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Respiratory Viruses. ARUP Consult©. Retrieved April 09, 2020, https://arupconsult.com/content/respiratory-viruses

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Respiratory Viruses

Viral respiratory tract infections are the most common diseases affecting humans worldwide. Respiratory viruses can be associated with both self-limiting upper respiratory tract infections (eg, the common cold) and more severe lower respiratory tract infections (LRTIs) (eg, bronchitis, bronchiolitis, pneumonitis, pneumonia).  LRTIs are a major cause of hospitalization, morbidity, and mortality in infants and the elderly and are associated with significant disease burden.  

Laboratory testing to identify the specific pathogen causing the respiratory illness is only necessary if clinical management would be altered; for example, testing for the influenza virus during the flu season can help to determine whether antiviral treatment should be administered.  Respiratory virus testing may also be indicated in certain populations (eg, infants, immunocompromised persons, the elderly) to help with patient management, epidemiologic surveillance, and infection control measures.  Laboratory testing options include rapid antigen detection tests (RADTs), direct fluorescent antibody (DFA) and polymerase chain reaction (PCR) tests, and viral culture.

Quick Answers for Clinicians

Is laboratory testing available for SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19)? Who should be tested for SARS-CoV-2?

Yes, testing is available through the CDC and state health departments. Due to supply constraints,  limits on capacity, and extraordinary demand for testing, ARUP can no longer accept orders for the 2019 Novel Coronavirus SARS-CoV-2 by PCR test. The environment surrounding COVID-19 testing is evolving rapidly. Please refer to ARUP’s Response to Coronavirus Disease 2019 (COVID-19) page for the most up-to-date information.

Testing to determine possible SARS-CoV-2 infection should be limited to specimens collected from patients meeting CDC clinical and epidemiologic criteria. Efforts to contain the spread and mitigate the impact of the virus are rapidly evolving. For the most up-to-date information, refer to the ARUP Consult COVID-19 topic and theCDC’s guidance for healthcare professionals. 

Who should be tested for respiratory virus infection?

Unless testing is performed for epidemiologic purposes, testing is generally indicated only for the following populations:

  • At-risk patients with influenzalike symptoms (during flu season); refer to the ARUP Consult® Influenza topic for more information
  • Infants and children presenting with severe respiratory infection (respiratory syncytial virus [RSV] testing is indicated); refer to the ARUP Consult Respiratory Syncytial Virus topic for more information
  • Immunocompromised patients
What tests are available to detect respiratory viruses?

Point-of-care and near-point-of-care tests are available for respiratory syncytial virus (RSV) (certain rapid antigen detection tests [RADTs]) and influenza virus (polymerase chain reaction [PCR] tests and RADTs). Direct fluorescent antibody (DFA) testing is available for influenza, RSV, adenovirus, and human metapneumovirus (hMPV). PCR testing can detect the most common respiratory viruses and, if identifying the specific pathogen is important for treatment, is typically the recommended methodology. However, if a strong suspicion for a particular agent is present, testing for that pathogen alone may be indicated (refer to specific virus information in the Laboratory Testing section below).

What is the role of next generation sequencing (NGS) tests in respiratory viruses?

Next generation sequencing (NGS) is a rapidly evolving methodology that may be available at some laboratories. NGS tests might be considered when more traditional panel test results are negative and serious suspicion of infectious disease remains, and when identification of the underlying etiologic agent causing the illness may change or impact patient management. However, negative NGS test results do not definitively rule out viral, bacterial, or fungal infections. Targeted polymerase chain reaction (PCR)-based tests are generally more sensitive and are preferred when specific pathogens are suspected.

Indications for Testing

Although testing to identify a specific pathogen is not often indicated, it can be useful if the specific diagnosis will alter clinical management. Testing for respiratory viruses in general is indicated for immunocompromised patients presenting with severe LRTI. Influenza testing is indicated in at-risk patients with influenzalike symptoms, and respiratory syncytial virus (RSV) testing is indicated in infants and children presenting with severe respiratory infection. For more detailed indications, refer to the Influenza and Respiratory Syncytial Virus Consult topics.

Laboratory Testing

Diagnosis

Influenza Virus

Influenza (commonly referred to as the flu) is an acute viral infection that is highly transmissible, leading to outbreaks of varying severity during the winter in temperate regions. In most healthy individuals, the flu is self-limited and uncomplicated, but in high-risk patients, it can lead to serious complications.  The Infectious Diseases Society of America (IDSA) recommends testing if the results will influence management decisions, such as whether to initiate antiviral therapy.  If available, the near-point-of-care PCR test is preferred for diagnosis because of its rapid results and reasonably high sensitivity. For more information, refer to the Influenza Virus topic.

Respiratory Syncytial Virus

RSV is one of the most common agents of lower respiratory illnesses (including bronchiolitis and pneumonia) in infants and children worldwide. Laboratory testing is only indicated when diagnosis would change the course of patient management.  For immunocompetent children, DFA testing and RADTs have adequate sensitivity.   However, for adults and for all hospitalized and immunocompromised patients, the more sensitive PCR test is preferred.  For more information, refer to the Respiratory Syncytial Virus topic.

