What is the most likely diagnostic test to confirm influenza in an elderly patient with fever, chills, myalgia, and bilateral interstitial infiltrates on chest radiograph, given a negative SARS-CoV-2 PCR test?

Diagnostic Testing for Influenza in an Elderly Patient with Severe Respiratory Illness

PCR of nasopharyngeal swab for influenza (Option B) is the most appropriate diagnostic test for this elderly patient with severe respiratory illness and bilateral infiltrates. 1

Rationale for PCR Over Other Options

The American Thoracic Society explicitly recommends that adults with community-acquired pneumonia should have respiratory samples tested for influenza virus using rapid influenza molecular assays such as nucleic acid amplification tests (NAATs) over rapid antigen tests when influenza viruses are circulating in the community 1. This recommendation is particularly critical given this patient's:

• Severe presentation with hypoxemia (84% oxygen saturation) 1
• High-risk comorbidities including diabetes, hypertension, and chronic kidney disease 1
• Bilateral interstitial infiltrates suggesting viral pneumonia 1
• Presentation during typical influenza season 2

Why Rapid Antigen Testing (Option C) is Inadequate

Rapid antigen tests have unacceptably low sensitivity in elderly adults, ranging from only 40-80% 1, 2. This poor sensitivity is particularly problematic in:

• Frail elderly patients who may have lower viral loads 1
• Severe cases where false-negative results could delay critical antiviral therapy 1
• Patients presenting beyond 24-48 hours of symptom onset, when viral shedding may be decreasing 1

Research confirms this limitation, with one study showing rapid antigen test sensitivity of only 20% compared to PCR in returning travelers with influenza 3. Another study demonstrated significantly better performance with nasopharyngeal specimens (58.9% sensitivity) compared to oropharyngeal specimens (10.3% sensitivity) for rapid antigen tests 4.

Why Other Options Are Not Optimal

Sputum Culture (Option A)

• Not indicated for viral respiratory infections 1
• Primarily used for bacterial pneumonia diagnosis 1
• Would miss the viral etiology entirely 1

Serum Influenza Antibodies (Option D)

• Not useful for acute diagnosis as antibody response takes days to weeks to develop 2
• Only valuable for epidemiological studies, not clinical decision-making 2
• Would not guide immediate antiviral therapy 1

Bronchoscopy and BAL (Option E)

• Unnecessarily invasive for initial diagnosis 1
• Reserved for immunocompromised patients or when upper respiratory testing is negative despite high clinical suspicion 2
• Not first-line in immunocompetent patients 1
• While BAL has higher sensitivity in critically ill patients (88.9% vs 15% for nasal wash in one study) 2, the risk-benefit ratio does not favor this approach as initial testing 1

Critical Clinical Context

The Infectious Diseases Society of America guidelines emphasize that influenza causes substantial morbidity and mortality in elderly patients, with complication rates approaching 32%, pneumonia rates of 7%, hospitalization rates of 4%, and mortality rates of 4% in long-term care facilities 1. This patient's severe presentation with:

• Hypoxemia requiring supplemental oxygen 1
• Bilateral infiltrates suggesting diffuse viral pneumonia 1
• Multiple high-risk comorbidities 1

...makes rapid and accurate diagnosis essential for initiating antiviral therapy, which is most effective when started within 48 hours of symptom onset 1.

Specimen Collection Best Practices

Nasopharyngeal swabs are the preferred specimen for influenza PCR testing because they:

• Are simpler to perform than nasopharyngeal washes with acceptable sensitivity 1
• Detect viral RNA better in the early disease stage compared to oropharyngeal specimens 1
• Should be combined in viral transport media and transported on ice within 1-2 hours for optimal results 1

Common Pitfalls to Avoid

• Do not rely on negative rapid antigen tests to rule out influenza in elderly patients with severe illness 1, 2
• Do not delay testing beyond 24-48 hours of symptom onset when viral isolation is most successful 1
• Do not use clinical features alone to distinguish influenza from other respiratory viruses, as overlap is substantial 2
• Do not accept oropharyngeal specimens when nasopharyngeal swabs are feasible, as sensitivity is significantly lower 4