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Cited by 171Influenza Virus Research StudiesRespiratory viral infections researchPneumonia and Respiratory Infections

Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection

Paddock, Christopher D., Liu, Lindy, Denison, Amy M., Bartlett, Jeanine H., Holman, Robert C., DeLeon-Carnes, Marlene, Emery, Shannon L., Drew, Clifton P. +3 more·2012·The Journal of Infectious Diseases
DOI 10.1093/infdis/jir861
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Abstract

BACKGROUND: Influenza B virus infection causes rates of hospitalization and influenza-associated pneumonia similar to seasonal influenza A virus infection and accounts for a substantial percentage of all influenza-related hospitalizations and deaths among those aged <18 years; however, the pathogenesis of fatal influenza B virus infection is poorly described. METHODS: Tissue samples obtained at autopsy from 45 case patients with fatal influenza B virus infection were evaluated by light microscopy and immunohistochemical assays for influenza B virus, various bacterial pathogens, and complement components C4d and C9, to identify the cellular tropism of influenza B virus, characterize concomitant bacterial pneumonia, and describe the spectrum of cardiopulmonary injury. RESULTS: Viral antigens were localized to ciliated respiratory epithelium and cells of submucosal glands and ducts. Concomitant bacterial pneumonia, caused predominantly by Staphylococcus aureus, was identified in 38% of case patients and occurred with significantly greater frequency in those aged >18 years. Pathologic evidence of myocardial injury was identified in 69% of case patients for whom cardiac tissue samples were available for examination, predominantly in case patients aged <18 years. CONCLUSIONS: Our findings suggest that bacterial pneumonia and cardiac injury contribute to fatal outcomes after infection with influenza B virus and that the frequency of these manifestations may be age related.

AI snapshot

Written from the paper’s full text.

TL;DR

In a 45-patient autopsy series of fatal influenza B virus infection, death was often rapid and was frequently accompanied by bacterial pneumonia or myocardial injury. Cardiac injury and/or bacterial pneumonia were identified in 90% of case patients for whom these features could be assessed.

Key findings

  • Among 45 case patients, median age at death was 11 years (range, 10 months–55 years), and 34 (76%) were aged <18 years; median time from illness onset to death was 3 days (range, 1–22 days), with 24 of 35 (69%) dying within 4 days.
  • Pathologic evidence of concomitant bacterial pneumonia was present in 17 (38%) case patients; among those with bacterial pneumonia, *Staphylococcus aureus* was confirmed in 13 (76%), including 7 with methicillin-resistance markers and 11 with Panton-Valentine leukocidin markers.
  • Myocardial injury was identified in 20 of 29 (69%) case patients with cardiac tissue available; 10 had unequivocal myocarditis, and C4d/C9 IHC staining was seen in 19 of 28 (68%) tested.
  • Cardiac injury and bacterial pneumonia were prominent: one or both features were identified in 90% of case patients for whom these pathologic characteristics could be assessed, and cardiac muscle damage was evident in 85% of evaluated patients without bacterial pneumonia.

Methods

  • Retrospective autopsy case series of tissue samples submitted to the CDC from patients with suspected infectious cause of death during May 2000–February 2010; 45 patients with confirmed influenza B virus infection were examined.
  • Histopathology and immunohistochemistry assessed airway, lung, cardiac, and lymph node tissues; influenza B viral antigens were detected with pooled monoclonal antibodies against nucleocapsid and hemagglutinin, and bacterial coinfection was assessed with tissue Gram/silver stains plus IHC for selected bacterial antigens.
  • Molecular analysis used real-time RT-PCR for influenza B hemagglutinin and lineage-specific probes, plus multiplex real-time PCR for *S. aureus* *nuc*, PVL, and *mecA* genes; categorical features were compared with two-sided Fisher’s exact test and continuous data with Wilcoxon rank-sum test.

