Respiratory involvement:

Acute pharyngoconjunctival fever

High fever, sore throat, cervical lymphadenopathy

Painful red eyes, watery discharge, photophobia

Cough, hoarseness, chest discomfort

Lower respiratory tract disease:

Bronchiolitis or pneumonia

Tachypnea, wheeze, crepitations

Hypoxia in severe cases

May mimic bacterial pneumonia

Gastrointestinal involvement:

Diarrhea, vomiting, abdominal cramps

Non-bloody diarrhea common in young children

May be associated with mesenteric adenitis mimicking appendicitis

Ocular involvement:

Conjunctivitis (follicular)

Preauricular lymphadenopathy

Keratoconjunctivitis with photophobia, blurred vision

Genitourinary involvement:

Hemorrhagic cystitis

Dysuria, frequency, suprapubic discomfort

Gross hematuria in children (usually self-limiting)

Systemic involvement:

Arthralgias, myalgias, malaise

Occasional hepatitis or rash

Multiorgan involvement in immunocompromised patients

Course:

Usually self-limited

Symptoms resolve in 5–10 days except keratitis, which may persist for weeks

Bronchiolitis

Otitis media

Sinusitis

Chronic keratitis (rare)

Severe dehydration from diarrhea/vomiting

Cardiac:

Myocarditis

Pericarditis (rare)

Genitourinary:

Hemorrhagic cystitis (especially serotypes 11, 21)

Nephritis (rare)

Multisystem / severe disease:

Disseminated adenovirus infection in immunocompromised patients

Organ failure (lung, liver, GI) in transplant or oncology patients

Post-infectious:

Reactive airway disease / recurrent wheeze in children after severe adenoviral pneumonia

Viral respiratory illnesses:

Influenza (typically higher fever, abrupt onset)

RSV (more wheeze, bronchiolitis in infants)

Parainfluenza (croup more common)

Rhinovirus (milder symptoms)

COVID-19 (anosmia, broader systemic features)

Bacterial infections:

Streptococcal pharyngitis (more exudates, tender lymph nodes, positive rapid strep test)

Mycoplasma pneumoniae (dry cough, extrapulmonary symptoms)

Pertussis (paroxysmal cough)

Conjunctival disease:

Allergic conjunctivitis (itching dominant, bilateral watery eyes)

Bacterial conjunctivitis (purulent discharge)

Herpes simplex keratitis (dendritic lesions on fluorescein)

Gastrointestinal:

Rotavirus (profuse watery diarrhea in infants)

Norovirus (vomiting prominent, short duration)

Bacterial gastroenteritis (bloody stools, high fever)

Genitourinary:

UTI (positive nitrites/leukocyte esterase; bacterial culture positive)

BK virus hemorrhagic cystitis in immunocompromised patients

Others:

Measles (cough, coryza, Koplik spots; generalized rash)

Kawasaki disease (persistent fever, mucocutaneous changes)

More than 100 serotypes exist, but around 50 infect humans; different serotypes have tropism for different organs.

Transmission routes:

– Respiratory droplets

– Fecal–oral spread

– Contaminated water (swimming pools)

– Eye-to-eye contamination (fomites, towels, instruments)

– Close person-to-person contact

Latency:

Adenovirus can remain latent in adenoids and tonsils and reactivate in immunosuppression.

Basic tests:

CBC may show normal or mild leukocytosis

CRP/ESR mildly elevated in viral presentations

Procalcitonin usually low (helps distinguish from bacterial pneumonia)

Respiratory diagnostics:

Nasopharyngeal swab → PCR for adenovirus (gold standard)

Rapid antigen testing available but less sensitive

Viral culture possible but slow and rarely needed

Ocular disease:

Conjunctival swab PCR confirms epidemic keratoconjunctivitis

Fluorescein staining → punctate epithelial keratitis

Gastrointestinal disease:

Stool PCR detects enteric adenovirus serotypes 40/41

Stool antigen tests can also be used in children with diarrhea

Electrolytes to assess dehydration

Hemorrhagic cystitis:

Urine analysis → hematuria, mild proteinuria

Urine PCR for adenovirus in severe cases

Pneumonia:

Chest X-ray may show patchy infiltrates, perihilar opacities, or hyperinflation

Consider CT chest only in complicated or non-resolving cases

Immunocompromised patients:

Quantitative adenovirus PCR (blood) for viral load monitoring

Liver/renal function tests if systemic involvement suspected

Adenovirus infects mucosal epithelial cells throughout the airway—from nasopharynx to bronchioles—so disease ranges from pharyngitis to pneumonia.

