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Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection
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.
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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.
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54 Own result · 24 Not checked yet · 4 Own method · 3 Own interpretation
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“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
plaincorrelationaln = 45 ·- Asserted: passes — The authors put it forward as true.
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“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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“Seventeen (38%) case patients had pathologic evidence of a concomitant bacterial pneumonia.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
plainn = 45- Asserted: passes — The authors put it forward as true.
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“Bronchiolitis was observed in 40% of case patients without a superimposed bacterial infection (Figure 1C).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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“Viral antigens were detected by IHC staining of respiratory tissues from 28 case patients.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Laboratory Confirmation of Influenza B Virus Infection
plainn = 28- Asserted: passes — The authors put it forward as true.
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In the paper
“For 17 (38%) case patients, intraalveolar collections of neutrophils and macrophages containing intracellular bacteria were identified by using tissue Gram or silver techniques (Table 1).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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In the paper
“Antigens of influenza B virus were detected predominantly in the nuclei of ciliated columnar epithelium of the trachea and proximal bronchi and less frequently in cells lining the bronchioles (Table 2; Figure 2A and 2B).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Distribution of Viral Antigens
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In the paper
“Tissue samples from case-patients without bacterial pneumonia were more likely to be IHC positive for viral antigens than those from case patients with evidence of bacterial coinfection (P , .001) (Table 1).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Laboratory Confirmation of Influenza B Virus Infection
plaincorrelationaln = 28 ·- Asserted: passes — The authors put it forward as true.
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“Inflammatory cell infiltrates were characterized predominantly by lymphocytes, plasma cells, and macrophages that infiltrated the lamina propria and often extended into the submucosa to involve seromucinous glands and ciliated ducts (Figure 1B).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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“All other years were represented by 1 influenza B virus lineage or a combination of Yamagata-like and Victoria-like strains.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Laboratory Confirmation of Influenza B Virus Infection
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In the paper
“Illnesses occurred during December-April among the 44 case patients for whom this information was recorded.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
plainn = 44- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Laboratory Confirmation of Influenza B Virus Infection
plainn = 11- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Distribution of Viral Antigens
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
plainn = 45- Asserted: passes — The authors put it forward as true.
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In the paper
“Tissue samples from 45 case patients (29 female and 16 male patients) with influenza B virus infection were examined (Table 1).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
plainn = 45- Asserted: passes — The authors put it forward as true.
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“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Patient Characteristics
plainn = 35- Asserted: passes — The authors put it forward as true.
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In the paper
“of the influenza B viruses that could be characterized, 25 were Victoria-like and 17 Yamagata-like strains (Table 1).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Laboratory Confirmation of Influenza B Virus Infection
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In the paper
“Close inspection of glandular epithelium occasionally revealed focal necrosis.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Pulmonary Pathology
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Distribution of Viral Antigens
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In the paper
“Viral antigens were detected infrequently in respiratory tissues from most IHC-positive patients, and extensive staining was relatively unusual.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Distribution of Viral Antigens
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In the paper
“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Cardiac Pathology
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > DISCUSSION
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
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In the paper
“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).”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Cardiac Pathology
plainn = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > DISCUSSION
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Cardiac Pathology
plainn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“Only 2 distinct lineages of influenza B viruses, comprising the Victoria-like and Yamagata-like strains, currently circulate among human populations [4]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Abstract
What the sources say
- Not checked yetcites [4] Rota, 1990, Cocirculation of two distinct evolutionary lineages of influenza type B virus since 1983, Virology source
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In the paper
“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].”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Abstract
What the sources say
- Not checked yetcites [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 yetcites [7] Glezen, 1980, Epidemiologic observations of influenza B virus infections in Houston, Texas, 1976–1977, Am J Epidemiol source
- Not checked yetcites [8] Simmerman, 2009, Incidence, seasonality and mortality associated with influenza pneumonia in Thailand: 2005–2008, PLoS One source
- Not checked yetcites [9] Centers for Disease Control and Prevention, 2010, Estimates of deaths associated with seasonal influenza—United States, 1976–2007, MMWR Morb Mortal Wkly Rep
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In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Histopathology and Immunohistochemistry
plainn = 15- Asserted: passes — The authors put it forward as true.
