Adenovirus Respiratory Infection

Infectious Disease Pathograph 16 Show in embeddings browser Viral Respiratory Infection

Adenovirus respiratory infection is an acute infection caused by human adenoviruses, non-enveloped double-stranded DNA viruses with type-dependent tissue tropism. Most disease in immunocompetent people is mild and self-limited, but adenovirus can cause pharyngitis, conjunctivitis, and lower respiratory infection. Severe pneumonia occurs particularly in young children, crowded congregate settings such as military training, and people with impaired immunity; survivors of severe pediatric pneumonia can develop chronic respiratory sequelae including bronchiolitis obliterans.

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6
Pathophys.
9
Phenotypes
16
Pathograph
3
Medical Actions
3
Differentials
1
Datasets
⚙

Pathophysiology

6
Adenoviral DNA Polymerase Activity
Adenoviral DNA polymerase copies the double-stranded DNA genome. The active diphosphorylated metabolite of cidofovir interacts with viral DNA polymerase, making this replication step a pharmacologic vulnerability, although clinical evidence for cidofovir in adenovirus disease remains limited.
viral genome replication GO:0019079 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves viral genome replication (GO:0019079). GO:0019079 is a biological process from the Gene Ontology.
nucleotidyltransferase activity GO:0016779 Gene Ontology (GO) Relation: this pathophysiological event involves this molecular function This pathophysiological event involves nucleotidyltransferase activity (GO:0016779). GO:0016779 is a molecular function from the Gene Ontology.
Downstream
Respiratory Epithelial Infection and Viral Replication Viral DNA synthesis supports productive replication in infected respiratory epithelial cells.
Show evidence (1 reference)
PMID:8701600 SUPPORT Other
"The mechanism of action of HPMPC is based upon the interaction of its active intracellular metabolite, the diphosphorylated HPMPC derivative HPMPCpp, with the viral DNA polymerase."
This review directly identifies viral DNA polymerase as the molecular target of active cidofovir metabolite.
Respiratory Epithelial Infection and Viral Replication
Human adenovirus infects respiratory epithelial cells and replicates its DNA genome. Respiratory infection is usually mild and self-limited in immunocompetent hosts, but type and host context influence whether disease remains localized or progresses to pneumonia.
respiratory epithelial cell CL:0002632 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves respiratory epithelial cell, annotated with epithelial cell of lower respiratory tract (CL:0002632). CL:0002632 is a cell type from the Cell Ontology. ciliated airway epithelial cell CL:0002145 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves ciliated airway epithelial cell, annotated with multiciliated columnar cell of tracheobronchial tree (CL:0002145). CL:0002145 is a cell type from the Cell Ontology.
viral genome replication GO:0019079 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves viral genome replication (GO:0019079). GO:0019079 is a biological process from the Gene Ontology.
respiratory system UBERON:0001004 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in respiratory system (UBERON:0001004). UBERON:0001004 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Innate Antiviral Response Entry and genome replication expose viral components to cellular innate recognition pathways, including DNA sensors that trigger interferon.
Airway Pro-inflammatory Cytokine Response Adenovirus type 7 infection activates p38/NF-kappaB signaling in airway epithelial cells and increases airway inflammatory cytokines.
Conjunctivitis Human adenovirus mucosal tropism includes conjunctival infection; the cited spectrum evidence does not establish co-occurrence with the respiratory syndrome in the same patients.
Show evidence (2 references)
PMID:27486739 SUPPORT Other
"Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva."
This review establishes adenovirus infection of upper and lower respiratory sites and its usually mild clinical course.
PMID:33072092 SUPPORT In Vitro
"AdV 7 infection of bronchial epithelial cell line and primary airway epithelial cells confirmed that AdV 7 increased IL-6 mRNA and protein expression in an infection dose-dependent manner."
Infection experiments directly establish adenovirus type 7 infection of bronchial and primary airway epithelial cells.
Innate Antiviral Response
Intrinsic restriction factors, pattern-recognition receptors, and cytosolic DNA sensors mount an antiviral response to adenovirus and trigger interferon. Adenovirus early proteins and virus-associated RNAs counter several of these defenses, so the net response varies by cell and host context.
antiviral innate immune response GO:0140374 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves antiviral innate immune response (GO:0140374). GO:0140374 is a biological process from the Gene Ontology. defense response to virus GO:0051607 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves defense response to virus (GO:0051607). GO:0051607 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:24512150 SUPPORT Other
"Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine..."
This review supports cytosolic restriction and DNA-sensor-driven interferon responses to adenovirus.
Airway Pro-inflammatory Cytokine Response
In airway samples from children with adenovirus type 7 infection, multiple inflammatory cytokines are elevated. In airway epithelial models, infection activates p38/NF-kappaB signaling and IL-6 expression; excessive inflammation is a plausible contributor to tissue injury and severe symptoms.
respiratory epithelial cell CL:0002632 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves respiratory epithelial cell, annotated with epithelial cell of lower respiratory tract (CL:0002632). CL:0002632 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
respiratory system UBERON:0001004 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in respiratory system (UBERON:0001004). UBERON:0001004 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Upper Respiratory Clinical Syndrome Airway infection and inflammation manifest clinically with prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation.
Cough Airway inflammation during pediatric adenovirus pneumonia commonly produces cough.
Severe Adenovirus Pneumonia and Lung Injury Direct viral injury and an excessive inflammatory response can converge on severe lower-respiratory disease, although the determinants of progression are incompletely resolved.
Show evidence (1 reference)
PMID:33072092 SUPPORT Human Clinical
"Our results showed that eight out of 13 tested inflammatory cytokines were significantly increased in nasal washes of AdV 7-infected children comparing to healthy control, with IL-6 showing the highest enhancement."
Patient airway samples directly support a broad pro-inflammatory response in adenovirus type 7 infection.
Upper Respiratory Clinical Syndrome
Respiratory adenovirus infection often produces a febrile pharyngitis syndrome with nasal congestion; the phenotype combination can resemble other viral respiratory infections.
respiratory system UBERON:0001004 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in respiratory system (UBERON:0001004). UBERON:0001004 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Fever Confirmed respiratory adenovirus infection is associated with high, often prolonged fever.
Pharyngitis Sore throat and pharyngeal inflammation constitute adenoviral pharyngitis.
Nasal Congestion Nasal congestion accompanies the febrile respiratory syndrome.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"High and prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation were significantly more common in the HAdV pneumonia group, compared to patients with other or unknown causes of pneumonia."
The outbreak cohort supports the defining febrile upper-airway symptom cluster.
Severe Adenovirus Pneumonia and Lung Injury
A minority of respiratory infections progress to severe lower-respiratory disease with extensive inflammatory lung injury. Severe pediatric pneumonia can require ventilatory support and may be followed by chronic small-airway obstruction, especially bronchiolitis obliterans.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology. ↑ INCREASED
lung UBERON:0002048 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lung (UBERON:0002048). UBERON:0002048 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Pneumonia Lower-respiratory adenovirus infection produces clinically confirmed viral pneumonia.
Dyspnea Severe pediatric adenovirus pneumonia can present with dyspnea and systemic toxicity.
Respiratory Failure A subset of adenovirus pneumonia progresses to respiratory failure.
Bronchiolitis Obliterans Severe childhood adenovirus pneumonia can be followed by chronic obliterative small-airway disease.
Show evidence (1 reference)
PMID:30321228 SUPPORT Human Clinical
"One in five children admitted with HAdV pneumonia had severe disease and 22% developed respiratory complications."
This hospitalized pediatric cohort quantifies severe disease and later respiratory complications.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Adenovirus Respiratory Infection Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

