Respiratory Viruses

Viral respiratory tract infections are the most common diseases affecting humans throughout the world. Laboratory testing to identify the specific pathogen is only necessary if clinical management would be altered; testing may also be indicated in certain populations to help with clinical decision making. Laboratory testing options include rapid antigen, direct fluorescent antibody (DFA), PCR, and culture.

  • 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 pathogen – necessary only if clinical management will be altered (eg, medication or disposition) or for epidemiological purposes (tracking epidemics such as Middle Eastern Respiratory Syndrome [MERS])
  • Testing is indicated in certain populations to help with clinical decision making
    • Influenza testing in at-risk patients with influenzalike symptoms
    • Infants presenting to the ER with severe respiratory infection – use respiratory syncytial virus (RSV) testing to assist with hospitalization or home management decision
    • 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

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 lower respiratory tract infections (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 of lower respiratory tract infection (LRTI) – >5 million/year in children <6 years in U.S.
  • 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 is less common – 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
    • Direct fluorescent antibody (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
      • Point-of-care tests for several clinically significant pathogens available
      • 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

Limitations 

Sensitivity of DFA methodology is dependent upon adequacy of specimen

If specimen contains fewer than 20 cells, then DFA result will be reported as "inadequate"

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

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

Guidelines

Ralston SL, Lieberthal AS, Meissner C, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, Phelan KJ, Zorc JJ, Stanko-Lopp D, Brown MA, Nathanson I, Rosenblum E, Sayles S, Hernandez-Cancio S, American Academy of Pediatrics. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014; 134(5): e1474-502. PubMed

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

Content Reviewed: 
October 2017

Last Update: October 2017