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In the paper
“Skeletal myopathy is described in 14%-48% of children infected with influenza B virus [26,40,41]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [26] Peltola, 2003, Influenza A and B infections in children, Clin Infect Dis source
- Not checked yetcites [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 yetcites [41] Chi, 2008, Clinical features of children infected with different strains of influenza B in southern Taiwan, Pediatr Infect Dis J source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [16] Finelli, 2008, Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection, Pediatrics source
- Not checked yetcites [32] Dawood, 2010, Influenza-associated pneumonia in children hospitalized with laboratory-confirmed influenza, 2003–2008, Pediatr Infect Dis J source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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)”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > DISCUSSION
What the sources say
- Not checked yetcites [16] Finelli, 2008, Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection, Pediatrics source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [49] Centers for Disease Control and Prevention, 2011, Influenza-associated pediatric deaths—United States, September 2010–August 2011, MMWR Morb Mortal Wkly Rep
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > DISCUSSION
What the sources say
- Not checked yetcites [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 yetcites [8] Simmerman, 2009, Incidence, seasonality and mortality associated with influenza pneumonia in Thailand: 2005–2008, PLoS One source
- Not checked yetcites [24] Liou, 1987, Children hospitalized with influenza B infection, Pediatr Infect Dis J source
- Not checked yetcites [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 yetcites [26] Peltola, 2003, Influenza A and B infections in children, Clin Infect Dis source
- Not checked yetcites [27] Dawood, 2010, Burden of seasonal influenza hospitalization in children, United States, 2003 to 2008, J Pediatr source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A cardiac tissue sample from a patient with Coxsackie B1 viral myocarditis was used as a positive control.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Histopathology and Immunohistochemistry
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Histopathology and Immunohistochemistry
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > DISCUSSION
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“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]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [46] Wang, 2007, Structural basis for receptor specificity of influenza B virus hemagglutinin, Proc Nat Acad Sci U S A source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the life-threatening consequences exacted by coinfections with influenza B virus and S. aureus or S. pyogenes are increasingly described [16,29,50]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [16] Finelli, 2008, Influenza-associated pediatric mortality in the United States: increase of Staphylococcus aureus coinfection, Pediatrics source
- Not checked yetcites [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 yetcites [50] Scaber, 2011, Group A streptococcal infections during the seasonal influenza outbreak 2010/11 in South East England, Euro Surveill source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Myocarditis is also reported occasionally among patients with fatal influenza A virus infection [2,10,14]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [2] Taubenberger, 2008, The pathology of influenza virus infections, Annu Rev Pathol source
- Not checked yetcites [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 yetcites [14] Guarner, 2006, Histopathologic and immunohistochemical features of fatal influenza A virus infection in children during the 2003–2004 season, Clin Infect Dis source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [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 yetcites [15] Shieh, 2010, 2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States, Am J Pathol source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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]”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > 30, 31] (Table
What the sources say
- Not checked yetcites [18] Jenkins, 2010, The utility of C4d, C9, and troponin T immunohistochemistry in acute myocardial infarction, Arch Pathol Lab Med source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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.”
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 the citing paper
“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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“Infection with influenza B virus was identified in 36 (82%) of the case patients by at least 1 assay before submission to the CDC.”
§ Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection > Laboratory Confirmation of Influenza B Virus Infection
Reported 82 · recomputed 80
Citations
Cites
Methicillin-Resistant S. aureus Infections among Patients in the Emergency Department
Moran, G. J., Krishnadasan, A., Gorwitz, R. J., Fosheim, G. E., McDougal, L. K., Carey, R. B., & Talan, D. A. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055356 · Cited by 2,285
Morens, D. M., Taubenberger, J. K., & Fauci, A. S. (2008) · The Journal of Infectious Diseases · doi:10.1086/591708 · Cited by 1,625 · cited 2×
“Pandemic A (H1N1) 1918–1919 10 (NR) 93 Streptococcus pneumoniae [3]”
BackgroundThe Pathology of Influenza Virus Infections
Taubenberger, J. K., & Morens, D. M. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.154316 · Cited by 1,111
Mucus clearance as a primary innate defense mechanism for mammalian airways
Knowles, M. R., & Boucher, R. C. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215217 · Cited by 1,054
Estimates of deaths associated with seasonal influenza --- United States, 1976-2007.
Thompson, M. G., Shay, D. K., Zhou, H., Bridges, C. B., Cheng, P. Y., Burns, E. M., Bresee, J., & Cox, N. J. (2010) · PubMed · Cited by 760
Influenza-Associated Deaths among Children in the United States, 2003–2004
Bhat, N., Wright, J. G., Broder, K. R., Murray, E. L., Greenberg, M. E., Glover, M. J., Likos, A. M., Posey, D. L., Klimov, A., Lindstrom, S. E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051721 · Cited by 648
Self-citationCocirculation of two distinct evolutionary lineages of influenza type B virus since 1983
Rota, P. A., Wallis, T. R., Harmon, M. W., Rota, J. S., Kendal, A. P., & Nerome, K. (1990) · Virology · doi:10.1016/0042-6822(90)90186-u · Cited by 539
2009 Pandemic Influenza A (H1N1)
Shieh, W.-J., Blau, D. M., Denison, A. M., DeLeon-Carnes, M., Adem, P., Bhatnagar, J., Sumner, J., Liu, L., Patel, M., Batten, B., et al. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100115 · Cited by 429
Self-citationOsterhaus, A. D. M. E., Rimmelzwaan, G. F., Martina, B. E. E., Bestebroer, T. M., & Fouchier, R. A. M. (2000) · Science · doi:10.1126/science.288.5468.1051 · Cited by 415
Finelli, L., Fiore, A., Dhara, R., Brammer, L., Shay, D. K., Kamimoto, L., Fry, A., Hageman, J., Gorwitz, R., Bresee, J., et al. (2008) · PEDIATRICS · doi:10.1542/peds.2008-1336 · Cited by 312
Self-citation
Research works printed but not linked: 1
- Emery, 2009, Multiplex BHQplus™ hydrolysis probe rRT-PCR assay for discrimination of current Yamagata-like and Victoria-like influenza B viruses [abstract M13]
Cited by
Sorted by citations
Metlay, J. P., Waterer, G. W., Long, A. C., Anzueto, A., Brozek, J., Crothers, K., Cooley, L. A., Dean, N. C., Fine, M. J., Flanders, S. A., et al. (2019) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201908-1581st · Cited by 3,657
The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis.