9
Cardiovascular 1
Conjunctivitis HP:0000509 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Conjunctivitis (HP:0000509). HP:0000509 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27486739 SUPPORT Other
"Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva."
This review directly supports conjunctival involvement.
Head and Neck 1
Nasal Congestion HP:0001742 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Nasal congestion (HP:0001742). HP:0001742 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"High and prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation were significantly more common in the HAdV pneumonia group, compared to patients with other or unknown causes of pneumonia."
The prospective outbreak cohort directly supports nasal congestion.
Immune 1
Pneumonia HP:0002090 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pneumonia (HP:0002090). HP:0002090 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"HAdV pneumonia infected recruit trainees most frequently."
Etiologic testing documented an adenovirus pneumonia outbreak.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"High and prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation were significantly more common in the HAdV pneumonia group, compared to patients with other or unknown causes of pneumonia."
The prospective outbreak cohort directly supports fever.
Respiratory 4
Pharyngitis HP:0025439 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pharyngitis (HP:0025439). HP:0025439 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"High and prolonged fever, nasal congestion, sore throat, and pharyngeal inflammation were significantly more common in the HAdV pneumonia group, compared to patients with other or unknown causes of pneumonia."
The prospective outbreak cohort directly supports pharyngeal inflammation.
Cough HP:0012735 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cough (HP:0012735). HP:0012735 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:34712627 SUPPORT Human Clinical
"All patients had cough, and 116 (92.8%) patients with mild cases and 82 (95.4%) patients with severe cases had varying degrees of fever."
Cough was present in all children in this hospitalized pneumonia cohort.
Dyspnea HP:0002094 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dyspnea (HP:0002094). HP:0002094 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37476615 SUPPORT Other
"Early clinical recognition depends on patients' symptoms and laboratory tests, including those under 2 years old, dyspnea with systemic toxic symptoms, atelectasis or emphysema in CT image, decreased leukocytes, and significantly increased C-reaction protein (CRP) and procalcitonin (PCT),..."
This review identifies dyspnea as an indicator of severe disease.
Respiratory Failure HP:0002878 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory failure (HP:0002878). HP:0002878 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"HAdV pneumonia exhibited specific laboratory and clinical features, and although most patients were cured without complication, some progressed to respiratory failure and fatality."
The prospective outbreak cohort documents respiratory failure.
Other 1
Bronchiolitis Obliterans HP:0011946 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bronchiolitis obliterans (HP:0011946), qualified as temporality chronic. HP:0011946 is a phenotype from the Human Phenotype Ontology.
Temporal: CHRONIC
Show evidence (1 reference)
PMID:30321228 SUPPORT Human Clinical
"Twenty-two percent developed respiratory complications, the commonest being bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%)."
This follow-up cohort directly supports bronchiolitis obliterans as a sequela.
💊