Limitations

  • The paper states that the study was limited by restricted analysis of case patients for whom an autopsy was performed and tissue samples were sent to the CDC, and by qualitative and quantitative differences among submitted tissue samples.
  • The text also makes evident that this is a selected autopsy cohort with missing data for some clinical and pathologic features, so frequencies may not represent all fatal influenza B infections.
  • The paper notes uncertainty about pathogenic mechanisms, including that no viral antigens were detected in damaged myocardium and influenza B nucleic acids were amplified from myocardium in only 1 case patient, leaving the relative contributions of viral-mediated injury and ischemia unresolved.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/infdis/jir861

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 57 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Age >18 years was the only feature that differed significantly between case patients with and without evidence of histologically confirmed bacterial pneumonia (P < .001).

    “Age .18years was the only feature that differed significantly between case patients with and without evidence of histologically confirmed bacterial pneumonia (P , .001) (Table 1).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Other pulmonary lesions, including intraalveolar hemorrhage and edema, interstitial pneumonia, and alveolitis, were observed in <=50% of case patients without evidence of bacterial pneumonia.

    “Other pulmonary lesions, including intraalveolar hemorrhage and edema, interstitial pneumonia (Figure 1F), and alveolitis were observed in #50% of case patients without evidence of bacterial pneumonia (Table 2).”
    Quote in the paperNot a substantial claim
  • Findingown data

    All case patients with pneumonia due to S. aureus and 1 due to S. pyogenes showed diffusely necrotizing pulmonary lesions, accompanied by abundant hemorrhage and edema, distinguished by coalesced areas of necrosis and hemorrhage that destroyed the normal architecture of the lungs.

    “All of the case patients with pneumonia due to infection with S. aureus and 1 due to S. pyogenes showed diffusely necrotizing pulmonary lesions, accompanied by abundant hemorrhage and edema, distinguished by coalesced areas of necrosis and hemorrhage that destroyed the normal architecture of the lungs (Figure 1E).”
    Quote in the paperSubstantial claim
  • Findingown data

    Seventeen (38%) case patients had pathologic evidence of a concomitant bacterial pneumonia.

    “Seventeen (38%) case patients had pathologic evidence of a concomitant bacterial pneumonia.”
    Quote in the paperSubstantial claim
  • Findingown data

    Bronchiolitis was observed in 40% of case patients without a superimposed bacterial infection.

    “Bronchiolitis was observed in 40% of case patients without a superimposed bacterial infection (Figure 1C).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 21
  • Classified as probably not a substantial claim. 25

  • May combine two claims.

    Findingown data

    IHC and PCR assays confirmed coinfection with S. aureus in 13 (76%) of the patients with bacterial pneumonia, of whom 7 had genetic markers for methicillin resistance and 11 for Panton-Valentine leukocidin.

    “IHC and PCR assays confirmed coinfection with S. aureus in 13 (76%) of the patients with bacterial pneumonia, of whom 7 had genetic markers for methicillin resistance and 11 for Panton-Valentine leukocidin.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Erythrophagocytosis was identified in lymph nodes adjacent to trachea and bronchi of 10 (34%) of the 29 case patients for whom these tissues were available.

    “Erythrophagocytosis was identified in lymph nodes adjacent to trachea and bronchi of 10 (34%) of the 29 case patients for whom these tissues were available (Figure 1D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The epithelial surfaces of the airways were often denuded and associated with necrosis and hemorrhage; in most cases, the basal layer of epithelium and basement membrane were preserved.

    “The epithelial surfaces of these airways were often denuded and associated with necrosis and hemorrhage; however, in most cases, the basal layer of epithelium and basement membrane were preserved (Figure 1A).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    All other years were represented by 1 influenza B virus lineage or a combination of Yamagata-like and Victoria-like strains.

    “All other years were represented by 1 influenza B virus lineage or a combination of Yamagata-like and Victoria-like strains.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Illnesses occurred during December-April among the 44 case patients for whom this information was recorded.