Klein, E. Y., Monteforte, B., Gupta, A., Jiang, W., May, L., Hsieh, Y., & Dugas, A. (2016) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12398 · Cited by 574
Rapkiewicz, A., Mai, X., Carsons, S. E., Pittaluga, S., Kleiner, D. E., Berger, J. S., Thomas, S., Adler, N., Charytan, D. M., Gasmi, B., et al. (2020) · EClinicalMedicine · doi:10.1016/j.eclinm.2020.100434 · Cited by 535
“No evidence of complementmediated myocardial damage was present in our cohort, though we and others have demonstrated this previously in the setting of influenza [29,30].”
Influenza virus-related critical illness: pathophysiology and epidemiology
Kalil, A. C., & Thomas, P. G. (2019) · Critical Care · doi:10.1186/s13054-019-2539-x · Cited by 524
The hidden burden of influenza: A review of the extra‐pulmonary complications of influenza infection
Sellers, S. A., Hagan, R. S., Hayden, F. G., & Fischer, W. A. (2017) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12470 · Cited by 455
Influenza-Associated Pediatric Deaths in the United States, 2010–2016
Shang, M., Blanton, L., Brammer, L., Olsen, S. J., & Fry, A. M. (2018) · PEDIATRICS · doi:10.1542/peds.2017-2918 · Cited by 278
Critical care management of adults with community-acquired severe respiratory viral infection
Arabi, Y. M., Fowler, R., & Hayden, F. G. (2020) · Intensive Care Medicine · doi:10.1007/s00134-020-05943-5 · Cited by 263
Influenza Vaccine in Heart Failure
Modin, D., Jørgensen, M. E., Gislason, G., Jensen, J. S., Køber, L., Claggett, B. L., Hegde, S. M., Solomon, S. D., Torp-Pedersen, C. T., & Biering‐Sørensen, T. (2019) · Circulation · doi:10.1161/circulationaha.118.036788 · Cited by 178
AS03- and MF59-Adjuvanted Influenza Vaccines in Children
Wilkins, A. L., Kazmin, D. A., Napolitani, G., Clutterbuck, E., Pulendran, B., Siegrist, C., & Pollard, A. J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01760 · Cited by 164
“Hum Vaccin Immunother (2015) 11(2): 358–76.”
BackgroundHeikkinen, T., Ikonen, N., & Ziegler, T. T. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu664 · Cited by 151
Influenza-Associated Pediatric Deaths in the United States, 2004–2012
Wong, K. K., Jain, S., Blanton, L., Dhara, R., Brammer, L., Fry, A. M., & Finelli, L. (2013) · PEDIATRICS · doi:10.1542/peds.2013-1493 · Cited by 154
“Male gender 442 (53) Age, median (IQR), y 7 (1–12) ,6 months 94 (11) 6 to 23 months 114 (14) 24 to 59 months 117 (14) 5 to 8 years 167 (20) 9 to 12 years 112 (13) 13 to 17 years 226 (27) Race/ethnicity White 373 (45) Hispanic or Latino 194 (23) Black 149 (18) Asian 35 (4) American Indian/Alaska Native 17 (2) Native Ha…”
Su, S., Chaves, S. S., Pérez, A., D'Mello, T. A., Kirley, P. D., Yousey-Hindes, K. M., Farley, M. M., Harris, M. L., Sharangpani, R., Lynfield, R., et al. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu269 · Cited by 136
“influenza A and B virus in outpatient settings [1, 2] and substantial influenza B infections among pediatric influenza-associated fatalities [3].”
BackgroundHospitalization for Influenza A Versus B
Tran, D. T., Vaudry, W., MOORE, D. L., Bettinger, J. A., Halperin, S. A., Scheifele, D. W., Jadvji, T., Lee, L., Mersereau, T., & Active, F. T. M. O. T. C. I. M. P. (2016) · PEDIATRICS · doi:10.1542/peds.2015-4643 · Cited by 132
“Our study revealed that (1) influenza B accounted for at least one-third of influenza-associated hospitalizations in 4 of the 8 nonpandemic influenza seasons, with greater proportions during B vaccine-mismatched than during B vaccine-matched seasons; (2) children admitted with influenza B were older and more likely to…”
ResultNeuraminidase inhibitors for influenza B virus infection: Efficacy and resistance
Burnham, A. J., Baranovich, T., & Govorkova, E. A. (2013) · Antiviral Research · doi:10.1016/j.antiviral.2013.08.023 · Cited by 131
“Importantly, histological evidence of interstitial pneumonia and immunohistochemical features of alveoli involvements during influenza B virus infections was provided for fatal cases (Paddock et al., 2012).”
BackgroundInfluentialKnowns and Unknowns of Influenza B Viruses
Koutsakos, M., Nguyen, T. H. O., Barclay, W., & Kedzierska, K. (2015) · Future Microbiology · doi:10.2217/fmb.15.120 · Cited by 126
Liu, B., Li, N. L., Yang, S., Bao, X., Fabrizio, T. P., Elbahesh, H., Webby, R. J., & Li, K. (2016) · Journal of Virology · doi:10.1128/jvi.03172-15 · Cited by 112
Influenza B Viruses: Not to be Discounted
van de Sandt, C. E., Bodewes, R., Rimmelzwaan, G. F., & de Vries, R. D. (2015) · Future Microbiology · doi:10.2217/fmb.15.65 · Cited by 104
Burden of influenza B virus infection and considerations for clinical management
Zaraket, H., Hurt, A. C., Clinch, B., Barr, I., & Lee, N. L. S. (2020) · Antiviral Research · doi:10.1016/j.antiviral.2020.104970 · Cited by 100
Short, K. R., Habets, M. N., Hermans, P. W. M., & Diavatopoulos, D. A. (2012) · Future Microbiology · doi:10.2217/fmb.12.29 · Cited by 100
Gao, C., Wang, Y., Gu, X., Shen, X., Zhou, D., Zhou, S., Huang, J., Cao, B., Guo, Q., & for the Community-Acquired Pneumonia–China Network (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004207 · Cited by 89
“org April 2020 • Volume 48 • Number 4 injury (46).”