It causes dense consolidation, high fever, and leukocytosis in some serotypes, especially type 7—appearing similar to bacterial infection.

Severe adenoviral injury to small airways triggers chronic inflammation → fibrosis → fixed airflow obstruction.

Crowding + stress + close contact + certain adenovirus serotypes (4 & 7) spread efficiently in dormitory settings.

They are non-enveloped, making them resistant to drying, detergents, and disinfectants—enhancing fomite transmission.

Virus replicates in ocular epithelium → inflammation → watery discharge and irritation; very contagious.

Enteric adenovirus types 40 & 41 replicate in intestinal mucosa, especially in young children.

There are many adenovirus serotypes; immunity is serotype-specific, so infection with one type does not protect against others.

T-cell–mediated immunity is required to control adenovirus; immunosuppressed patients cannot clear the virus effectively.

Some serotypes cause intense conjunctival inflammation due to direct epithelial cytotoxicity.

In immunocompromised hosts, reactivation or uncontrolled replication can lead to severe disseminated disease.

Replication occurs in epithelial cells of respiratory tract, conjunctiva, gastrointestinal mucosa, and urinary tract.

*Intranuclear smudge cells are characteristic of adenovirus infection.* These are epithelial cells with dense basophilic inclusions.

Lytic destruction of respiratory epithelium leads to mucosal erosion, inflammation, and obstruction of bronchioles especially in infants.

Lymphoid hyperplasia may occur in tonsils, adenoids, and Peyer's patches.

Hemorrhagic cystitis shows mucosal edema, submucosal hemorrhage, and viral cytopathic changes in the urothelium.

Immunocompromised patients may develop disseminated necrotizing infection affecting liver, heart, brain, and multiple organs.

Only certain military vaccines (live oral serotypes 4 & 7) exist; not used in civilians.

Hygiene & transmission reduction:

Frequent handwashing with soap and water

Avoid touching eyes, nose, mouth with unwashed hands

Use alcohol-based sanitizers if soap unavailable

Disinfect commonly touched surfaces (doorknobs, railings, toys)

Prevention of respiratory spread:

Cover coughs & sneezes with tissue or elbow

Avoid close contact with infected individuals

Keep children home until fever subsides

Improve ventilation in crowded places

Prevention of ocular infection:

Avoid sharing towels, pillows, cosmetics, eye makeup

Discard contaminated contact lenses

Ensure proper contact lens hygiene (cleaning & storage)

Swimming pool–associated outbreaks:

Ensure adequate chlorination of pools

Shower before swimming

Exclude individuals with active conjunctivitis

Hospital infection control:

Contact + droplet precautions

Use dedicated medical equipment when possible

Strict hand hygiene between patients

Isolation for severe or immunocompromised cases

For immunocompromised patients:

Routine surveillance PCR in transplant settings

Minimize unnecessary immunosuppression

Early treatment if high viral load is detected

Adequate sleep, balanced diet, hydration, sunlight exposure, and physical activity.

Chest radiograph may be normal in mild infection.

*Perihilar streaky opacities* are common due to bronchiolitis and peribronchial inflammation.

Patchy bilateral infiltrates can appear, often mimicking bacterial pneumonia.

Hyperinflation may be present in infants because of small airway obstruction.

Adenovirus pneumonia can show *lobar consolidation*, especially in severe cases, sometimes indistinguishable from bacterial pneumonia.

Adenovirus serotype 7 is associated with more severe lung involvement including diffuse alveolar damage.

