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.

Tabs Content

Clinical Overview

Diagnosis

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

Background

Epidemiology

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

Organisms

Viruses are the fourth-leading cause of hospital-treated pneumonia in otherwise healthy adults
Most common agents of lower respiratory tract infections (LRTI)
- Influenza
- Parainfluenza (types 1, 2, 3)
- Adenovirus
- Respiratory syncytial virus (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

Pediatrics

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

80-90% of LRTI are caused by a wide variety of pathogens, including
- Rhinovirus
- Respiratory syncytial virus (RSV)
  - Causes 50-90% of bronchiolitis infections and 5-40% of pneumonitis infections in children
  - Associated with significant annual morbidity and mortality, despite availability of therapies
- Influenza A and B – associated with significant annual morbidity and mortality, despite availability of therapies
- 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 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

ARUP Lab Tests

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 detection of respiratory viruses in addition to influenza is important

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

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

Reflex pattern – if direct fluorescent antibody (DFA) is negative or inadequate, then a respiratory viral culture will be added

Limitations

Sensitivity of DFA methodology is dependent on 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

Recommended Use

Preferred test to confirm RSV or influenza in general inpatients and RSV in adults

Components include testing for RSV and influenza (A, B)

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

Recommended Use

Detect respiratory pathogens in patients with pneumonia

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

References

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

Educational Videos

(60 min)

Content Review:

October 2017

Last Update: March 2018


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	Respiratory Viruses. ARUP Consult^©. Retrieved May 14, 2018, from: https://arupconsult.com/content/respiratory-viruses

Respiratory Viruses

Diagnosis

Indications for Testing

Laboratory Testing

Imaging Studies

Differential Diagnosis

Background

Epidemiology

Organisms

Risk Factors

Clinical Presentation

Pediatrics

Clinical Background

Epidemiology

Organisms

Clinical Presentation

Diagnosis

Indications for Testing

Laboratory Testing

ARUP Lab Tests

Medical Reviewers

References

Guidelines

General References

References from the ARUP Institute for Clinical and Experimental Pathology®

References from the ARUP Institute for Clinical and Experimental Pathology^®