BackgroundKeilich, S. R., Bartley, J. M., & Haynes, L. (2019) · Cellular Immunology · doi:10.1016/j.cellimm.2019.103992 · Cited by 92
IFITM3 protects the heart during influenza virus infection
Kenney, A. D., McMichael, T. M., Imas, A., Chesarino, N. M., Zhang, L., Dorn, L. E., Wu, Q., Alfaour, O., Amari, F., Chen, M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900784116 · Cited by 81
“reported for up to 48% of fatal seasonal influenza cases (Oseasohn et al., 1959; Paddock et al., 2012; Ukimura et al., 2010; Ukimura et al., 2013), and a landmark autopsy study reported severe cardiac damage in a majority of 126 patients examined after succumbing to infection with the 1918 pandemic H1N1 influenza viru…”
BackgroundInfluentialCardiac Tropism of Borrelia burgdorferi
Muehlenbachs, A., Bollweg, B. C., Schulz, T., Forrester, J. D., DeLeon-Carnes, M., Molins, C. R., Ray, G. S., Cummings, P. M., Ritter, J. M., Blau, D. M., et al. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.12.027 · Cited by 81
“To evaluate for cardiomyocyte injury, IHC for complement components C4d and C9 was performed as previously described.(34,35) Mouse monoclonal antibodies against CD3 (M7254; Dako) and CD79a (sc20064; Santa Cruz Biotechnology) were used at 1:100 and 1:500 dilutions, respectively.”
MethodSelf-citationCollins, L. F., Anderson, B. D., & Gray, G. C. (2017) · Frontiers in Public Health · doi:10.3389/fpubh.2017.00001 · Cited by 80
Gutiérrez-Pizarraya, A., Pérez‐Romero, P., Álvarez‐Marín, R., Aydillo, T., Osorio-Gómez, G., Milara-Ibáñez, C., Sánchez, M., Pachón, J., & Cordero, E. (2012) · Journal of Infection · doi:10.1016/j.jinf.2012.07.004 · Cited by 80
McKimm‐Breschkin, J. L., Jiang, S., Hui, D. S. C., Beigel, J. H., Govorkova, E. A., & Lee, N. L. S. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.11.013 · Cited by 79
“In 45 cases of fatal influenza B histopathological findings of IAM were observed in 69% (20/29) of patients with cardiac samples available (Paddock et al., 2012) .”
BackgroundInfluenza and cardiovascular disease pathophysiology: strings attached
Skaarup, K. G., Modin, D., Nielsen, L., Jensen, J. S., & Biering‐Sørensen, T. (2023) · European Heart Journal Supplements · doi:10.1093/eurheartjsupp/suac117 · Cited by 75
“Direct myocardial mechanics Inflammation of myocardial tissue of influenza patients has been demonstrated, but only two of these studies could observe live influenza virus.(24,25,35,57) The number of studies on influenza-associated myocarditis in humans is limited; consequently, the pathology involved is poorly unders…”
ResultLangley, J. M., Martínez, A. C., Chatterjee, A., Halperin, S. A., McNeil, S., Reisinger, K. S., Aggarwal, N., Huang, L., Peng, C., García-Sicilia, J., et al. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit263 · Cited by 67
“Influenza B may also preferentially affect children and young adults [7], and has been associated with higher hospitalization rates in children than influenza A [8] and with particular clinical syndromes, including myocarditis [9–10].”
BackgroundLaurie, K., Horman, W. S. J., Carolan, L. A., Chan, K. F., Layton, D., Bean, A. G. D., Vijaykrishna, D., Reading, P. C., McCaw, J. M., & Barr, I. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix509 · Cited by 66
Fatal Influenza B Infections: Time to Reexamine Influenza Research Priorities
McCullers, J. A., & Hayden, F. G. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir865 · Cited by 65
Zheng, W., Fan, W., Zhang, S., Jiao, P., Shang, Y., Cui, L., Mahesutihan, M., Li, J., Wang, D., Gao, G. F., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.053 · Cited by 66
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“An autopsy report of patients who died from influenza B infection indicated that death often followed a remarkably rapid clinical progression, regardless of demonstrable bacterial pneumonia, and about 50 % of all patients died within 3 days after the onset of illness, with more than 70 % dying within 4 days [8].”
BackgroundLabella, A. M., & Merel, S. E. (2013) · Medical Clinics of North America · doi:10.1016/j.mcna.2013.03.001 · Cited by 61
Cardiovascular complications of acute respiratory infections: current research and future directions
Davidson, J. A., & Warren‐Gash, C. (2019) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2019.1689817 · Cited by 60
Predictors of influenza among older adults in the emergency department
Lam, P.-P., Coleman, B. L., Green, K., Powis, J. E., Richardson, D. C., Katz, K. C., Borgundvaag, B., Smith-Gorvie, T., Kwong, J. C., Bondy, S. J., et al. (2016) · BMC Infectious Diseases · doi:10.1186/s12879-016-1966-4 · Cited by 57
“More recent evidence has shown that influenza B is also capable of causing severe outcomes [30, 31] and similar clinical symptoms in adults [32].”
