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 – 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

Clinical Background

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

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
  • 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

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 Viral Culture, Respiratory 0060281
Method: Direct Fluorescent Antibody Stain/Cell Culture

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

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

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

   
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

Detects common respiratory viruses

Offers improved turnaround time over respiratory viral culture; molecular methods may offer improved sensitivity

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

Respiratory Viruses DFA with Reflex to Respiratory Virus Mini Panel by PCR 2002565
Method: Direct Fluorescent Antibody Stain/Qualitative Polymerase Chain Reaction

Not a recommended test

Identify the viral agent of a pneumonia

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

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

Reflex pattern – if DFA is negative or inadequate for influenza, Respiratory Virus Mini Panel by RT-PCR will be added

Respiratory Viruses DFA 0060289
Method: Direct Fluorescent Antibody Stain

Not a preferred stand-alone test

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

Preferred initial test to detect human metapneumovirus (hMPV) in children and adults

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

Detects common respiratory viruses as well as HSV and VZV

Molecular methods may offer improved sensitivity; respiratory viruses rapid culture offers faster turnaround time

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

Follow-up test for patients with documented influenza A

Not a first-line test for the detection of suspected influenza in most clinical situations

Detects and subtypes the 2 predominant strains of circulating influenza A (H1N1 and H3N2)