CT chest may show peribronchial thickening, ground-glass opacities, and focal areas of consolidation.

Chronic adenovirus infection in children can lead to *bronchiolitis obliterans* with mosaic attenuation and air-trapping on CT scans.

There are > 50 human adenovirus serotypes, grouped into seven species:

Adenovirus species A

Adenovirus species B

Adenovirus species C

Adenovirus species D

Adenovirus species E

Adenovirus species F

Adenovirus species G

Common disease-associated serotypes:

Respiratory illness:

Serotype 1, 2, 3, 4, 5, 7, 14, 21

Pharyngoconjunctival fever (PCF):

Serotype 3, 4, 7

Epidemic keratoconjunctivitis (EKC):

Serotype 8, 19, 37

Gastroenteritis:

Serotype 40, 41 (enteric adenoviruses)

Hemorrhagic cystitis:

Serotype 11, 21

Hepatitis (rare, immunocompromised):

Serotype 5, 7

Species F (Ad40, Ad41):

Strongly enteric, resistant to gastric acid → diarrhea in infants

Species B (Ad3, 7, 11, 14, 21):

Associated with severe respiratory outbreaks & hemorrhagic cystitis

Species D:

Major cause of ocular disease (EKC)

Preauricular lymph node enlargement in conjunctivitis

Tachypnea or increased work of breathing (nasal flaring, intercostal retractions) in lower respiratory involvement

Signs of dehydration (sunken eyes, dry mucosa) in gastroenteritis

Abdominal tenderness or hyperactive bowel sounds (enteric serotypes)

Costovertebral angle discomfort or suprapubic tenderness in hemorrhagic cystitis

Hepatosplenomegaly is rare but may be seen in systemic involvement

Rash may be present in exanthem forms

Transmission is via respiratory droplets, fecal–oral contact, fomites, and contaminated water (including swimming pools).

Illness is generally mild in healthy individuals but can be severe or disseminated in neonates, transplant patients, and immunocompromised hosts.

Outbreaks occur in schools, military recruits, day-care centers, and swimming pools.

Otitis media in children

Hoarseness or laryngitis may occur in upper respiratory involvement

Hemorrhagic cystitis: dysuria, frequency, hematuria (mainly serotypes 11, 21)

Shortness of breath or wheezing in lower respiratory tract involvement

Severe pneumonia symptoms in infants, elderly, or immunocompromised patients

Rash in some cases (nonspecific viral exanthem)

Treatment is mainly supportive because adenoviral infection is usually self-limiting.

Antipyretics for fever (paracetamol preferred)

Nasal saline irrigation + gentle suction for children

Humidified air inhalation for airway comfort

Monitor for dehydration in gastroenteritis cases

Respiratory management:

Oxygen therapy if hypoxic

Nebulized saline for thick secretions

Avoid routine bronchodilators unless clear wheezing or reactive airway component

Monitor for respiratory distress in infants

Ocular management (conjunctivitis):

Cold compresses for discomfort

Artificial tears for irritation

Avoid steroid eye drops unless prescribed by ophthalmology

Highly contagious → advise hygiene and avoid contact sharing towels, makeup

Gastrointestinal management:

Oral rehydration solution (ORS)

IV fluids for moderate–severe dehydration

Avoid antimotility drugs in children

Antiviral therapy (only for severe / immunocompromised):

Cidofovir may be considered for life-threatening or disseminated adenovirus infection

Brincidofovir (less nephrotoxic) may be preferred in hematopoietic stem cell transplant settings

Strict renal monitoring if cidofovir is used

Management in immunocompromised:

Reduce immunosuppression if possible

Consider antiviral therapy early

Frequent monitoring of viral load by PCR (especially in transplant patients)

Hospitalization indications:

Persistent hypoxia or respiratory distress

Severe dehydration

Neurologic involvement (encephalitis, seizures)

Immunocompromised state with high viral load

Infants with severe pneumonia or apnea

Unless bacterial superinfection is clinically suspected.