BackgroundRay, R., Santos, G. D., Buck, P. O., Claeys, C., Matias, G., Innis, B. L., & Bekkat-Berkani, R. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1313375 · Cited by 57
“could be hospitalised, highlighting the importance of vaccine prophylaxis in mitigating this risk.(54)”
BackgroundBurnham, A. J., Baranovich, T., Marathe, B. M., Armstrong, J., Webster, R. G., & Govorkova, E. A. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02628-13 · Cited by 52
“However, recent studies suggest that the role of influenza B viruses in human seasonal influenza is underestimated and that influenza A and B viruses have comparable rates of mortality in some epidemic seasons (1, 2).”
BackgroundAsai, N., Yokoi, T., Nishiyama, N., Koizumi, Y., Sakanashi, D., Kato, H., Hagihara, M., Suematsu, H., Yamagishi, Y., & Mikamo, H. (2017) · BMC Infectious Diseases · doi:10.1186/s12879-017-2677-1 · Cited by 52
Regional variation in mortality impact of the 2009 A ( H 1 N 1) influenza pandemic in C hina
Yu, H., Feng, S., Viboud, C. G., Shay, D. K., Jiang, Y., Zhou, H., Zhou, M., Xu, Z., Hu, N., Yang, W., et al. (2013) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12121 · Cited by 51
The Coming Era of Quadrivalent Human Influenza Vaccines
Barr, I., & Jelley, L. (2012) · Drugs · doi:10.2165/11641110-000000000-00000 · Cited by 47
Severe Complications in Influenza-like Illnesses
Mistry, R. D., Fischer, J. B., Prasad, P. A., Coffin, S. E., & Alpern, E. R. (2014) · PEDIATRICS · doi:10.1542/peds.2014-0505 · Cited by 46
Patel, M. C., Shirey, K. A., Boukhvalova, M. S., Vogel, S. N., & Blanco, J. C. G. (2018) · mBio · doi:10.1128/mbio.00246-18 · Cited by 48
“Substantial influenza B virus infections were noted among pediatric influenza-associated fatalities (40), and it has been suggested that oseltamivir may be less effective at reducing fever in outpatients infected with influenza B virus compared to influenza A virus (41).”
BackgroundVardeny, O., Udell, J. A., Joseph, J., Farkouh, M. E., Hernandez, A. F., McGeer, A., Talbot, H. K., Bhatt, D. L., Cannon, C. P., Goodman, S. G., et al. (2018) · American Heart Journal · doi:10.1016/j.ahj.2018.05.007 · Cited by 46
“More directly, influenza infection has also been associated with myocardial depression,(36) which has been ascribed to an increase in proinflammatory cytokines,(37,38) and autopsy series have documented histologic evidence of myocardial injury, myocarditis, and myocyte necrosis following influenza-related deaths.(39)…”
Barr, I., Vijaykrishna, D., & Sullivan, S. G. (2016) · Eurosurveillance · doi:10.2807/1560-7917.es.2016.21.4.30118 · Cited by 44
“on deaths attributed to confirmed influenza B in the US from 2000 to 2010, the majority of subjects were 18 years and younger (34/45 cases), and a slightly higher proportion of infections were B/Vic compared with B/Yam (25 vs 17 deaths, respectively, in those cases that could be characterised) [11].”
BackgroundFountoulaki, K., Tsiodras, S., Polyzogopoulou, E., Olympios, C. D., & Parissis, J. (2018) · Cardiology · doi:10.1159/000493572 · Cited by 46
Influenza virus replication in cardiomyocytes drives heart dysfunction and fibrosis
Kenney, A. D., Aron, S. L., Gilbert, C., Kumar, N., Chen, P., Eddy, A. C., Zhang, L., Zani, A., Vargas-Maldonado, N., Speaks, S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abm5371 · Cited by 42
Influenza vaccination: a one-shot deal to reduce cardiovascular events
Vardeny, O., & Solomon, S. D. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw560 · Cited by 39
“Moreover, influenza is known to cause myocardial depression directly,(7) possibly mediated through increases in proinflammatory cytokines,(8,9) and histological evidence of myocardial injury, myocarditis, and myocyte necrosis has been demonstrated from patients following influenza-related deaths.(10)”
BackgroundBassetti, M., Giacobbe, D. R., Aliberti, S., Barisione, E., Centanni, S., Rosa, F. G. D., Marco, F. D., Gori, A., Granata, G., Mikulska, M., et al. (2020) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2020.04.031 · Cited by 40
“Common bacteria implicated were Staphylococcus aureus , including methicillin-resistant strains [51], Streptococcus pneumoniae, Haemophilus in fl uenzae and group A streptococci [49,52,53].”
Carolan, L. A., Rockman, S., Borg, K., Guarnaccia, T. A., Reading, P. C., Mosse, J., Kelso, A., Barr, I., & Laurie, K. (2015) · Journal of Virology · doi:10.1128/jvi.02797-15 · Cited by 39
“tions indicated that influenza B viruses accounted for 30 to 40% of the burden of severe disease in children (5).”
