Respiratory Viruses

Indications for Testing

Symptoms of severe infection of lower respiratory tract

Laboratory Testing

Testing to identify specific pathogens may be unnecessary if clinical management would be unchanged
- Exceptions – at-risk patients with influenza, hospitalized children with respiratory syncytial virus (RSV), immunocompromised patients
Nonspecific testing – CBC with differential
- Normal-to-low white blood cell count – most common
- Differential – monocytes and lymphocytes predominate
Rapid antigen testing – often available as point-of-care test for influenza and RSV
- Sensitivity may be low when compared to other methodologies
Direct fluorescent antibody (DFA) stain
- Fairly rapid results (24 hours)
- Requires nasopharyngeal swab or aspirate
  - Less sensitive than polymerase chain reaction (PCR)
PCR tests 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

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

Epidemiology

Age – bimodal peaks
- Adults >55 years
- Children – refer to Pediatrics section

Organisms

Viruses are the fourth-leading cause of hospital-treated pneumonia in otherwise healthy adults
Most common agents of LRTI
- Influenza
- Parainfluenza (types 1,2,3)
- Adenovirus
- RSV
Emerging viral agents
- Middle East respiratory syndrome coronavirus (MERS-CoV)
- Severe acute respiratory distress syndrome coronavirus (SARS-CoV)
- Human bocavirus (HBoV1)

Risk Factors

Age – <2 years or >55 years
Immunocompromised status
Chronic medical condition – cardiac, pulmonary, hepatic

Clinical Presentation

Clinical presentation often does not distinguish viruses
- Cough, fever, sore throat, rhinorrhea, hoarseness, bronchitis
- Individuals with chronic cardiac or pulmonary disease, immunocompromised state, or the elderly are at greatest risk for serious complications from LRTI
- Secondary bacterial pneumonia
- Severe viral pneumonia
- Acute respiratory failure

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 (LRTI)
Age – peaks in children <10 years

Organisms

A wide variety of viral agents are capable of causing LRTI in children
80-90% of LRTI are caused by the following
- Rhinovirus
- 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
- Enterovirus
- Parainfluenza 1, 2, 3
- Adenovirus type 14
- Human metapneumovirus

Clinical Presentation

Most respiratory viruses are 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
Immunocompromised status

Laboratory Testing

In healthy infants, specific virological diagnosis is generally unnecessary
Nonspecific testing – CBC with differential
- Normal-to-low white blood cell count – common
- Differential – monocytes and lymphocytes predominate
Viral identification most important to rule out RSV (predominately in hospitalized patients) and influenza (to administer antiviral agents)
- Rapid antigen tests – often have low sensitivity
- DFA testing – rapid results; frequently performed as a panel
  - Requires nasopharyngeal swab or aspirate
  - Best yield if combined with reflex to polymerase chain reaction (PCR)
- PCR testing
  - Requires nasopharyngeal swab or aspirate
  - Takes longer than DFA
  - More expensive than DFA
- Viral culture – gold standard, but viruses are difficult to grow

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Respiratory Viruses DFA with Reflex to Viral Culture, Respiratory 0060281
Method: Direct Fluorescent Antibody Stain/Cell Culture

Recommended Use

Order this test when the detection of respiratory viruses in addition to influenza is important

Molecular methods are preferred for immunocompromised and hospitalized patients; for general inpatient workup of influenza-like illness, order the respiratory virus mini panel by PCR

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

Reflex pattern – if DFA is negative or inadequate, then a respiratory 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

Longer time for results than by reflex PCR

Respiratory Virus Mini Panel by PCR 0060764
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Recommended Use

Preferred test to confirm respiratory syncytial virus (RSV) or influenza in general inpatients and RSV in adults

Components include testing for RSV and influenza types A and B

General References

Buller RS. Molecular detection of respiratory viruses. Clin Lab Med. 2013; 33(3): 439-60. PubMed

Caliendo AM. Multiplex PCR and emerging technologies for the detection of respiratory pathogens. Clin Infect Dis. 2011; 52 Suppl 4: S326-30. PubMed

Carman WF, Mahony JB. The pathogens. J Clin Virol. 2007; 40 Suppl 1: S5-S10. PubMed

Dunn JJ, Miller MB. Emerging respiratory viruses other than influenza. Clin Lab Med. 2014; 34(2): 409-30. PubMed

Mahony JB, Petrich A, Smieja M. Molecular diagnosis of respiratory virus infections. Crit Rev Clin Lab Sci. 2011; 48(5-6): 217-49. PubMed

McAdam AJ, Riley AM. Developments in tissue culture detection of respiratory viruses. Clin Lab Med. 2009; 29(4): 623-34. PubMed

Mizgerd JP. Acute lower respiratory tract infection. N Engl J Med. 2008; 358(7): 716-27. PubMed

Murdoch DR, Jennings LC, Bhat N, Anderson TP. Emerging advances in rapid diagnostics of respiratory infections. Infect Dis Clin North Am. 2010; 24(3): 791-807. PubMed

Pavia AT. Viral infections of the lower respiratory tract: old viruses, new viruses, and the role of diagnosis. Clin Infect Dis. 2011; 52 Suppl 4: S284-9. PubMed

Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011; 377(9773): 1264-75. PubMed

Talbot K, Falsey AR. The diagnosis of viral respiratory disease in older adults. Clin Infect Dis. 2010; 50(5): 747-51. PubMed

Templeton KE. Why diagnose respiratory viral infection? J Clin Virol. 2007; 40 Suppl 1: S2-4. PubMed

Tregoning JS, Schwarze J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev. 2010; 23(1): 74-98. PubMed