    “Illnesses occurred during December-April among the 44 case patients for whom this information was recorded.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Only Yamagata-like strains were identified from 2008 (n=11), whereas Victoria-like strains were identified in all tissues from case patients from 2003 (n=4), 2007 (n=9), and 2009 (n=9).

    “Only Yamagata-like strains were identified from 2008 (n 5 11), whereas Victoria-like strains were identified in all tissues from case patients from 2003 (n 5 4), 2007 (n 5 9), and 2009 (n 5 9).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Of case patients for whom antigens could be detected and a duration of illness was available, 13 (72%) died within 4 days after illness onset and only 2 (11%) survived for >7 days, including a 13-year-old child with acute myeloblastic leukemia in whom viral antigens were detected by IHC at 22 days.

    “Of case patients for whom antigens could be detected and a duration of illness was available, 13 (72%) died within 4 days after illness onset and only 2 (11%) survived for .7 days, including a 13-year-old child with acute myeloblastic leukemia in whom viral antigens were detected by IHC at 22 days.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The median age of death for case patients was 11 years (range, 10 months to 55 years), and 34 (76%) were aged <18 years.

    “The median age of death for case patients was 11 years (range, 10 months to 55 years); 34 (76%) case patients were aged ,18 years.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Tissue samples from 45 case patients (29 female and 16 male) with influenza B virus infection were examined.

    “Tissue samples from 45 case patients (29 female and 16 male patients) with influenza B virus infection were examined (Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Place of death was recorded for 42 case patients; 11 (26%) died at home, 3 (7%) died en route to a hospital, 9 (21%) died at a clinic or shortly after arrival at an emergency department, and 19 (45%) died during hospitalization.

    “Place of death was recorded for 42 case patients; of these, 11 (26%) died at home, 3 (7%) died en route to a hospital, 9 (21%) died at a clinic or shortly after arrival at an emergency department, and 19 (45%) died during hospitalization.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Pre-existing medical conditions considered high risk for severe influenza, other than young age, were identified in 13 (43%) of the case patients for whom these data were available.

    “Pre-existing medical conditions considered to be high risk for severe influenza, other than young age, were identified in 13 (43%) of the case patients for whom these data were available.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The median number of days from illness onset until death was 3 (range, 1-22 days) among 35 patients, and 24 (69%) of these case patients died within 4 days after illness onset.

    “The median number of days from illness onset until death was 3 (range, 1-22 days) among the 35 patients for whom this information was available; 24 (69%) of these case patients died within 4 days after illness onset.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of the influenza B viruses that could be characterized, 25 were Victoria-like and 17 Yamagata-like strains.

    “of the influenza B viruses that could be characterized, 25 were Victoria-like and 17 Yamagata-like strains (Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Close inspection of glandular epithelium occasionally revealed focal necrosis.

    “Close inspection of glandular epithelium occasionally revealed focal necrosis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Antigens were also identified in the epithelium of submucosal glands and ciliated ducts of the trachea and bronchi and uncommonly in airspaces, comprising predominantly detached strips of ciliated airway epithelium, or single cells, situated freely within the alveoli.

    “Antigens were also identified in the epithelium of submucosal glands and ciliated ducts of the trachea and bronchi (Figure 2C and 2D) and uncommonly in airspaces, comprising predominantly detached strips of ciliated airway epithelium, or single cells, situated freely within the alveoli.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Viral antigens were detected infrequently in respiratory tissues from most IHC-positive patients, and extensive staining was relatively unusual.

    “Viral antigens were detected infrequently in respiratory tissues from most IHC-positive patients, and extensive staining was relatively unusual.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Histological evidence of myocardial injury was characterized in 1 case patient by a small acute myocardial infarct and, in 6 others, by variably sized foci of shrunken or hypereosinophilic myocytes lacking cross-striations and nuclei.