Medical Actions

3
Supportive and Respiratory Care
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Most respiratory adenovirus infections are self-limited. Severe pneumonia may require supplemental oxygen, ventilatory support, and other organ support; no adenovirus-specific drug is approved.
Show evidence (2 references)
PMID:37476615 SUPPORT Other
"Until now, there is no specific drug for adenovirus pneumonia, so in clinical practice, current treatment comprises antiviral drugs, respiratory support and bronchoscopy, immunomodulatory therapy, and blood purification."
The pediatric review supports respiratory and organ-supportive management in severe disease.
PMID:28114362 SUPPORT Human Clinical
"Most patients in our study were treated empirically with antibiotics, and most HAdV pneumonia cases were self-limiting without an antiviral agent."
This outbreak cohort supports the self-limited course in most immunocompetent patients.
Intravenous Cidofovir for Selected Severe Disease
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: cidofovir NCIT:C1600 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses cidofovir (NCIT:C1600). NCIT:C1600 is a therapeutic agent from the NCI Thesaurus.
Intravenous cidofovir is used off label in some transplant centers for severe, progressive, or disseminated adenovirus disease. This is not an approved general treatment for uncomplicated respiratory infection, prospective randomized efficacy data are absent, and nephrotoxicity limits use.
Mechanism Target:
INHIBITS Adenoviral DNA Polymerase Activity — Intracellular cidofovir diphosphate interacts with viral DNA polymerase, and cidofovir inhibits replication across tested adenovirus serotypes in vitro.
Show evidence (2 references)
PMID:8701600 SUPPORT Other
"The mechanism of action of HPMPC is based upon the interaction of its active intracellular metabolite, the diphosphorylated HPMPC derivative HPMPCpp, with the viral DNA polymerase."
This review directly supports the polymerase-target mechanism.
PMID:15865216 SUPPORT In Vitro
"Susceptibility to cidofovir was comparable between species with inhibition of replication of all tested serotypes in a narrow dose range (IC50=17-81 microM)."
This in-vitro study directly supports cidofovir inhibition of adenovirus replication.
Show evidence (2 references)
PMID:30859626 SUPPORT Other
"The use of antiviral therapy is not supported by prospective randomized clinical trials. However, intravenous cidofovir is considered the standard practice for treatment of severe, progressive, or disseminated adenovirus disease in most transplant centers."
Transplant guidance supports only the selected severe-disease use and explicitly records the lack of prospective randomized trials.
PMID:28114362 SUPPORT Human Clinical
"It would be unsafe to offer cidofovir to all HAdV pneumonia patients because of the risk of renal toxicity."
This clinical outbreak report supports restricting cidofovir rather than treating all cases.
Live Oral Adenovirus Type 4 and 7 Vaccine
Action: vaccinationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is vaccination (NCIT:C15346). NCIT:C15346 is a clinical intervention from the NCI Thesaurus. Ontology label: Vaccination NCIT:C15346
In U.S. military recruits, the live oral type 4/type 7 vaccine directly prevented type-4 febrile acute respiratory disease. Type 7 was not expected to circulate during the trial, so its primary endpoint was neutralizing-antibody seroconversion rather than clinical efficacy. This is a targeted prevention strategy, not treatment of established disease.
Show evidence (2 references)
PMID:23623865 SUPPORT Human Clinical
"Vaccine efficacy was 99.3% (95% CI, 96.0-99.9; P<0.001)."
The phase 3 randomized trial directly quantifies efficacy against the ADV-4 febrile-ARD endpoint in military recruits.
PMID:23623865 SUPPORT Human Clinical
"The primary endpoints were prevention of febrile ARD due to ADV-4 and seroconversion of neutralizing serum antibodies to ADV-7, which was not expected to circulate in the study population during the course of the trial."
The trial design distinguishes direct type-4 clinical efficacy from the type-7 immunogenicity endpoint.
🌍

Environmental Factors

1
Crowded congregate settings
Close contact in crowded settings facilitates outbreaks of respiratory adenovirus, classically among military recruits.
Show evidence (1 reference)
PMID:27486739 SUPPORT Other
"Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits)."
This review directly supports crowded congregate settings as an outbreak context.
🔬

Diagnosis

2
Respiratory-specimen adenovirus PCR
Adenovirus nucleic-acid testing on respiratory specimens detects viral DNA and supports an etiologic diagnosis when interpreted with a compatible syndrome; multiplex respiratory PCR simultaneously assesses clinically overlapping causes.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Detection of adenovirus DNA in a compatible respiratory syndrome supports, but does not by itself establish, active etiologic infection.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"Patient blood and sputum samples were subjected to conventional culture, serology, and polymerase chain reaction tests for respiratory viruses and atypical pathogens."
This clinical outbreak study used respiratory-specimen PCR as part of etiologic diagnosis.
Quantitative PCR and tissue confirmation in severe or immunocompromised disease
In severe or disseminated disease, serial quantitative PCR can help follow viral burden; culture, molecular testing, and tissue sampling are interpreted with the affected-organ syndrome.
diagnostic procedure NCIT:C18020 NCI Thesaurus (NCIT)
Results: Rising or persistent adenovirus DNA with compatible organ disease supports progressive infection.
Show evidence (2 references)
PMID:30859626 SUPPORT Other
"Serial quantitative PCR might play a role in the decision to initiate or assess response to therapy in a symptomatic patient."
Transplant infectious-disease guidance supports serial quantitative PCR in symptomatic patients.
PMID:34856601 SUPPORT Other
"Diagnosis requires astute clinical awareness of the patient's clinical presentation that would be compatible with adenovirus combined with cultures, molecular testing, polymerase chain reaction, and tissue sampling."
This review supports multimodal confirmation in the relevant clinical context.
🦠

Infectious Agent

1
Human mastadenovirus
The human-infecting mastadenoviruses include multiple types with different tissue tropisms. Respiratory disease is especially associated with types in species B, C, and E, although the circulating type distribution varies by place and time.
Human mastadenovirus NCBITaxon:3567875 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:27486739 SUPPORT Other
"More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection."
This review supports a type-diverse human adenovirus agent with type-dependent clinical tropism.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Adenovirus Respiratory Infection:

Influenza MONDO:0005812
Overlapping Features Influenza A/B was included among pathogen-specific viral tests in the etiologic workup of pneumonia during the adenovirus outbreak.
Distinguishing Features
  • Pathogen-specific multiplex PCR distinguishes influenza A/B from adenovirus.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"This assay targets 12 types of pathogenic RNA viruses: rhinoviruses A/B/C, influenza viruses A/B"
The named multiplex panel directly supports influenza A/B as a pathogen tested separately from adenovirus in the pneumonia differential.
Respiratory syncytial virus infection MONDO:0001577
Overlapping Features Respiratory syncytial viruses A/B were included among pathogen-specific viral tests in the etiologic workup of pneumonia during the adenovirus outbreak.
Distinguishing Features
  • Pathogen-specific multiplex PCR distinguishes RSV A/B from adenovirus.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"respiratory syncytial viruses A/B, parainfluenza viruses 1/2/3"
The named multiplex panel directly supports RSV A/B as pathogens tested separately from adenovirus in the pneumonia differential.
Mycoplasma pneumoniae pneumonia MONDO:0005867
Overlapping Features Mycoplasma pneumoniae was detected by PCR in bronchial-washing or bronchoalveolar-lavage specimens during the adenovirus pneumonia workup.
Distinguishing Features
  • Separate pathogen-specific molecular testing distinguishes M. pneumoniae from adenovirus.
Show evidence (1 reference)
PMID:28114362 SUPPORT Human Clinical
"detected HAdV in 5/18 (27.8%) patients and M. pneumoniae in 3/18 (16.7%) patients (Table 2)."
The study directly names M. pneumoniae as a separately detected pathogen in the same etiologic workup, supporting its inclusion in the differential.
📊

