Respiratory Viruses

  • Diagnosis
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics
  • Videos

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
  • 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
  • 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

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

Explify Respiratory Pathogens by Next Generation Sequencing 2013694
Method: Massively Parallel Sequencing

Recommended Use 

Detect respiratory pathogens in patients with pneumonia

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

References from the ARUP Institute for Clinical and Experimental Pathology®

Graf EH, Simmon KE, Tardif KD, Hymas W, Flygare S, Eilbeck K, Yandell M, Schlaberg R. Unbiased detection of respiratory viruses by use of RNA sequencing-based metagenomics: a systematic comparison to a commercial PCR panel. J Clin Microbiol. 2016; 54(4): 1000-7. PubMed

Petti CA, Hillyard D. Value of RVP in clinical settings: older adults. J Clin Virol. 2007; 40 Suppl 1: S53-4. PubMed

Taggart EW, Crist G, Billetdeaux E, Langer J, Petti CA. Utility of terminal hemadsorption for detection of hemadsorbing respiratory viruses from conventional shell vial cultures for laboratories using R-Mix cultures. J Clin Virol. 2009; 44(1): 86-7. PubMed

Taggart EW, Hill HR, Martins TB, Litwin CM. Comparison of complement fixation with two enzyme-linked immunosorbent assays for the detection of antibodies to respiratory viral antigens. Am J Clin Pathol. 2006; 125(3): 460-6. PubMed

Medical Reviewers

Hillyard, David R., MD, Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Professor of Clinical Pathology, Adjunct Professor of Biology, University of Utah

Schlaberg, Robert, MD, MPH, Medical Director, Microbial Amplified Detection, Virology, and Fecal Chemistry; and Assistant Medical Director, Virology and Molecular Infectious Disease at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Last Update: August 2017