When should I test for influenza in a patient with fever and cough, sore throat, or myalgias that began within the past 48 hours, especially if they are ≥65 years old, pregnant, have chronic heart, lung, kidney, liver, or neurologic disease, diabetes, obesity (BMI ≥ 30), immunosuppression, are a child <2 years, are hospitalized, or have severe respiratory symptoms such as dyspnea, hypoxia, or altered mental status?

When to Test for Influenza

You should test for influenza in all high-risk patients presenting with acute respiratory symptoms during influenza season, including those ≥65 years, pregnant women, children <2 years, immunocompromised individuals, and those with chronic cardiopulmonary, metabolic, neurologic, or liver disease—and you should test immediately upon presentation without waiting, as testing results will guide antiviral treatment decisions that are most effective when started within 24-48 hours of symptom onset. 1

High-Risk Outpatients Who Should Be Tested

During influenza season, you must test the following high-risk outpatients:

• Immunocompromised patients presenting with influenza-like illness, pneumonia, or even nonspecific respiratory illness such as cough without fever 1
• Adults ≥65 years old with acute respiratory symptoms, as they account for >90% of influenza-related deaths and have diminished febrile responses that make clinical diagnosis unreliable 2, 3
• Pregnant women and those within 2 weeks postpartum with respiratory symptoms 1
• Children <2 years old, who have hospitalization rates of 200-1,000 per 100,000 population comparable to elderly patients 2
• Patients with chronic conditions including asthma, COPD, heart failure, diabetes, obesity (BMI ≥30), chronic kidney disease, liver disease, or neurologic disorders who present with acute respiratory symptoms or exacerbation of their underlying condition 1, 4
• Patients with severe respiratory symptoms including dyspnea, hypoxia, or altered mental status regardless of age 1

The Infectious Diseases Society of America emphasizes that testing should occur if results will influence clinical management, which in high-risk patients almost always means initiating antiviral therapy 1.

All Hospitalized Patients Should Be Tested

During influenza activity, test all patients requiring hospitalization with:

• Any acute respiratory illness including pneumonia, with or without fever 1
• Acute worsening of chronic cardiopulmonary disease (COPD, asthma, coronary artery disease, heart failure), as influenza frequently triggers exacerbations 1
• Acute onset of respiratory symptoms in immunocompromised patients, even without fever, as manifestations are frequently atypical in this population 1
• New respiratory symptoms or distress developing during hospitalization without a clear alternative diagnosis 1

Even during periods of low influenza activity, you should still test hospitalized patients with acute respiratory illness who have epidemiological links to influenza 1.

Timing of Testing

Collect specimens as soon after illness onset as possible, preferably within 4 days of symptom onset 1. This timing is critical because:

• Antiviral treatment provides greatest benefit when started within 24 hours of symptom onset 1, 5
• Treatment within 48 hours still provides meaningful benefit and should not be withheld 1
• Viral shedding is highest early in illness, improving test sensitivity 1

Do not delay antiviral treatment while awaiting test results in high-risk patients—start empiric treatment immediately if clinical suspicion is high during influenza season 1.

Optional Testing in Lower-Risk Outpatients

You can consider testing in patients not at high risk for complications if:

• Results might influence antiviral treatment decisions 1
• Testing could reduce unnecessary antibiotic use or further diagnostic workup 1
• Results might guide chemoprophylaxis decisions for high-risk household contacts 1
• Testing could reduce time in the emergency department 1

However, the strength of this recommendation is weaker (C-III evidence) compared to testing high-risk patients 1.

Critical Pitfalls to Avoid

Do not rely on clinical diagnosis alone in high-risk patients. Clinical case definitions have poor performance, with sensitivity of only 63-78% and specificity of 55-71% compared to viral culture 2. The commonly used definition of fever ≥37.8°C plus cough has only 57% sensitivity in older adults 3.

Do not assume absence of fever rules out influenza, especially in:

• Elderly patients (≥65 years), who may have blunted febrile responses—consider lower fever thresholds of 37.3°C in this population 3
• Immunocompromised patients, who frequently present atypically 1
• Young children, who may present with irritability, poor feeding, or signs mimicking bacterial sepsis rather than classic influenza symptoms 1, 2

Do not use rapid antigen tests (RIDTs) in hospitalized patients except when more sensitive molecular assays are unavailable, as RIDTs have suboptimal sensitivity (10-80%) and require confirmatory RT-PCR testing if negative 1, 6. Rapid molecular assays are preferred, with 86-100% sensitivity 1, 5.

Do not wait for "typical" influenza symptoms before testing high-risk patients. Among hospitalized adults with confirmed influenza, only 44-51% had typical influenza-like illness symptoms 1. Influenza should be considered in any patient with respiratory symptoms or fever during influenza season 1.

Specimen Collection

Collect nasopharyngeal specimens preferentially over other upper respiratory tract specimens to maximize viral detection 1. If nasopharyngeal specimens are unavailable, combine nasal and throat swabs together rather than using single specimens 1. Use flocked swabs over non-flocked swabs to improve detection 1.

For hospitalized patients with respiratory failure on mechanical ventilation, collect endotracheal aspirate or bronchoalveolar lavage specimens, especially if upper respiratory tract specimens are negative 1.