BackgroundEpidemiology of influenza B in Australia: 2001‐2014 influenza seasons
Moa, A., Muscatello, D. J., Turner, R. M., & MacIntyre, C. R. (2016) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12432 · Cited by 38
A comprehensive review of influenza B virus, its biological and clinical aspects
Ashraf, M. A., Raza, M. A., Amjad, M., Din, G. U., Yue, L., Shen, B., Chen, L., Wei, D., Xu, H., & Hu, Y. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1467029 · Cited by 42
Habel, J. R., Nguyen, A., Rowntree, L. C., Szeto, C. W., Mifsud, N. A., Clemens, E. B., Loh, L., Chen, W., Rockman, S., Nelson, J., et al. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010337 · Cited by 35
“IBVs can also lead to severe neurological, cardiovascular and muscular complications [41] and secondary bacterial pneumonia [41,42].”
BackgroundUS healthcare costs attributable to type A and type B influenza
Yan, S., Weycker, D. A., & Sokolowski, S. S. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1345400 · Cited by 36
“The limited evidence that does exist suggests that when influenza type B activity is heightened, the impact on mortality and hospitalizations is comparable to that of influenza type A, and that the clinical and cost burden of influenza type B has increased in recent years.(6,7,8) A better understanding of the populati…”
Quadrivalent Ann Arbor strain live-attenuated influenza vaccine
Toback, S. L., Levin, M. J., Block, S. L., Belshe, R. B., Ambrose, C. S., & Falloon, J. (2012) · Expert Review of Vaccines · doi:10.1586/erv.12.108 · Cited by 35
Jain, V. K., Domachowske, J. B., Wang, L., Ofori‐Anyinam, O., Weber, M., Leonardi, M. L., Klein, N. P., Schlichter, G., Jeanfreau, R. J., Haney, B. L., et al. (2016) · Journal of the Pediatric Infectious Diseases Society · doi:10.1093/jpids/piw068 · Cited by 35
“Increased protection against influenza B, a potentially serious and life-threatening illness particularly in young children [33], would be a beneficial clinical outcome.”
BackgroundHékimian, G., Jovanovic, T., Bréchot, N., Lebreton, G., Leprince, P. N., Trouillet, J., Schmidt, M., Nieszkowska, A., Besset, S., Chastre, J. E., et al. (2018) · Journal of Critical Care · doi:10.1016/j.jcrc.2018.06.001 · Cited by 34
Pulmonary complications of influenza infection: a targeted narrative review
Daoud, A., Laktineh, A., Macrander, C., Mushtaq, A., & Soubani, A. O. (2019) · Postgraduate Medicine · doi:10.1080/00325481.2019.1592400 · Cited by 32
“Studies of Influenza B have found similar pathogens [79].”
BackgroundYang, C., Wang, Y., He, J., Yan, W., Jiang, H., Chen, Q., Li, L., & Yang, Z. (2020) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2020/3196375 · Cited by 31
“Furthermore, influenza B virus caused more complications, including neurological, muscular manifestations [4, 5] and cardiologic complications [6, 7].”
BackgroundRetractedHong, K., Cheong, H. J., Song, J. Y., Noh, J. Y., Yang, T. U., & Kim, W. J. (2014) · Japanese Journal of Infectious Diseases · doi:10.7883/yoken.jjid.2013.466 · Cited by 30
Deleterious effects of viral pneumonia on cardiovascular system
Duan, J., Wu, Y., Liu, C., Yang, C., & Yang, L. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa325 · Cited by 30
Pizzini, A., Burkert, F. R., Theurl, I., Weiß, G., & Bellmann‐Weiler, R. (2019) · Heart & Lung · doi:10.1016/j.hrtlng.2019.05.009 · Cited by 29
Bal, A., Casalegno, J., Melenotte, C., Daviet, F., Ninove, L., Edouard, S., Morfin, F., Valette, M., de Lamballerie, X. N., Lina, B., et al. (2020) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2020.03.010 · Cited by 28
Song, Y., Gao, P., Ran, T., Qian, H., Guo, F., Chang, L., Wu, W., & Zhang, S. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00128 · Cited by 28
“arrhythmias and sudden death in patients with viral infectious diseases, which are associated with adverse events and a high mortality rate (13, 14).”
BackgroundPost-influenza aspergillosis, do not underestimate influenza B
Nulens, E., Bourgeois, M., & Reynders, M. (2017) · Infection and Drug Resistance · doi:10.2147/idr.s122390 · Cited by 27
Garg, S., Moore, Z., Lee, N., McKenna, J. J., Bishop, A. M., Fleischauer, A. T., Springs, C. B., Nguyen, H., Sheu, T. G., Sleeman, K., et al. (2012) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis776 · Cited by 27
“Influenza B viruses cause annual epidemics and can be associated with severe disease resulting in hospitalizations and deaths [1–3].”
BackgroundReverse Genetics of Influenza B Viruses
Nogales, A., Perez, D. R., Santos, J. J. D. S., Finch, C. L., & Martínez‐Sobrido, L. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6964-7_14 · Cited by 27
Liu, Y., Yang, Y., Fan, J., He, R., Luo, M., & Zheng, X. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.636464 · Cited by 25
“Influenza B virus has a devastating mortality rate in humans, especially in children (3, 4, 6), which is an essential characteristic of seasonal influenza.”
