Respiratory Viruses

Viral respiratory tract infections are the most common diseases affecting humans throughout the world.

Epidemiology

Incidence
- Annually, >5 million children in the U.S. <6 years experience lower respiratory tract infections (LRTIs)
Age – bimodal peaks
- Adults >55 years
- For children, refer to Pediatrics tab

Organisms

Viruses are the fourth leading cause of hospital-treated pneumonia in otherwise healthy adults
Although a wide variety of viral agents are capable of causing LRTI, respiratory syncytial virus (RSV), adenovirus, influenza virus (A and B), and parainfluenza virus (1, 2, and 3) cause 80-90% of all LRTIs
- RSV and influenza are associated with significant annual morbidity and mortality, despite available therapies

Risk Factors

Age – <2 years or >55 years
Compromised immune system
Chronic medical condition (cardiac, pulmonary, hepatic)

Clinical Presentation

Clinical presentation often does not distinguish viruses
- Nonspecific symptoms – cough, fever, sore throat, rhinorrhea, hoarseness, bronchitis
- Individuals with compromised cardiac, pulmonary or immune systems and the elderly are at greatest risk for serious complications from LRTI

Clinical Background

Viral respiratory infection in children is responsible for more burden of disease than any other cause.

Epidemiology

Incidence
- Annually, >5 million children in the U.S. <6 years experience lower respiratory tract infections (LRTIs)
Age – peaks in children <10 years

Organisms

A wide variety of viral agents are capable of causing LRTIs in children; the following cause 80-90% of LRTIs
- Respiratory syncytial virus (RSV) and influenza A and B
  - RSV and influenza are viruses associated with significant annual morbidity and mortality, despite availability of therapies
  - RSV causes 50-90% of bronchiolitis infections and 5-40% of pneumonitis infections in children
- Adenovirus
- Parainfluenza 1, 2, 3
- Coronavirus
- Enterovirus
- Human metapneumovirus
- Rhinovirus

Clinical Presentation

Most respiratory viruses confined to upper respiratory tract
- Coryza, cough, hoarseness, rhinitis, pharyngitis, otitis
Lower respiratory tract involvement
- Tachypnea, wheeze, severe cough, croup, bronchiolitis, respiratory distress (nasal flaring, intercostal retraction)
Complications
- Severe viral pneumonia
- Acute respiratory failure
- Secondary bacterial pneumonia

Diagnosis

Indications for Testing

Severe LRTI

Laboratory Testing

In healthy infants, virological diagnosis generally not sought
Viral identification most important to rule out RSV, since it is treatable, and influenza in order to administer therapeutics and reduce morbidity and mortality
- Rapid antigen tests – often have low sensitivity
- DFA testing – rapid testing; frequently performed as panel
  - Requires nasopharyngeal swab or aspirate
- PCR testing
  - Requires nasopharyngeal swab or aspirate
  - Less rapid than DFA
  - More expensive
- Viral culture – gold standard but difficult to grow viruses
Nonspecific testing – CBC with differential
- Normal to low white blood cell count common
- Differential – usually monocytes and lymphocytes predominant

Indications for Testing

Symptoms of severe LRTI

Laboratory Testing

Testing to identify specific pathogens may not be necessary if clinical management is unchanged
- Exceptions – at-risk patients with influenza, hospitalized children with RSV
Nonspecific testing – CBC with differential
- Normal to low white blood cell count most common
- Differential – usually monocyte and lymphocyte predominant
Rapid antigen testing – often available as point-of-care test for influenza and RSV
- Sensitivity may be low when compared with other methods
Direct fluorescent antibody (DFA) stain
- Fairly rapid results (24 hours)
- Requires nasopharyngeal swab or aspirate
Polymerase chain reaction (PCR) available for many respiratory viruses
- More sensitive than DFA
- Longer turnaround time than DFA
- More expensive than DFA
Viral culture – gold standard
- Difficult to grow some viruses
- Not all viruses grow on same medium
- Time consuming, expensive

Imaging Studies

Chest x-ray usually demonstrates bilateral interstitial infiltrates
- Focal infiltrates are more suggestive of bacterial etiology

Differential Diagnosis

Tests generally appear in the order most useful for common clinical situations

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Predominance of monocytes and lymphocytes may be diagnostic; white blood cell count is usually not elevated

Test name: Respiratory Viruses DFA with Reflex to Respiratory Virus Mini Panel by RT-PCR

ARUP #: 2002565

Methodology: Direct Fluorescent Antibody Stain

Use:

DFA identifies the infectious agent of a pneumonia

Panel includes influenza A and B, parainfluenza (1,2,3), RSV, adenovirus, human metapneumovirus (hMPV)

If DFA is negative or inadequate for influenza, Respiratory Virus Mini Panel by RT-PCR will be added

Limitations:

Adequacy of the direct specimen significantly influences the sensitivity of DFA

Inadequate specimen collection or too few cells on the slide may lead to failure of direct smears

Test name: Respiratory Viruses DFA with Reflex to Viral Culture

ARUP #: 0060281

Methodology: Direct Fluorescent Antibody Stain

Use:

DFA identifies the infectious agent of a pneumonia

Panel includes influenza A and B, parainfluenza (1,2,3), RSV, adenovirus, human metapneumovirus (hMPV)

If DFA is negative or inadequate, a viral culture will be added

Limitations:

Adequacy of the direct specimen significantly influences the sensitivity of DFA

Inadequate specimen collection or too few cells on the slide may lead to failure of direct smears

Other viruses (eg, HSV, CMV) will not be routinely detected in this culture; decreased sensitivity for adenovirus using rapid culture

Sputum and nasal swabs are best specimens

Test name: Respiratory Virus Mini Panel by RT-PCR

ARUP #: 0060764

Methodology: Qualitative Reverse Transcription Polymerase Chain Reaction

Use:

Identify the agent of a pneumonia

RT-PCR is a rapid and highly sensitive test for viruses; RT-PCR is also the most expensive test

Components include testing for influenza A and B and RSV

Additional Tests Available

Test name: Respiratory Viruses Rapid Culture

ARUP #: 2001504

Methodology: Cell Culture/Immunofluorescence

Comments:

Isolate influenza A & B, RSV, adenovirus, and parainfluenza (1, 2, 3)

Test name: Respiratory Viruses DFA

ARUP #: 0060289

Methodology: Direct Fluorescent Antibody Stain

Comments:

Rapid test; detects adenovirus, influenza A & B, RSV, parainfluenza (1, 2, 3), hMPV

Significantly more rapid and less expensive than PCR

Test name: Human Metapneumovirus by DFA

ARUP #: 0060779

Methodology: Direct Fluorescent Antibody Stain

Comments:

Use to detect all types of hMPV (A1, A2, B1, B2)

No cross reactivity with other common respiratory viruses

Sample requires adequate amount of intact cells

Test name: Viral Culture

ARUP #: 0065008

Methodology: Cell Culture

Comments:

DFA preferred

Test name: Respiratory Culture (Includes Gram Stain 0060101)

ARUP #: 0060122

Methodology: Standard reference procedures for bacterial stain, aerobic culture, and identification. Sinus swabs or aspirates should be ordered as a Wound Culture (0060132).

Comments:

Test name: Influenza A H1N1 (2009) Detection by RT-PCR

ARUP #: 2004217

Methodology: Reverse Transcription Polymerase Chain Reaction

Comments:

Detect and type novel H1N1 virus