Related Datasets

1
RNAseq analysis of blood from respiratory viruses-infected patients and healthy controls geo:GSE157240
The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections high-lighted the importance of interferon pathway activation. However, the magnitude of the re-sponses varied between pathogens.
human BULK RNA SEQ n=187
PMID:34777354
Identified by GEO DataSets index search for Adenovirus Respiratory Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
{ }

Source YAML

click to show 
name: Adenovirus Respiratory Infection
creation_date: "2026-06-28T00:00:00Z"
description: >-
  Adenovirus respiratory infection is an acute infection caused by human
  adenoviruses, non-enveloped double-stranded DNA viruses with type-dependent
  tissue tropism. Most disease in immunocompetent people is mild and
  self-limited, but adenovirus can cause pharyngitis, conjunctivitis, and lower
  respiratory infection. Severe pneumonia occurs particularly in young
  children, crowded congregate settings such as military training, and people
  with impaired immunity; survivors of severe pediatric pneumonia can develop
  chronic respiratory sequelae including bronchiolitis obliterans.
category: Infectious Disease
parents:
- Viral Respiratory Infection
synonyms:
- Human adenovirus respiratory infection
- HAdV respiratory infection
- Adenoviral pneumonia
infectious_agent:
- name: Human mastadenovirus
  infectious_agent_term:
    preferred_term: Human mastadenovirus
    term:
      id: NCBITaxon:3567875
      label: Human mastadenovirus
  description: >-
    The human-infecting mastadenoviruses include multiple types with different
    tissue tropisms. Respiratory disease is especially associated with types in
    species B, C, and E, although the circulating type distribution varies by
    place and time.
  evidence:
  - reference: PMID:27486739
    reference_title: "Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      More than 50 serotypes of AdV have been identified. Different serotypes
      display different tissue tropisms that correlate with clinical manifestations
      of infection.
    explanation: >-
      This review supports a type-diverse human adenovirus agent with
      type-dependent clinical tropism.
pathophysiology:
- name: Adenoviral DNA Polymerase Activity
  role: therapeutic_vulnerability
  biological_scale: MOLECULAR
  conforms_to: "viral_polymerase_inhibition#Nucleotide Selection and Catalytic Incorporation at the Polymerase Active Site"
  description: >-
    Adenoviral DNA polymerase copies the double-stranded DNA genome. The active
    diphosphorylated metabolite of cidofovir interacts with viral DNA polymerase,
    making this replication step a pharmacologic vulnerability, although
    clinical evidence for cidofovir in adenovirus disease remains limited.
  biological_processes:
  - preferred_term: viral genome replication
    term:
      id: GO:0019079
      label: viral genome replication
  molecular_functions:
  - preferred_term: nucleotidyltransferase activity
    term:
      id: GO:0016779
      label: nucleotidyltransferase activity
  evidence:
  - reference: PMID:8701600
    reference_title: "Therapeutic potential of Cidofovir (HPMPC, Vistide) for the treatment of DNA virus (i.e. herpes-, papova-, pox- and adenovirus) infections."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The mechanism of action of HPMPC is based upon the interaction of its active
      intracellular metabolite, the diphosphorylated HPMPC derivative HPMPCpp, with
      the viral DNA polymerase.
    explanation: >-
      This review directly identifies viral DNA polymerase as the molecular target
      of active cidofovir metabolite.
  downstream:
  - target: Respiratory Epithelial Infection and Viral Replication
    description: >-
      Viral DNA synthesis supports productive replication in infected respiratory
      epithelial cells.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:15865216
      reference_title: "In vitro susceptibility of adenovirus to antiviral drugs is species-dependent."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Susceptibility to cidofovir was comparable between species with inhibition
        of replication of all tested serotypes in a narrow dose range (IC50=17-81 microM).
      explanation: >-
        Pharmacologic inhibition across tested adenovirus serotypes supports the
        dependence of productive viral replication on this cidofovir-sensitive step.
- name: Respiratory Epithelial Infection and Viral Replication
  role: trigger
  biological_scale: CELLULAR
  description: >-
    Human adenovirus infects respiratory epithelial cells and replicates its DNA
    genome. Respiratory infection is usually mild and self-limited in
    immunocompetent hosts, but type and host context influence whether disease
    remains localized or progresses to pneumonia.
  cell_types:
  - preferred_term: respiratory epithelial cell
    term:
      id: CL:0002632
      label: epithelial cell of lower respiratory tract
  - preferred_term: ciliated airway epithelial cell
    term:
      id: CL:0002145
      label: multiciliated columnar cell of tracheobronchial tree
  biological_processes:
  - preferred_term: viral genome replication
    term:
      id: GO:0019079
      label: viral genome replication
  locations:
  - preferred_term: respiratory system
    term:
      id: UBERON:0001004
      label: respiratory system
  evidence:
  - reference: PMID:27486739
    reference_title: "Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Adenoviruses (AdVs) are DNA viruses that typically cause mild infections
      involving the upper or lower respiratory tract, gastrointestinal tract, or
      conjunctiva.
    explanation: >-
      This review establishes adenovirus infection of upper and lower respiratory
      sites and its usually mild clinical course.
  - reference: PMID:33072092
    reference_title: "Adenovirus 7 Induces Interlukin-6 Expression in Human Airway Epithelial Cells via p38/NF-κB Signaling Pathway."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      AdV 7 infection of bronchial epithelial cell line and primary airway
      epithelial cells confirmed that AdV 7 increased IL-6 mRNA and protein
      expression in an infection dose-dependent manner.
    explanation: >-
      Infection experiments directly establish adenovirus type 7 infection of
      bronchial and primary airway epithelial cells.
  downstream:
  - target: Innate Antiviral Response
    description: >-
      Entry and genome replication expose viral components to cellular innate
      recognition pathways, including DNA sensors that trigger interferon.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:24512150
      reference_title: Innate immunity to adenovirus.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Here we describe how adenoviruses are recognized by the host innate defense
        system during entry and replication in immune and nonimmune cells.
      explanation: >-
        The review directly links adenovirus entry and replication to host innate
        recognition.
  - target: Airway Pro-inflammatory Cytokine Response
    description: >-
      Adenovirus type 7 infection activates p38/NF-kappaB signaling in airway
      epithelial cells and increases airway inflammatory cytokines.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:33072092