    “Histological evidence of myocardial injury was characterized in 1 case patient by a small acute myocardial infarct and, in 6 others, by variably sized foci of shrunken or hypereosinophilc myocytes lacking cross-striations and nuclei (Figure 3B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For most case patients in this series, death followed a remarkably rapid clinical progression, regardless of demonstrable bacterial pneumonia: 50% of all case patients died within 3 days after illness onset, and 70% died within 4 days.

    “For most case patients in this series, death followed a remarkably rapid clinical progression, regardless of demonstrable bacterial pneumonia: 50% of all case patients died within 3 days after illness onset, and 70% died within 4 days.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Histological features of myocarditis were apparent in 50% of these patients; the cardiac tissue samples from the other 50% demonstrated multifocal IHC evidence of damage that was histologically compatible with ischemic necrosis in the absence of conspicuous inflammatory cell infiltrates.

    “Histological features of myocarditis were apparent in 50% of these patients; of surprise, the cardiac tissue samples from the other 50% demonstrated multifocal IHC evidence of damage that was histologically compatible with ischemic necrosis in the absence of conspicuous inflammatory cell infiltrates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For 17 case patients, there was histological evidence of myocyte damage, including 10 with unequivocal myocarditis, characterized by multiple discrete foci of myocyte necrosis accompanied by clusters of interstitial lymphocytes, macrophages, and occasional neutrophils.

    “For 17 case patients, there was histological evidence of myocyte damage, including 10 with unequivocal myocarditis, characterized by multiple discrete foci of myocyte necrosis accompanied by clusters of interstitial lymphocytes, macrophages, and occasional neutrophils (Figure 3A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Cardiac injury and bacterial pneumonia were prominent findings in this cohort, and one or both features were identified in 90% of the case patients for whom these pathologic characteristics could be assessed.

    “Indeed, cardiac injury and bacterial pneumonia were prominent findings in this cohort, and one or both features were identified in 90% of the case patients for whom these pathologic characteristics could be assessed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    This pattern of staining was observed in the myocardium of each case patient with abnormal histological findings for whom tissues remained for testing and in cardiac tissues of 3 other case patients lacking specific histological evidence of myocyte injury.

    “This pattern of staining was observed in the myocardium of each case patient with abnormal histological findings for whom tissues remained for testing (Figures 3C-3F) and in cardiac tissues of 3 other case patients lacking specific histological evidence of myocyte injury.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Only two distinct lineages of influenza B viruses, Victoria-like and Yamagata-like, currently circulate among human populations.

    “Only 2 distinct lineages of influenza B viruses, comprising the Victoria-like and Yamagata-like strains, currently circulate among human populations [4]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Rota, 1990, Cocirculation of two distinct evolutionary lineages of influenza type B virus since 1983, Virology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Influenza B viruses seldom predominate during seasonal influenza epidemics, but when they do, mortality statistics are generally intermediate to those attributable to influenza A virus subtypes.

    “Influenza B viruses seldom predominate during seasonal influenza epidemics, but when this occurs, mortality statistics are generally intermediate to those attributable to the influenza A virus subtypes [6][7][8][9].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [6] Nolan, 1980, Morbidity and mortality associated with influenza B in the United States, 1979–1980. A report from the Center for Disease Control, J Infect Dis source

      Not checked in the free run.

    • cites [7] Glezen, 1980, Epidemiologic observations of influenza B virus infections in Houston, Texas, 1976–1977, Am J Epidemiol source

      Not checked in the free run.

    • cites [8] Simmerman, 2009, Incidence, seasonality and mortality associated with influenza pneumonia in Thailand: 2005–2008, PLoS One source

      Not checked in the free run.

    • cites [9] Centers for Disease Control and Prevention, 2010, Estimates of deaths associated with seasonal influenza—United States, 1976–2007, MMWR Morb Mortal Wkly Rep

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Negative controls included cardiac tissues with no histologic evidence of inflammation or myocyte injury, obtained at autopsy from 8 patients who died suddenly of a noninfectious cause and from 15 patients who died of confirmed viral or bacterial infections other than influenza B virus infection.

