Cited by 429Influenza Virus Research StudiesRespiratory viral infections researchCOVID-19 Clinical Research Studies

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index; none of the 24 sources its claims cite is checked for support yet.

Pulmonary Pathologic Findings of Fatal 2009 Pandemic Influenza A/H1N1 Viral Infections

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Abstract

Context: In March 2009, a novel swine-origin influenza A/H1N1 virus was identified. After global spread, the World Health Organization in June declared the first influenza pandemic in 41 years. Objective: To describe the clinicopathologic characteristics of 34 people who died following confirmed A/H1N1 infection with emphasis on the pulmonary pathology findings. Design: We reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides of 34 people who died between May 15 and July 9, 2009, and were investigated either by the New York City Office of Chief Medical Examiner (32 deaths) or through the consultation service of a coauthor (2 deaths). Results: Most of the 34 decedents (62%) were between 25 and 49 years old (median, 41.5 years). Tracheitis, bronchiolitis, and diffuse alveolar damage were noted in most cases. Influenza viral antigen was observed most commonly in the epithelium of the tracheobronchial tree but also in alveolar epithelial cells and macrophages. Most cases were reverse transcription–polymerase chain reaction positive for influenza. Histologic and microbiologic autopsy evidence of bacterial pneumonia was detected in 55% of cases. Underlying medical conditions including cardiorespiratory diseases and immunosuppression were present in 91% of cases. Obesity (body mass index, >30) was noted in 72% of adult and adolescent cases. Conclusions: The pulmonary pathologic findings in fatal disease caused by the novel pandemic influenza virus are similar to findings identified in past pandemics. Superimposed bacterial infections of the respiratory tract were common. Preexisting obesity, cardiorespiratory diseases, and other comorbidities also were prominent findings among the decedents.

Overview

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TL;DR

In 34 fatal 2009 pandemic A/H1N1 cases, pulmonary pathology showed tracheitis/bronchitis in all and diffuse alveolar damage in 25 of 34, with viral antigen mainly in tracheobronchial epithelium and macrophages. Bacterial pneumonia was found in 55%, and 91% of adult/adolescent decedents had underlying risk factors, including obesity in 72%.

Key findings

  • Among 34 decedents, 62% were 25 to 49 years old (median, 41.5 years); there were 2 previously healthy infants aged 2 and 4 months and 1 person older than 60 years.
  • Tracheitis and bronchitis were observed in all cases; bronchiolitis in 18 of 34; diffuse alveolar damage in 25 of 34; acute pulmonary hemorrhage in 8 of 34; and thrombotic changes in 9 of 34.
  • Novel A/H1N1 virus was detected antemortem or at autopsy in all 34 decedents: 28 (82%) by real-time RT-PCR on postmortem nasopharyngeal and/or tracheal swabs and 23 of 34 (68%) by RT-PCR on FFPE lung and/or tracheal tissues.
  • Autopsy evidence of acute pneumonia was seen in 19 of 34 cases (56%); tissue Gram stain showed bacterial pneumonia in 18 of 33 (55%), and 29 of 32 adult decedents (91%) had underlying risk factors, with obesity (BMI ≥30) in 72% of adult and adolescent decedents.

Methods

  • Retrospective case series of 34 people who died between May 15 and July 9, 2009, with confirmed novel A/H1N1 infection: 32 investigated by the New York City Office of Chief Medical Examiner and 2 seen in consultation from Washington State and Long Island, New York.
  • Reviewed medical records, autopsy reports, microbiologic studies, and microscopic slides; histologic examination used hematoxylin-eosin, Gomori methenamine silver, and Brown and Hopps tissue Gram stains.
  • Viral studies included real-time RT-PCR on nasopharyngeal/tracheal swabs and FFPE autopsy tissue, plus immunohistochemistry for influenza A viral antigen; CT imaging was available for 4 patients.

Limitations

  • Stated in the paper: there is insufficient clinical information about the natural history of severe influenza disease to fully inform optimal prophylaxis and treatment approaches.
  • Stated in the paper: bacterial detection may be limited by inadequate sampling, collection from unaffected lung portions, or prolonged illness/treatment; it is also unknown whether CT abnormalities or pulmonary pathologic changes occur in milder or self-limited infections.
  • Evident from the text: this is a small, retrospective autopsy/consultation case series without a control group, drawn from deaths investigated by a medical examiner’s office and selected consultations, so findings may not generalize to all A/H1N1 infections.

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Integrity signals

Registry

Crossref · 10.5858/134.2.235

Cites

39 of 39 references verified0 citation errors · 0 not checkable

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38 Own result · 15 Not checked yet · 6 Own interpretation

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  • It may state two separate claims as one. 11
  • The quote only partly states this claim. 2
  • Probably not a substantial claim. 4
15 of 15
  • The paper relies on this without support.

    The 34 investigated deaths are representative of fatal 2009 pandemic influenza A/H1N1 infections.

    “We investigated 34 deaths with confirmed novel A/H1N1 respiratory infection, reviewing available clinical, radiologic, pathologic, and microbiologic data.”
  • The paper relies on this without support.

    Autopsy histologic and microbiologic findings accurately reflect the pulmonary disease process that caused death.

    “The decision by the New York City Office of Chief Medical Examiner to investigate deaths associated with infection by the 2009 pandemic influenza virus provides an opportunity to examine the pathogenesis of fatal pandemic influenza.”
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Citations

Cites

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Research works printed but not linked: 26

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Metadata

Authors
Gill, J. R., Sheng, Z.-M., Ely, S. F., Guinee, D. G., Beasley, M. B., Suh, J., Deshpande, C., Mollura, D. J., Morens, D. M., Bray, M., Travis, W. D., & Taubenberger, J. K.
Affiliations
  • Office of Chief Medical Examiner (US)
  • National Institutes of Health (US)
Venue
Archives of Pathology & Laboratory Medicine
Published
2010-02
Volume
134
Issue
2
Pages
235-243
ISSN
  • 0003-9985 (ISSN-L)
  • 1543-2165
OpenAlex
W1852307476
Cited by
426
References
39
Citations by year
2026: 5 · 2025: 8 · 2024: 12 · 2023: 16 · 2022: 16 · 2021: 38 · 2020: 23 · 2019: 22 · 2018: 19 · 2017: 10 · 2016: 13 · 2015: 22 · 2014: 21 · 2013: 31 · 2012: 57
FWCI
46.91
Type
journal article
Language
en
Open access
Locations
  • Archives of Pathology & Laboratory Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (ZIAAI000986)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
2009 H1N1 pandemic, H1N1 influenza, fatal influenza, lung pathology, secondary bacterial infection, bacterial pneumonia, tracheitis, bronchiolitis, diffuse alveolar damage, obesity, comorbidities, cardiopulmonary disease, immunosuppression, autopsy findings
MeSH terms
Adolescent, Adult, Aged, Child, Child, Preschool, Disease Outbreaks, Female, Humans, Infant, Infant, Newborn, Influenza, Human, Lung, Male, Middle Aged, Radiography, Time Factors, Comorbidity, Pneumonia, Bacterial, Influenza A Virus, H1N1 Subtype

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