      reference_title: "Adenovirus 7 Induces Interlukin-6 Expression in Human Airway Epithelial Cells via p38/NF-κB Signaling Pathway."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Signaling pathway analysis revealed that p38/NF-κB pathway was involved in
        AdV 7 infection induced IL-6 elevation.
      explanation: >-
        Airway-cell perturbation experiments directly support p38/NF-kappaB-driven
        IL-6 induction after adenovirus type 7 infection.
  - target: Conjunctivitis
    description: >-
      Human adenovirus mucosal tropism includes conjunctival infection; the
      cited spectrum evidence does not establish co-occurrence with the
      respiratory syndrome in the same patients.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:27486739
      reference_title: "Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Adenoviruses (AdVs) are DNA viruses that typically cause mild infections
        involving the upper or lower respiratory tract, gastrointestinal tract, or
        conjunctiva.
      explanation: >-
        The review establishes conjunctival involvement in the adenovirus disease
        spectrum, but it does not resolve the causal intermediates from respiratory
        epithelial infection to conjunctivitis.
- name: Innate Antiviral Response
  biological_scale: CELLULAR
  conforms_to: "innate_antiviral_interferon_response#Interferon-Stimulated Gene Antiviral State"
  description: >-
    Intrinsic restriction factors, pattern-recognition receptors, and cytosolic
    DNA sensors mount an antiviral response to adenovirus and trigger interferon.
    Adenovirus early proteins and virus-associated RNAs counter several of these
    defenses, so the net response varies by cell and host context.
  biological_processes:
  - preferred_term: antiviral innate immune response
    term:
      id: GO:0140374
      label: antiviral innate immune response
  - preferred_term: defense response to virus
    term:
      id: GO:0051607
      label: defense response to virus
  evidence:
  - reference: PMID:24512150
    reference_title: Innate immunity to adenovirus.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Important innate factors restricting adenovirus in the cytosol are tripartite
      motif-containing proteins, nucleotide-binding oligomerization domain-like
      inflammatory receptors, and DNA sensors triggering interferon, such as DEAD
      (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine
      monophosphate-adenosine monophosphate synthase.
    explanation: >-
      This review supports cytosolic restriction and DNA-sensor-driven interferon
      responses to adenovirus.
  downstream: []
- name: Airway Pro-inflammatory Cytokine Response
  biological_scale: CELLULAR
  description: >-
    In airway samples from children with adenovirus type 7 infection, multiple
    inflammatory cytokines are elevated. In airway epithelial models, infection
    activates p38/NF-kappaB signaling and IL-6 expression; excessive inflammation
    is a plausible contributor to tissue injury and severe symptoms.
  cell_types:
  - preferred_term: respiratory epithelial cell
    term:
      id: CL:0002632
      label: epithelial cell of lower respiratory tract
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  locations:
  - preferred_term: respiratory system
    term:
      id: UBERON:0001004
      label: respiratory system
  evidence:
  - reference: PMID:33072092
    reference_title: "Adenovirus 7 Induces Interlukin-6 Expression in Human Airway Epithelial Cells via p38/NF-κB Signaling Pathway."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our results showed that eight out of 13 tested inflammatory cytokines were
      significantly increased in nasal washes of AdV 7-infected children comparing
      to healthy control, with IL-6 showing the highest enhancement.
    explanation: >-
      Patient airway samples directly support a broad pro-inflammatory response in
      adenovirus type 7 infection.
  downstream:
  - target: Upper Respiratory Clinical Syndrome
    description: >-
      Airway infection and inflammation manifest clinically with prolonged fever,
      nasal congestion, sore throat, and pharyngeal inflammation.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:28114362
      reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        High and prolonged fever, nasal congestion, sore throat, and pharyngeal
        inflammation were significantly more common in the HAdV pneumonia group,
        compared to patients with other or unknown causes of pneumonia.
      explanation: >-
        This prospective outbreak cohort associates laboratory-confirmed adenovirus
        pneumonia with the upper-airway syndrome, but it does not isolate the
        cytokine response as the causal mediator.
  - target: Cough
    description: >-
      Airway inflammation during pediatric adenovirus pneumonia commonly produces
      cough.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:34712627
      reference_title: Analysis of Clinical Characteristics and Risk Factors of Severe Adenovirus Pneumonia in Children.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        All patients had cough, and 116 (92.8%) patients with mild cases and 82
        (95.4%) patients with severe cases had varying degrees of fever.
      explanation: >-
        Cough was present throughout this hospitalized pediatric adenovirus
        pneumonia cohort, but the observation does not establish airway cytokines
        as its specific cause.
  - target: Severe Adenovirus Pneumonia and Lung Injury
    description: >-
      Direct viral injury and an excessive inflammatory response can converge on
      severe lower-respiratory disease, although the determinants of progression
      are incompletely resolved.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:37476615
      reference_title: "Pediatric adenovirus pneumonia: clinical practice and current treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        As for pathogenesis, adenoviruses can directly damage target cells and
        activate the immune response to varying degrees.
      explanation: >-
        The review supports direct cell damage and immune activation as components
        of pediatric adenovirus pneumonia but does not establish a single complete
        causal route to severe disease.
- name: Upper Respiratory Clinical Syndrome
  biological_scale: ORGANISM
  description: >-
    Respiratory adenovirus infection often produces a febrile pharyngitis syndrome
    with nasal congestion; the phenotype combination can resemble other viral
    respiratory infections.
  locations:
  - preferred_term: respiratory system
    term:
      id: UBERON:0001004
      label: respiratory system
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      High and prolonged fever, nasal congestion, sore throat, and pharyngeal
      inflammation were significantly more common in the HAdV pneumonia group,
      compared to patients with other or unknown causes of pneumonia.
    explanation: >-
      The outbreak cohort supports the defining febrile upper-airway symptom
      cluster.
  downstream:
  - target: Fever
    description: Confirmed respiratory adenovirus infection is associated with high, often prolonged fever.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:28114362
      reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        High and prolonged fever, nasal congestion, sore throat, and pharyngeal
        inflammation were significantly more common in the HAdV pneumonia group,