Parainfluenza Virus

Parainfluenza virus is a common cause of croup (laryngotracheobronchitis), bronchiolitis, pneumonia, and upper respiratory tract infections.  Clinical diagnosis is usually sufficient. If laboratory testing is necessary, consider concurrent DFA testing for other common respiratory viruses (eg, influenza, adenovirus, RSV). PCR testing is more expensive and less rapid than DFA testing, but unlike DFA, can detect the less common parainfluenza type 4.

Adenovirus

Adenoviruses usually cause mild, self-limiting respiratory illnesses, primarily in children. In immunocompetent patients, the diagnosis is typically based on clinical presentation. In immunocompromised individuals, adenovirus may cause severe, fatal disease, and laboratory testing is indicated.  PCR testing is the preferred method for detecting adenovirus in this group.

Human Metapneumovirus

Human metapneumovirus (hMPV) is an agent of acute respiratory tract disease in people of all ages. The virus has been associated with bronchiolitis in infants and pneumonia, exacerbations of asthma and croup, and upper respiratory infections in children.  Clinical presentation ranges from the common cold to pneumonia. When testing is indicated, DFA testing is generally preferred; PCR testing may be considered when DFA test results are negative but suspicion of infection is high. Because coinfection with other respiratory viruses is common, concurrent viral testing should be considered.

Laboratory Tests for Common Respiratory Viruses

Etiologic Agent Laboratory Testing
  Point-of-Care or Near-Point-of-Care Tests Singleplex/Multiplex PCR DFA Viral Culture
Influenza virus A and B xa x xb x
RSV xc x xb x
Parainfluenza virus   x xd xd
Adenovirus   x x x
hMPV   x xb  
Coronaviruses, rhinovirus, bocavirus   x    
aPCR and RADTs available

bRapid DFA

cRADT available

dFor types 1, 2, and 3; type 4 is only detectable using PCR

Sources: Ginocchio ; Henrickson ; Miller ; Loeffelholz 

Comparison of Testing Methodologies

Test Methodology Advantage(s) Disadvantage(s)
RADTs Often available as point-of-care test for influenza and RSV

Rapid turnaround time (<30 min)

Acceptable sensitivity and specificity in young children

 Sensitivity may be low when compared to other methodologies, especially in adults

False-negative results are possible
DFA testing Useful in infants and children due to high sensitivity and specificity in this patient population

Shorter turnaround time than viral culture or PCR

Less expensive than PCR or culture

 May not be available for less common respiratory viruses, thus requiring NAAT

Sensitivity may be low when compared to other methodologies, especially in adults

Adequate specimen influences sensitivity of the assay

False-negative results are possible

Negative results may be confirmed with culture or NAAT if high suspicion remains
PCR testing/NAAT Very high sensitivity and specificity

PCR panels can detect other respiratory viruses

Low likelihood of false-positive or false-negative result

Detects viruses in adults and older children, despite their lower viral shedding

 Longer turnaround time than DFA

More expensive than DFA

May detect virus after the infection has been cleared
Viral culture Traditional gold standard for diagnosis

May aid in detecting coinfections

Virus can be stored for diagnostic studies

High specificity

 Long turnaround time

May require specific media for each virus

Lower sensitivity
Serologic testing n/a Not useful for diagnosis
n/a, not applicable; NAAT, nucleic acid amplification testing

Sources: Chartrand ;  Henrickson 

ARUP Lab Tests

Recommended Testing

Preferred testing for RSV and influenza in general inpatients and adults

Preferred testing for broad respiratory viruses (including RSV and influenza) in high-risk patients

Rapid detection of RSV in children

Other Testing

Polymerase Chain Reaction
Direct Fluorescent Antibody

AlertThis test has been temporarily inactivated. In compliance with guidance issued by government agencies, respiratory viral cultures are being temporarily discontinued for the safety of laboratory staff during the COVID-19 pandemic. PCR testing is available for a variety of specific viruses; refer to the Laboratory Test Directory.

AlertThis test has been temporarily inactivated. In compliance with guidance issued by government agencies, respiratory viral cultures are being temporarily discontinued for the safety of laboratory staff during the COVID-19 pandemic. PCR testing is available for a variety of specific viruses; refer to the Laboratory Test Directory.

Rapid Culture

AlertThis test has been temporarily inactivated. In compliance with guidance issued by government agencies, respiratory viral cultures are being temporarily discontinued for the safety of laboratory staff during the COVID-19 pandemic. PCR testing is available for a variety of specific viruses; refer to the Laboratory Test Directory.

AlertThis test has been temporarily inactivated. In compliance with guidance issued by government agencies, respiratory viral cultures are being temporarily discontinued for the safety of laboratory staff during the COVID-19 pandemic. PCR testing is available for a variety of specific viruses; refer to the Laboratory Test Directory.

AlertThis test has been temporarily inactivated. In compliance with guidance issued by government agencies, respiratory viral cultures are being temporarily discontinued for the safety of laboratory staff during the COVID-19 pandemic. PCR testing is available for a variety of specific viruses; refer to the Laboratory Test Directory.

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References

Resources from the ARUP Institute for Clinical and Experimental Pathology®

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