rd and 1/4th of all pediatric flu deaths are captured by surveillance (see 2018's see 2018's Why Flu Fatality Numbers Are So Hard To Determine). 

In the aftermath of the H1N1 pandemic of 2009, the CDC estimated that the likely number of pediatric deaths in the United States ranged from 910 to 1880, or anywhere from 3 to 6 times higher than reported.

With adults - particularly older adults - influenza deaths are even harder to quantify. Many `flu-related' deaths are chalked up to heart attacks, strokes, or `pneumonia'.  All reasons why the death tolls from COVID, and the previous pandemics of 2009, 1968, 1957, and 2018 remain hotly debated. 

While the evidence may not be as robust as we'd like, and future risks and outcomes may change with the arrival of new COVID variants - between these studies, and what we know about repeated infections and `long COVID' - it still makes sense to avoid infection (and coinfection) whenever possible.