Respiratory Viruses

Diagnosis

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 – usually monocytes and lymphocytes predominate
  • Rapid antigen testing – often available as point-of-care test for influenza and RSV
    • Sensitivity may be low when compared with 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

Clinical Background

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 (LRTI)
  • Age – bimodal peaks
    • Adults >55 years
    • For children, refer to Pediatrics section

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 (types A and B), and parainfluenza virus (types 1, 2, and 3) cause 80-90% of all LRTI
    • 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

Pediatrics

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

Laboratory Testing

  • In healthy infants, specific virological diagnosis is generally unnecessary
  • Viral identification most important to rule out RSV (it is treatable) and influenza (in order 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
  • Nonspecific testing – CBC with differential
    • Normal-to-low white blood cell count – common
    • Differential – usually monocytes and lymphocytes predominate

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Respiratory Viruses DFA with Reflex to Respiratory Virus Mini Panel by PCR 2002565
Method: Direct Fluorescent Antibody Stain/Qualitative Polymerase Chain Reaction

Identify the viral agent of a pneumonia

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

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

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

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

Identify the viral agent of a pneumonia – most useful in immunocompromised patients

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

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

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

Identify the viral agent of a pneumonia

Components include testing for RSV and influenza types A and B

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Predominance of monocytes and lymphocytes may be diagnostic

White blood cell count – usually not elevated

Respiratory Viruses Rapid Culture 2001504
Method: Cell Culture/Immunofluorescence

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

Respiratory Viruses DFA 0060289
Method: Direct Fluorescent Antibody Stain

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

Significantly more rapid and less expensive than PCR

High false-negative rate, depending on virus

Recommended for specimens other than CSF

Human Metapneumovirus DFA  0060779
Method: Direct Fluorescent Antibody Stain

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

Recommended for specimens other than CSF

Viral Culture, Respiratory 2006499
Method: Cell Culture

Viruses that can be isolated – adenovirus; CMV; enterovirus; HSV; influenza A and B; parainfluenza types 1, 2, 3; RSV; and VZV

Virus-specific tests are recommended

Respiratory Culture and Gram Stain 0060122
Method: Stain/Culture/Identification
Influenza A Virus H1/H3 Subtyping by Real-Time RT-PCR  2007469
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Identify H3 and 2009-H1 hemagglutinin genes

Current circulating influenza A strains are detected and typed (H1N1 and H3N2); however, other H1 and H3 subtypes may also be detected