        compared to patients with other or unknown causes of pneumonia.
      explanation: >-
        The cohort supports fever as a component of the syndrome but does not
        establish a separate mechanistic causal route from the syndrome node.
  - target: Pharyngitis
    description: Sore throat and pharyngeal inflammation constitute adenoviral pharyngitis.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:28114362
      reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        High and prolonged fever, nasal congestion, sore throat, and pharyngeal
        inflammation were significantly more common in the HAdV pneumonia group,
        compared to patients with other or unknown causes of pneumonia.
      explanation: >-
        The cohort supports pharyngeal inflammation as a component of the syndrome
        but does not establish a separate mechanistic causal route from the syndrome
        node.
  - target: Nasal Congestion
    description: Nasal congestion accompanies the febrile respiratory syndrome.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:28114362
      reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        High and prolonged fever, nasal congestion, sore throat, and pharyngeal
        inflammation were significantly more common in the HAdV pneumonia group,
        compared to patients with other or unknown causes of pneumonia.
      explanation: >-
        The cohort supports nasal congestion as a component of the syndrome but
        does not establish a separate mechanistic causal route from the syndrome
        node.
- name: Severe Adenovirus Pneumonia and Lung Injury
  role: consequence
  biological_scale: TISSUE
  description: >-
    A minority of respiratory infections progress to severe lower-respiratory
    disease with extensive inflammatory lung injury. Severe pediatric pneumonia
    can require ventilatory support and may be followed by chronic small-airway
    obstruction, especially bronchiolitis obliterans.
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:30321228
    reference_title: Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      One in five children admitted with HAdV pneumonia had severe disease and 22%
      developed respiratory complications.
    explanation: >-
      This hospitalized pediatric cohort quantifies severe disease and later
      respiratory complications.
  downstream:
  - target: Pneumonia
    description: Lower-respiratory adenovirus infection produces clinically confirmed viral pneumonia.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:28114362
      reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: HAdV pneumonia infected recruit trainees most frequently.
      explanation: >-
        Laboratory etiologic testing identifies adenovirus pneumonia, but this
        occurrence evidence does not independently establish the causal transition
        from the severe-lung-injury node.
  - target: Dyspnea
    description: Severe pediatric adenovirus pneumonia can present with dyspnea and systemic toxicity.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:37476615
      reference_title: "Pediatric adenovirus pneumonia: clinical practice and current treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Early clinical recognition depends on patients' symptoms and laboratory
        tests, including those under 2 years old, dyspnea with systemic toxic symptoms,
        atelectasis or emphysema in CT image, decreased leukocytes, and significantly
        increased C-reaction protein (CRP) and procalcitonin (PCT), indicating the
        possibility of severe cases.
      explanation: >-
        The pediatric review identifies dyspnea as an indicator of severe disease,
        but it does not establish the specific causal mechanism producing dyspnea.
  - target: Respiratory Failure
    description: A subset of adenovirus pneumonia progresses to respiratory failure.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:28114362
      reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        HAdV pneumonia exhibited specific laboratory and clinical features, and
        although most patients were cured without complication, some progressed to
        respiratory failure and fatality.
      explanation: The prospective outbreak cohort documents progression to respiratory failure.
  - target: Bronchiolitis Obliterans
    description: Severe childhood adenovirus pneumonia can be followed by chronic obliterative small-airway disease.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:30321228
      reference_title: Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Twenty-two percent developed respiratory complications, the commonest being
        bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%).
      explanation: >-
        This follow-up cohort establishes bronchiolitis obliterans as a post-pneumonia
        sequela, but observational follow-up does not by itself establish the full
        causal mechanism.
phenotypes:
- category: Respiratory
  name: Pneumonia
  description: Lower-respiratory infection can produce adenoviral pneumonia.
  phenotype_term:
    preferred_term: Pneumonia
    term:
      id: HP:0002090
      label: Pneumonia
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: HAdV pneumonia infected recruit trainees most frequently.
    explanation: Etiologic testing documented an adenovirus pneumonia outbreak.
- category: Constitutional
  name: Fever
  description: Fever can be high and prolonged in adenovirus pneumonia.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      High and prolonged fever, nasal congestion, sore throat, and pharyngeal
      inflammation were significantly more common in the HAdV pneumonia group,
      compared to patients with other or unknown causes of pneumonia.
    explanation: The prospective outbreak cohort directly supports fever.
- category: Respiratory
  name: Pharyngitis
  description: Sore throat and pharyngeal inflammation are characteristic upper-airway manifestations.
  phenotype_term:
    preferred_term: Pharyngitis
    term:
      id: HP:0025439
      label: Pharyngitis
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      High and prolonged fever, nasal congestion, sore throat, and pharyngeal
      inflammation were significantly more common in the HAdV pneumonia group,
      compared to patients with other or unknown causes of pneumonia.
    explanation: The prospective outbreak cohort directly supports pharyngeal inflammation.
- category: Respiratory
  name: Nasal Congestion
  description: Nasal congestion accompanies adenovirus respiratory illness.
  phenotype_term:
    preferred_term: Nasal congestion
    term:
      id: HP:0001742
      label: Nasal congestion
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      High and prolonged fever, nasal congestion, sore throat, and pharyngeal
      inflammation were significantly more common in the HAdV pneumonia group,
      compared to patients with other or unknown causes of pneumonia.
    explanation: The prospective outbreak cohort directly supports nasal congestion.
- category: Ophthalmologic
  name: Conjunctivitis
  description: >-
    Conjunctival infection is part of the human adenovirus disease spectrum;
    co-occurrence with respiratory disease is not asserted from this source.
  phenotype_term:
    preferred_term: Conjunctivitis
    term:
      id: HP:0000509
      label: Conjunctivitis
  evidence:
  - reference: PMID:27486739
