As winter approaches, so does the annual onset of rising respiratory infections and the accompanying challenge of overlapping symptoms. From runny noses and sore throats to fever and chills, this common set of symptoms may suggest a range of infections including influenza, respiratory syncytial virus (RSV), and COVID-19. Understanding the targeted respiratory testing available can help physicians navigate the seasonal surge of respiratory symptoms, providing clarity and confidence in the diagnosis and treatment of affected patients.
In this article:
Clinical challenge | Why it matters | Ordering recommendations | Interpreting test results | Next steps | Supporting resources
Clinical challenge: RSV, COVID, flu, and other contagious respiratory infections share common symptoms
Due to relatively predictable seasonal patterns, fall and winter are known in the US to be respiratory disease season.1
Winter continues to be the highest risk period for severe respiratory disease in older adults and young children, driven largely by influenza, RSV, and SARS-CoV-2, which the CDC identifies as major fall and winter respiratory illnesses.2
Despite the familiarity of these illnesses, differentiation and accurate diagnosis can be challenging due to the core ensemble of symptoms they share, including
- Fever or chills
- Cough
- Shortness of breath or difficulty breathing
- Fatigue
- Sore throat
- Runny or stuffy nose
- Muscle pain or body aches
- Headache
- Vomiting and diarrhea (more common in children)
Other viral infections sharing these symptoms include
- Rhinovirus and enterovirus (common cold viruses): Often cause cough, sore throat, runny or stuffy nose, headache, and mild fever, and in practice can be indistinguishable from mild flu, COVID-19, or RSV
- Seasonal human coronaviruses (non-SARS-CoV-2): Cause upper respiratory tract infections with cough, sore throat, nasal congestion, and low-grade fever, overlapping heavily with mild COVID-19 and flu presentations
- Human metapneumovirus (hMPV): Produces bronchiolitis and pneumonia in children and respiratory illness in adults, with cough, dyspnea, wheeze, and fever similar to RSV and influenza
- Parainfluenza viruses: Classically associated with croup in children, but also cause bronchitis, bronchiolitis, and pneumonia; symptoms include fever, cough, hoarseness, and respiratory distress
- Adenovirus (respiratory serotypes): Can cause pharyngitis, conjunctivitis, and pneumonia, with fever, sore throat, cough, and systemic symptoms resembling influenza or COVID-19, particularly in institutional outbreaks
For most age groups, it’s difficult to reliably distinguish flu, COVID-19, RSV, and these other infections based on symptoms alone.
For accurate identification of infections, 2 main categories of tools are critical for diagnosis, development of an appropriate care plan, and infection-control decisions.
Diagnostic testing
- Rapid antigen tests
- PCR panels
Epidemiologic context
- Season
- Known circulation patterns
- Exposure history
Why it matters: Respiratory infections can cause severe illness for young children, older adults, and other higher-risk individuals
The CDC advises that testing for respiratory viruses when a patient is feeling sick can help guide treatment decisions, and may be especially helpful for those at higher risk for getting very sick.3
Those at higher risk include older adults ≥65 and children <2 as well as people with certain medical conditions, including those with weakened immune systems, people with disabilities, and pregnant women.2,4
Increased risks for patients ≥65
Most deaths from respiratory viruses occur in people older than 65, with risk increasing significantly with advancing age.4 In addition to having immune systems that change and weaken over time, people aged 65 and older are more likely to have underlying health conditions.
Increased risks for young patients
Viruses that affect airways can present more of a health threat for young children and particularly infants, as their lungs and airways are smaller. In addition, their immune systems are still developing and may be less capable of combating disease.4
Even for those not in higher-risk groups, testing for respiratory infection when feeling sick can help patients seek appropriate treatment more promptly and take steps to avoid spreading respiratory viruses to others.3
Ordering recommendations: Molecular testing to detect and identify respiratory virus(es)
Quest offers nucleic acid amplification tests (NAATs) such as polymerase chain reaction (PCR) tests to help identify viral infections and establish a reliable basis for treatment decisions.
Antigen tests for flu and COVID-19 infections are another option as they typically return results quickly. However, they are not as sensitive as NAATs, which include PCR tests to detect actual genetic material of the virus.3
Recommended tests: Molecular respiratory pathogen panels and tests
- Test code: 31688
- CPT® code: 87636*
To meet regulatory reporting requirements for COVID-19 testing, the patient’s address, phone number, and other demographic details are required for this order.
- Test code: 39816
- CPT code: 87637
To meet regulatory reporting requirements for COVID-19 testing, the patient’s address, phone number, and other demographic details are required for this order.
- Test code: 91989
- CPT code: 87631*
- Test code: 11365
- CPT code: 87798* (x2)
* CPT Code is subject to a Medicare Limited Coverage Policy and may require a signed ABN when ordering.
Interpreting test results: Incorporating individual patient context to support respiratory infection diagnosis
Qualitative NAAT/PCR test results should be interpreted as detected or not detected rather than by viral load.5-8
- A positive result for SARS-CoV-2, influenza A or B, RSV, or Bordetella pertussis/parapertussis supports active or very recent infection and should be interpreted in the context of symptoms, timing, and exposure history.5-8
- A negative result lowers the likelihood of that pathogen, but does not completely exclude infection if the specimen was collected too early or too late, or if it was suboptimal.5-8
If more than one target is detected, coinfection is possible and the clinician should not assume a single virus explains the entire presentation.5-8
Next steps: Appropriate treatments, infection control, and repeat testing
When SARS-CoV-2 or influenza is detected, assess promptly for isolation guidance, antiviral eligibility, and risk to household or close contacts.5-7
If RSV is detected, management is usually supportive, but severity assessment is important in the case of infants, frail older adults, and patients with cardiopulmonary disease.5-7
A positive Bordetella pertussis/parapertussis result should prompt treatment, consideration of post-exposure prophylaxis for close contacts when indicated, and any required public health reporting.8
If the test is negative but clinical suspicion remains high, consider repeat testing or a broader respiratory pathogen evaluation, particularly if symptoms are evolving.5-8
Supporting resources
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