    “Negative controls included cardiac tissues with no histologic evidence of inflammation or myocyte injury, obtained at autopsy from 8 patients who died suddenly of a noninfectious cause and from 15 patients who died of confirmed viral or bacterial infections other than influenza B virus infection.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Skeletal myopathy is described in 14%-48% of children infected with influenza B virus.

    “Skeletal myopathy is described in 14%-48% of children infected with influenza B virus [26,40,41]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [26] Peltola, 2003, Influenza A and B infections in children, Clin Infect Dis source

      Not checked in the free run.

    • cites [40] Wang, 2009, Clinical and laboratory analysis of influenza B infection in children in Taichung, Taiwan during the 2006–2007 flu season, Pediatr Neonatol source

      Not checked in the free run.

    • cites [41] Chi, 2008, Clinical features of children infected with different strains of influenza B in southern Taiwan, Pediatr Infect Dis J source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    S. aureus has been the most commonly identified etiology among US hospitalized pediatric patients with influenza-associated bacterial pneumonia since the 2003-2004 influenza season.

    “which has been the most commonly identified etiology among US hospitalized pediatric patients with influenza-associated bacterial pneumonia since the 2003-2004 influenza season [16,32].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Finelli, 2008, Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection, Pediatrics source

      Not checked in the free run.

    • cites [32] Dawood, 2010, Influenza-associated pneumonia in children hospitalized with laboratory-confirmed influenza, 2003–2008, Pediatr Infect Dis J source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    34% of the 309 seasonal influenza-associated deaths in children reported to the CDC during 2004-2008 were attributed to influenza B.

    “Of note, 34% of the 309 seasonal influenza-associated deaths in children reported to the CDC during 2004-2008 were attributed to influenza B [16] (CDC, unpublished data)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Finelli, 2008, Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection, Pediatrics source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Of the 115 pediatric influenza-associated deaths in the United States reported to the CDC during the 2010-2011 influenza season, 44 (38%) involved influenza B virus infection.

    “of the 115 pediatric influenza-associated deaths in the United States reported to the CDC during the 2010-2011 influenza season, 44 (38%) involved influenza B virus infection [49]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Centers for Disease Control and Prevention, 2011, Influenza-associated pediatric deaths—United States, September 2010–August 2011, MMWR Morb Mortal Wkly Rep

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Our study was limited by its restricted analysis of case patients for whom an autopsy was performed and tissue samples sent to the CDC and by qualitative and quantitative differences among case patient tissue samples submitted for evaluation.

    “Our study was limited by its restricted analysis of case patients for whom an autopsy was performed and tissue samples sent to the CDC and by qualitative and quantitative differences among case patient tissue samples submitted for evaluation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Influenza B is clinically indistinguishable from seasonal influenza A, causes similar rates of hospitalization and influenza-associated pneumonia, and accounts for a substantial percentage of all influenza-related hospitalizations and deaths in patients aged <18 years.

    “contemporary studies indicate that influenza B is clinically indistinguishable from seasonal influenza A, causes similar rates of hospitalization and influenzaassociated pneumonia, and accounts for a substantial percentage of all influenza-related hospitalizations and deaths in patients aged ,18 years [6,8,[24][25][26][27].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [6] Nolan, 1980, Morbidity and mortality associated with influenza B in the United States, 1979–1980. A report from the Center for Disease Control, J Infect Dis source

      Not checked in the free run.

    • cites [8] Simmerman, 2009, Incidence, seasonality and mortality associated with influenza pneumonia in Thailand: 2005–2008, PLoS One source

      Not checked in the free run.

    • cites [24] Liou, 1987, Children hospitalized with influenza B infection, Pediatr Infect Dis J source

      Not checked in the free run.