    reference_title: "Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Adenoviruses (AdVs) are DNA viruses that typically cause mild infections
      involving the upper or lower respiratory tract, gastrointestinal tract, or
      conjunctiva.
    explanation: This review directly supports conjunctival involvement.
- category: Respiratory
  name: Cough
  description: Cough is a common manifestation of adenovirus pneumonia.
  phenotype_term:
    preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: PMID:34712627
    reference_title: Analysis of Clinical Characteristics and Risk Factors of Severe Adenovirus Pneumonia in Children.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All patients had cough, and 116 (92.8%) patients with mild cases and 82
      (95.4%) patients with severe cases had varying degrees of fever.
    explanation: Cough was present in all children in this hospitalized pneumonia cohort.
- category: Respiratory
  name: Dyspnea
  description: Dyspnea is a warning feature of severe pediatric adenovirus pneumonia.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:37476615
    reference_title: "Pediatric adenovirus pneumonia: clinical practice and current treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Early clinical recognition depends on patients' symptoms and laboratory
      tests, including those under 2 years old, dyspnea with systemic toxic symptoms,
      atelectasis or emphysema in CT image, decreased leukocytes, and significantly
      increased C-reaction protein (CRP) and procalcitonin (PCT), indicating the
      possibility of severe cases.
    explanation: This review identifies dyspnea as an indicator of severe disease.
- category: Respiratory
  name: Respiratory Failure
  description: Severe adenovirus pneumonia can progress to respiratory failure.
  phenotype_term:
    preferred_term: Respiratory failure
    term:
      id: HP:0002878
      label: Respiratory failure
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      HAdV pneumonia exhibited specific laboratory and clinical features, and
      although most patients were cured without complication, some progressed to
      respiratory failure and fatality.
    explanation: The prospective outbreak cohort documents respiratory failure.
- category: Respiratory
  name: Bronchiolitis Obliterans
  description: Chronic obliterative small-airway disease can follow severe childhood adenovirus pneumonia.
  phenotype_term:
    preferred_term: Bronchiolitis obliterans
    term:
      id: HP:0011946
      label: Bronchiolitis obliterans
    temporality: CHRONIC
  evidence:
  - reference: PMID:30321228
    reference_title: Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Twenty-two percent developed respiratory complications, the commonest being
      bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%).
    explanation: This follow-up cohort directly supports bronchiolitis obliterans as a sequela.
environmental:
- name: Crowded congregate settings
  description: >-
    Close contact in crowded settings facilitates outbreaks of respiratory
    adenovirus, classically among military recruits.
  effect: Increases exposure and outbreak risk.
  evidence:
  - reference: PMID:27486739
    reference_title: "Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Epidemics of AdV infection may occur in healthy children or adults in closed
      or crowded settings (particularly military recruits).
    explanation: This review directly supports crowded congregate settings as an outbreak context.
diagnosis:
- name: Respiratory-specimen adenovirus PCR
  description: >-
    Adenovirus nucleic-acid testing on respiratory specimens detects viral DNA
    and supports an etiologic diagnosis when interpreted with a compatible
    syndrome; multiplex respiratory PCR simultaneously assesses clinically
    overlapping causes.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  results: >-
    Detection of adenovirus DNA in a compatible respiratory syndrome supports,
    but does not by itself establish, active etiologic infection.
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patient blood and sputum samples were subjected to conventional culture,
      serology, and polymerase chain reaction tests for respiratory viruses and
      atypical pathogens.
    explanation: This clinical outbreak study used respiratory-specimen PCR as part of etiologic diagnosis.
- name: Quantitative PCR and tissue confirmation in severe or immunocompromised disease
  description: >-
    In severe or disseminated disease, serial quantitative PCR can help follow
    viral burden; culture, molecular testing, and tissue sampling are interpreted
    with the affected-organ syndrome.
  diagnosis_term:
    preferred_term: diagnostic procedure
    term:
      id: NCIT:C18020
      label: Diagnostic Procedure
  results: Rising or persistent adenovirus DNA with compatible organ disease supports progressive infection.
  evidence:
  - reference: PMID:30859626
    reference_title: "Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Serial quantitative PCR might play a role in the decision to initiate or
      assess response to therapy in a symptomatic patient.
    explanation: Transplant infectious-disease guidance supports serial quantitative PCR in symptomatic patients.
  - reference: PMID:34856601
    reference_title: Adenovirus Infection and Transplantation.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Diagnosis requires astute clinical awareness of the patient's clinical
      presentation that would be compatible with adenovirus combined with cultures,
      molecular testing, polymerase chain reaction, and tissue sampling.
    explanation: This review supports multimodal confirmation in the relevant clinical context.
differential_diagnoses:
- name: Influenza
  description: >-
    Influenza A/B was included among pathogen-specific viral tests in the etiologic
    workup of pneumonia during the adenovirus outbreak.
  disease_term:
    preferred_term: influenza
    term:
      id: MONDO:0005812
      label: influenza
  distinguishing_features:
  - Pathogen-specific multiplex PCR distinguishes influenza A/B from adenovirus.
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This assay targets 12 types of pathogenic RNA viruses: rhinoviruses A/B/C,
      influenza viruses A/B
    explanation: >-
      The named multiplex panel directly supports influenza A/B as a pathogen tested
      separately from adenovirus in the pneumonia differential.
- name: Respiratory syncytial virus infection
  description: >-
    Respiratory syncytial viruses A/B were included among pathogen-specific viral
    tests in the etiologic workup of pneumonia during the adenovirus outbreak.
  disease_term:
    preferred_term: respiratory syncytial virus infection
    term:
      id: MONDO:0001577
      label: respiratory syncytial virus infectious disease
  distinguishing_features:
  - Pathogen-specific multiplex PCR distinguishes RSV A/B from adenovirus.
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      respiratory syncytial viruses A/B, parainfluenza viruses 1/2/3
    explanation: >-
      The named multiplex panel directly supports RSV A/B as pathogens tested
      separately from adenovirus in the pneumonia differential.
- name: Mycoplasma pneumoniae pneumonia
  description: >-
    Mycoplasma pneumoniae was detected by PCR in bronchial-washing or
    bronchoalveolar-lavage specimens during the adenovirus pneumonia workup.