BackgroundOwusu, D., Hand, J., Tenforde, M. W., Feldstein, L. R., DaSilva, J. C., Barnes, J., Lee, G., Tran, J., Sokol, T. M., Fry, A. M., et al. (2020) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6902e1 · Cited by 24
Teutsch, S. M., Zurynski, Y. A., Nunez, C. A., Lester‐Smith, D., Festa, M., Booy, R., Elliott, E. J., & Unit, F. T. A. P. S. (2020) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000002961 · Cited by 24
“Although seasonal influenza epidemics and pandemics are usually attributed to influenza A, due to its capacity for rapid antigenic change, influenza B may also have an important role to play in contributing to disease burden.(27,28) In our study, influenza A and B coexisted variably from season to season, as previousl…”
BackgroundIncidence and risk factors of myocarditis in hospitalized patients with COVID‐19
Keller, K., Sagoschen, I., Konstantinides, S., Gori, T., Münzel, T. F., & Hobohm, L. (2023) · Journal of Medical Virology · doi:10.1002/jmv.28646 · Cited by 23
“between other infections, such as pneumonia as well as multisystemic inflammatory COVID‐19 infection and myocarditis.(14,52) This is an important finding since mortality in COVID‐19 patients has been linked to a “cytokine storm” induced by the SARS‐CoV‐2.”
BackgroundÖzbay, S., Ayan, M., Özsoy, O., Akman, C., & Karcıoğlu, Ö. (2023) · Diagnostics · doi:10.3390/diagnostics13111869 · Cited by 24
“S. aureus is one of the most common bacterial infections associated with influenza pneumonia, followed by S. pneumoniae, H. influenzae, and Group A Streptococcus [100,101].”
InfluentialClinical characteristics and outcomes during a severe influenza season in China during 2017–2018
Fu, X., Zhou, Y., Wu, J., Liu, X., Ding, C., Huang, C., Zheng, S., Vijaykrishna, D., Chen, Y., Li, L., et al. (2019) · BMC Infectious Diseases · doi:10.1186/s12879-019-4181-2 · Cited by 22
Innate and Adaptive Immunity Toward Influenza B Viruses
Hensen, L., Kedzierska, K., & Koutsakos, M. (2020) · Future Microbiology · doi:10.2217/fmb-2019-0340 · Cited by 22
Vita, A. D., Ravenna, S. E., Covino, M., Lanza, O., Franceschi, F., Crea, F., & Lanza, G. A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9113647 · Cited by 22
“However, it is not known whether the prevalence of cardiac involvement is increased in COVID-19 as compared to other acute infectious respiratory diseases (AIRDs), which have also been reported to be associated with myocardial injury in a sizeable proportion of patients [15,16].”
BackgroundBurnham, A. J., Armstrong, J., Lowen, A. C., Webster, R. G., & Govorkova, E. A. (2015) · Journal of Virology · doi:10.1128/jvi.02473-14 · Cited by 22
Influenza Causes MLKL-Driven Cardiac Proteome Remodeling During Convalescence
Lin, Y.-H., Platt, M. P., Gilley, R. P., Brown, D., Dube, P. H., Yu, Y., & González-Juarbe, N. (2021) · Circulation Research · doi:10.1161/circresaha.120.318511 · Cited by 22
Influenza-associated bacterial pneumonia; managing and controlling infection on two fronts
Campigotto, A. J., & Mubareka, S. (2014) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.2015.981156 · Cited by 23
Does influenza vaccination influence cardiovascular complications?
Udell, J. A., Farkouh, M. E., Solomon, S. D., & Vardeny, O. (2015) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.2015.1044439 · Cited by 20
“Influenza can act to produce a potent inflammatory and thrombotic stimulus, with either direct myocardial injury or indirect influence by activation of circulating procoagulants, elevation in cytokine levels, endothelial dysfunction, fluid shifts and sympathetic stimulation as observed in patients with coronary artery…”
BackgroundInfluenza B-induced refractory cardiogenic shock: a case report
Taremi, M., Amoroso, A., Nace, H., & Gilliam, B. L. (2013) · BMC Infectious Diseases · doi:10.1186/1471-2334-13-452 · Cited by 20
“Influenza B virus infection is generally considered to be mild with less associated cardiovascular involvement in adults [7].”
Miron, V. D., Săndulescu, O., Streinu‐Cercel, A., Florea, D., Paraschiv, S., Bănică, L. M., Vlaicu, O., Oţelea, D., Bilașco, A., Pițigoi, D., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-66550-8 · Cited by 19
Sieweke, J., Akin, M., Stetskamp, S., Riehle, C., Jonigk, D. D., Flierl, U., Pfeffer, T. J., Hirsch, V. G., Dutzmann, J., Hoeper, M. M., et al. (2020) · European Respiratory Journal · doi:10.1183/13993003.00925-2020 · Cited by 21
In vitro evaluation of the antiviral activity of methylglyoxal against influenza B virus infection
Charyasriwong, S., Haruyama, T., & Kobayashi, N. (2016) · Drug Discoveries & Therapeutics · doi:10.5582/ddt.2016.01045 · Cited by 19
“Clinical reports also have shown that infection by influenza B viruses tends to induce lethal secondary bacterial infections and myocardial or neurological complications (3-6).”