    • cites [25] Hite, 2007, Medically attended pediatric influenza during the resurgence of the Victoria lineage of influenza B virus, Int J Infect Dis source

      Not checked in the free run.

    • cites [26] Peltola, 2003, Influenza A and B infections in children, Clin Infect Dis source

      Not checked in the free run.

    • cites [27] Dawood, 2010, Burden of seasonal influenza hospitalization in children, United States, 2003 to 2008, J Pediatr source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A cardiac tissue sample from a patient with Coxsackie B1 viral myocarditis was used as a positive control.

    “A cardiac tissue sample from a patient with Coxsackie B1 viral myocarditis was used as a positive control.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The specificity of the influenza B virus IHC assay was assessed by evaluating its reactivity with formalin-fixed, paraffin-embedded Madin-Darby canine kidney cells infected with influenza B virus strains Beijing/243/97 and HK/16/03 and with influenza A virus subtypes H1N1, H3N2, and H5N1.

    “Its specificity was assessed by evaluating its reactivity with formalin-fixed, paraffin-embedded Madin-Darby canine kidney cells infected with influenza B virus strains Beijing/243/97 and HK/16/03 and with influenza A virus subtypes H1N1, H3N2, and H5N1.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Fatal influenza B virus infection occurs most frequently among pediatric patients, but influenza B is also associated with lethal outcomes and substantial seasonal morbidity among adults.

    “Fatal influenza B virus infection occurs most frequently among pediatric patients; however, influenza B is also associated with lethal outcomes and substantial seasonal morbidity among adults [28,29].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Lee, 2010, Outcomes of adults hospitalized with severe influenza, Thorax source

      Not checked in the free run.

    • cites [29] Aebi, 2010, Co-infection of influenza B and streptococci causing severe pneumonia and septic shock in healthy women, BMC Infect Dis source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Preferential binding of influenza B viruses to receptors represented by sialic acid connected to galactose by an α-2,6 linkage (SAα2,6Gal) has been identified in vitro and is predicted from a structural analysis of the influenza B hemagglutinin molecule.

    “Preferential binding of influenza B viruses to receptors represented by sialic acid connected to galactose by a a-2, 6 linkage (SAa2, 6Gal) has been identified in vitro and is predicted from a structural analysis of the influenza B hemagglutinin molecule [46]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Wang, 2007, Structural basis for receptor specificity of influenza B virus hemagglutinin, Proc Nat Acad Sci U S A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Life-threatening consequences exacted by coinfections with influenza B virus and S. aureus or S. pyogenes are increasingly described.

    “the life-threatening consequences exacted by coinfections with influenza B virus and S. aureus or S. pyogenes are increasingly described [16,29,50]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [16] Finelli, 2008, Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection, Pediatrics source

      Not checked in the free run.

    • cites [29] Aebi, 2010, Co-infection of influenza B and streptococci causing severe pneumonia and septic shock in healthy women, BMC Infect Dis source

      Not checked in the free run.

    • cites [50] Scaber, 2011, Group A streptococcal infections during the seasonal influenza outbreak 2010/11 in South East England, Euro Surveill source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Myocarditis is also reported occasionally among patients with fatal influenza A virus infection.

    “Myocarditis is also reported occasionally among patients with fatal influenza A virus infection [2,10,14]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Taubenberger, 2008, The pathology of influenza virus infections, Annu Rev Pathol source

      Not checked in the free run.

    • cites [10] Martin, 1959, Asian influenza A in Boston, 1957–1958. I. Observations in thirty-two influenza-associated fatal cases, AMA Arch Intern Med source

      Not checked in the free run.

    • cites [14] Guarner, 2006, Histopathologic and immunohistochemical features of fatal influenza A virus infection in children during the 2003–2004 season, Clin Infect Dis source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The few studies to describe in vivo distribution of influenza virus antigens in respiratory tissues from deceased patients have focused specifically on influenza A viruses.