  disease_term:
    preferred_term: Mycoplasma pneumoniae pneumonia
    term:
      id: MONDO:0005867
      label: Mycoplasma pneumoniae pneumonia
  distinguishing_features:
  - Separate pathogen-specific molecular testing distinguishes M. pneumoniae from adenovirus.
  evidence:
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      detected HAdV in 5/18 (27.8%) patients and M. pneumoniae in 3/18 (16.7%)
      patients (Table 2).
    explanation: >-
      The study directly names M. pneumoniae as a separately detected pathogen in
      the same etiologic workup, supporting its inclusion in the differential.
treatments:
- name: Supportive and Respiratory Care
  description: >-
    Most respiratory adenovirus infections are self-limited. Severe pneumonia may
    require supplemental oxygen, ventilatory support, and other organ support; no
    adenovirus-specific drug is approved.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:37476615
    reference_title: "Pediatric adenovirus pneumonia: clinical practice and current treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Until now, there is no specific drug for adenovirus pneumonia, so in clinical
      practice, current treatment comprises antiviral drugs, respiratory support and
      bronchoscopy, immunomodulatory therapy, and blood purification.
    explanation: The pediatric review supports respiratory and organ-supportive management in severe disease.
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Most patients in our study were treated empirically with antibiotics, and most
      HAdV pneumonia cases were self-limiting without an antiviral agent.
    explanation: This outbreak cohort supports the self-limited course in most immunocompetent patients.
- name: Intravenous Cidofovir for Selected Severe Disease
  description: >-
    Intravenous cidofovir is used off label in some transplant centers for severe,
    progressive, or disseminated adenovirus disease. This is not an approved
    general treatment for uncomplicated respiratory infection, prospective
    randomized efficacy data are absent, and nephrotoxicity limits use.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: cidofovir
      term:
        id: NCIT:C1600
        label: Cidofovir
  target_mechanisms:
  - target: Adenoviral DNA Polymerase Activity
    treatment_effect: INHIBITS
    description: >-
      Intracellular cidofovir diphosphate interacts with viral DNA polymerase, and
      cidofovir inhibits replication across tested adenovirus serotypes in vitro.
    evidence:
    - reference: PMID:8701600
      reference_title: "Therapeutic potential of Cidofovir (HPMPC, Vistide) for the treatment of DNA virus (i.e. herpes-, papova-, pox- and adenovirus) infections."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        The mechanism of action of HPMPC is based upon the interaction of its active
        intracellular metabolite, the diphosphorylated HPMPC derivative HPMPCpp, with
        the viral DNA polymerase.
      explanation: This review directly supports the polymerase-target mechanism.
    - reference: PMID:15865216
      reference_title: "In vitro susceptibility of adenovirus to antiviral drugs is species-dependent."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Susceptibility to cidofovir was comparable between species with inhibition
        of replication of all tested serotypes in a narrow dose range (IC50=17-81 microM).
      explanation: This in-vitro study directly supports cidofovir inhibition of adenovirus replication.
  evidence:
  - reference: PMID:30859626
    reference_title: "Adenovirus in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The use of antiviral therapy is not supported by prospective randomized clinical
      trials. However, intravenous cidofovir is considered the standard practice for
      treatment of severe, progressive, or disseminated adenovirus disease in most
      transplant centers.
    explanation: >-
      Transplant guidance supports only the selected severe-disease use and explicitly
      records the lack of prospective randomized trials.
  - reference: PMID:28114362
    reference_title: Clinical Features and Courses of Adenovirus Pneumonia in Healthy Young Adults during an Outbreak among Korean Military Personnel.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It would be unsafe to offer cidofovir to all HAdV pneumonia patients because of
      the risk of renal toxicity.
    explanation: This clinical outbreak report supports restricting cidofovir rather than treating all cases.
- name: Live Oral Adenovirus Type 4 and 7 Vaccine
  description: >-
    In U.S. military recruits, the live oral type 4/type 7 vaccine directly
    prevented type-4 febrile acute respiratory disease. Type 7 was not expected
    to circulate during the trial, so its primary endpoint was neutralizing-antibody
    seroconversion rather than clinical efficacy. This is a targeted
    prevention strategy, not treatment of established disease.
  therapeutic_modality: VACCINE
  treatment_term:
    preferred_term: vaccination
    term:
      id: NCIT:C15346
      label: Vaccination
  evidence:
  - reference: PMID:23623865
    reference_title: "A phase 3, randomized, double-blind, placebo-controlled study of the safety and efficacy of the live, oral adenovirus type 4 and type 7 vaccine, in U.S. military recruits."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vaccine efficacy was 99.3% (95% CI, 96.0-99.9; P<0.001).
    explanation: >-
      The phase 3 randomized trial directly quantifies efficacy against the
      ADV-4 febrile-ARD endpoint in military recruits.
  - reference: PMID:23623865
    reference_title: "A phase 3, randomized, double-blind, placebo-controlled study of the safety and efficacy of the live, oral adenovirus type 4 and type 7 vaccine, in U.S. military recruits."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The primary endpoints were prevention of febrile ARD due to ADV-4 and
      seroconversion of neutralizing serum antibodies to ADV-7, which was not
      expected to circulate in the study population during the course of the
      trial.
    explanation: >-
      The trial design distinguishes direct type-4 clinical efficacy from the
      type-7 immunogenicity endpoint.
notes: >-
  This entry is deliberately restricted to respiratory adenovirus disease. No
  exact respiratory-adenovirus MONDO term is currently available; the broader
  MONDO:0043479 (adenoviridae infectious disease) is not used as a disease_term
  because it does not preserve this entry's narrower scope. The generic NCBITaxon human
  mastadenovirus term is used because multiple human adenovirus types cause
  respiratory disease. Cidofovir is represented as selected off-label therapy,
  not routine treatment, and conjunctivitis is retained only as the recognized
  conjunctival-infection branch without asserting respiratory co-occurrence.
datasets:
- accession: geo:GSE157240
  title: RNAseq analysis of blood from respiratory viruses-infected patients and healthy controls
  description: The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections high-lighted the importance of interferon pathway activation. However, the magnitude of the re-sponses varied between pathogens.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 187
  publication: PMID:34777354
  notes: Identified by GEO DataSets index search for Adenovirus Respiratory Infection (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.