BackgroundMook, P. A., Meerhoff, T. J., Olsen, S. J., Snacken, R., Adlhoch, C., Pereyaslov, D. I., Broberg, E., Melidou, A., Brown, C., Penttinen, P. M., et al. (2020) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12703 · Cited by 19
Identification and characterization of viral defective RNA genomes in influenza B virus
Sheng, Z., Liu, R., Yu, J., Ran, Z., Newkirk, S. J., An, W., Li, F., & Wang, D. (2018) · Journal of General Virology · doi:10.1099/jgv.0.001018 · Cited by 18
“The burden of respiratory diseases caused by FLUBV, coupled with the increasing strong links between FLUBV and fatal infections in humans [11, 12], calls for an urgent need for more basic and clinical investigations of FLUBV.”
BackgroundAntiviral activity of KR-23502 targeting nuclear export of influenza B virus ribonucleoproteins
Jang, Y., Lee, H. W., Shin, J. S., Go, Y. Y., Kim, C., Shin, D., Malpani, Y. R., Han, S. B., Jung, Y., & Kim, M. (2016) · Antiviral Research · doi:10.1016/j.antiviral.2016.07.024 · Cited by 18
Speers, D. J., Moss, D. M., Minney-Smith, C. A., Levy, A., & Smith, D. W. (2013) · Influenza and Other Respiratory Viruses · doi:10.1111/irv.12139 · Cited by 18
Prospective comparative study of characteristics associated with influenza A and B in adults
Chagvardieff, A., Persico, N., Marmillot, C., Badiaga, S., Charrel, R. N., & Roch, A. (2017) · Médecine et Maladies Infectieuses · doi:10.1016/j.medmal.2017.11.007 · Cited by 15
The Development and Use of Reporter Influenza B Viruses
Dumm, R. E., & Heaton, N. S. (2019) · Viruses · doi:10.3390/v11080736 · Cited by 17
Chu, K., Xu, K., Tang, R., Tian, X., Hu, J., Yang, T., Li, C., Hu, Y., & Zeng, G. (2020) · Vaccine · doi:10.1016/j.vaccine.2020.06.071 · Cited by 17
Lei, N., Wang, H., Zhang, Y., Zhao, J., 田中, 義., Wang, Y., Huang, L., Ma, J., Sun, Q., Yang, L., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-38105-1 · Cited by 16
Denison, A. M., DeLeon-Carnes, M., Blau, D. M., Shattuck, E. C., McDougal, L. K., Rasheed, J. K., Limbago, B. M., Zaki, S. R., & Paddock, C. D. (2013) · Journal of Clinical Microbiology · doi:10.1128/jcm.02503-13 · Cited by 15
“Influenza viruses target and destroy ciliated epithelial cells that line airways, as well as mucous gland epithelium, resulting in a markedly diminished mucociliary clearance of bacteria that might otherwise be expelled from a normally functioning lung (13).”
BackgroundSelf-citationMarathe, B. M., Mostafa, H. H., Vogel, P., Pascua, P. N. Q., Jones, J. C., Russell, C. J., Webby, R. J., & Govorkova, E. A. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.10.021 · Cited by 15
“Influenza B virus infections are clinically indistinguishable from influenza A virus infections, but the associated complications may differ (Koutsakos et al., 2016) and may include encephalitis, encephalopathy, gastrointestinal symptoms, or myositis (Burnham et al., 2013; Paddock et al., 2012).”
Self-Reported Depression of Cancer Patients Under 2019 Novel Coronavirus PandemicPreprint
Zheng, X., Tao, G., Huang, P. C., He, F., Shao, X., Xu, Y., Zhong, L., & Yang, G. (2020) · SSRN Electronic Journal · doi:10.2139/ssrn.3555252 · Cited by 16
“Myocardial involvement is not uncommon with severe influenza A or B virus infection, and multiple studies have shown an association between influenza and acute myocardial infection and myocarditis [66] [67] [68] .”
BackgroundJennings, Z., Carter, I. W. J., McPhie, K. A., Kok, J., & Dwyer, D. E. (2015) · Eurosurveillance · doi:10.2807/1560-7917.es2015.20.31.21201 · Cited by 14
Amad, M. A. A., Mahaqri, A. A. A., Serouri, A. A. A., & Khader, Y. S. (2019) · INQUIRY The Journal of Health Care Organization Provision and Financing · doi:10.1177/0046958019850731 · Cited by 14
“23, 24 Similar to findings of a study in Egypt, 18 chronic diseases were found to be associated with fatality outcome.”
ResultInfluenza at the beginning of the 21st century
Shindo, N., & Briand, S. C. (2012) · Bulletin of the World Health Organization · doi:10.2471/blt.12.104653 · Cited by 14
Chien, S., Hsieh, Y.-J., Shih, Y.-L., & Tseng, Y. (2022) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2022.03.002 · Cited by 12
The Epidemiology and Burden of Influenza B/Victoria and B/Yamagata Lineages in Kenya, 2012–2016
Emukule, G. O., Otiato, F., Nyawanda, B. O., Otieno, N. A., Ochieng, C. A., Ndegwa, L., Muturi, P., Bigogo, G., Verani, J. R., Muthoka, P. M., et al. (2019) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofz421 · Cited by 12
A Fatal Case of Influenza B Myocarditis with Cardiac Tamponade
Roto, D., Malnoske, M., Winters, S. M., & Georas, S. N. (2018) · Case Reports in Critical Care · doi:10.1155/2018/8026314 · Cited by 12
Korem, M., Orenbuch‐Harroch, E., Ben‐Chetrit, E., Israel, S., Cohen, M. J., Sviri, S., Levin, P. D., Mandelboim, M., & Wolf, D. G. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciz053 · Cited by 12
Metadata
- 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)
- 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
- 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
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