    “The few studies to describe in vivo distribution of influenza virus antigens in respiratory tissues from deceased patients have focused specifically on influenza A viruses [14,15]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Guarner, 2006, Histopathologic and immunohistochemical features of fatal influenza A virus infection in children during the 2003–2004 season, Clin Infect Dis source

      Not checked in the free run.

    • cites [15] Shieh, 2010, 2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States, Am J Pathol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    IHC stains for C4d and C9 have been used to identify early myocardial infarcts in patients who die before an influx of leukocytes can occur.

    “IHC stains for C4d and C9 have been used to identify early myocardial infarcts in patients who die before an influx of leukocytes can occur [18]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Jenkins, 2010, The utility of C4d, C9, and troponin T immunohistochemistry in acute myocardial infarction, Arch Pathol Lab Med source

      Not checked in the free run.

39 of 39

  • The authors state this as an assumption.

    No comprehensive studies describe the pathology of influenza B virus infection in a large series of patients with fatal disease or distinguish the pathology of disease with and without concomitant bacterial pneumonia.

    “To our knowledge, there are no comprehensive studies to describe the pathology of influenza B virus infection in a large series of patients with fatal disease or to distinguish the pathology of disease with and without concomitant bacterial pneumonia.”

  • The paper relies on this without support.

    No large studies have specifically identified cardiac injury as a frequent manifestation of fatal influenza B.

    “however, we are not aware of any large studies that specifically identify cardiac injury as a frequent manifestation of fatal influenza B.”

  • The paper relies on this without support.

    The pathogenic mechanisms that lead to injury to striated fibers in the heart and skeletal muscles are unknown.

    “The pathogenic mechanisms that lead to injury to striated fibers in the heart and skeletal muscles remain unknown.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In seasonal epidemics, influenza bacterial coinfection is associated with increases in hospital admissions, more severe symptoms, and increases in mortality.

    “In seasonal epidemics, influenza bacterial coinfection is associated with increases in hospital admissions,4, 5 more severe symptoms,6 and increases in mortality.7”

    From The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. (2016) · cites this paper as [7]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Influenza B confirmation percentage does not match cohort size

    Minor

    The paper reports 45 case patients, so 36 patients represent 80%, not 82%. A denominator of 44 would give approximately 82%, but no different denominator is specified for this statement.

    Reported 82 · recomputed 80

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Emery, 2009, Multiplex BHQplus™ hydrolysis probe rRT-PCR assay for discrimination of current Yamagata-like and Victoria-like influenza B viruses [abstract M13]

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Authors
Paddock, C. D., Liu, L., Denison, A. M., Bartlett, J. H., Holman, R. C., DeLeon-Carnes, M., Emery, S. L., Drew, C. P., Shieh, W.-J., Uyeki, T. M., & Zaki, S. R.
Affiliations
Centers for Disease Control and Prevention (US)
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2012-01-30
Volume
205
Issue
6
Pages
895-905
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1093/infdis/jir861
OpenAlex
W2162655125
Semantic Scholar
18926c6c817df030b3a6b9a0e7687f3773df1a15
Cited by
171
References
50
Citations by year
2026: 6 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 23 · 2019: 24 · 2018: 12 · 2017: 15 · 2016: 19 · 2015: 10 · 2014: 9 · 2013: 10 · 2012: 9
FWCI
9.07
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
Keywords
influenza B, fatal influenza, myocardial injury, bacterial pneumonia, Staphylococcus aureus, influenza-associated pneumonia, cell tropism, complement C4d, complement C9, age-related mortality, autopsy findings
MeSH terms
Adolescent, Adult, Antigens, Viral, Autopsy, Child, Child, Preschool, Female, Heart Injuries, Hospitalization, Humans, Infant, Infant, Newborn, Influenza, Human, Male, Middle Aged, Myocardium, Influenza B virus, Specimen Handling, Staphylococcus aureus, Cohort Studies, Pneumonia, Bacterial, Young Adult, Viral Tropism

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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