Yes, Test for COVID-19 Even When Influenza is Positive
Patients who test positive for influenza should still be tested for SARS-CoV-2, as coinfection can occur and significantly worsens outcomes, including a nearly 6-fold increased risk of death. 1
Why Testing for Both Matters
The evidence clearly demonstrates that influenza positivity does not exclude COVID-19 coinfection. A critical 2021 study found that patients with both infections had a risk of death 5.92 times greater (95% CI: 3.21-10.91) compared to those with neither infection 1. These coinfected patients also showed the highest odds of requiring ventilator support and ICU admission.
Coinfection is Not Rare
While some studies show variable coinfection rates (ranging from 2.2% to occasional cases) 2, 3, the clinical impact when it does occur is severe enough to warrant routine testing:
- A 2024 study documented 44 coinfected cases with a 50% mortality rate among hospitalized coinfected patients 2
- Hospitalized coinfected patients had significantly longer disease duration (19.86 ± 10.78 days) compared to outpatients (7.63 ± 2.25 days) 2
- The presence of one respiratory pathogen does not exclude the other—Italian data during peak pandemic showed no significant difference in SARS-CoV-2 rates between patients with or without other respiratory pathogens 4
Clinical Algorithm for Testing
For symptomatic patients:
- Test for both influenza and SARS-CoV-2 simultaneously using either:
- Multiplex PCR assays that detect both pathogens in a single sample 2
- Separate rapid tests for each pathogen
- Do not stop at influenza diagnosis if symptoms include fever, myalgia, weakness, shortness of breath, and cough 2
- IDSA guidelines recommend NAAT testing for symptomatic individuals with at least one common COVID-19 symptom 5
For asymptomatic exposed individuals:
- Test for SARS-CoV-2 at least 5 days after known exposure, regardless of influenza status 5
- Consider testing if results will impact isolation decisions or if the patient is high-risk (immunocompromised, pulmonary conditions) 5
Key Testing Considerations
Timing matters: Perform antigen tests within 5 days of symptom onset for optimal performance 6. If using NAAT, either rapid or laboratory-based testing is appropriate 5.
Specimen collection: For NAAT in symptomatic individuals, nasopharyngeal, anterior nasal, oropharyngeal, midturbinate swabs, saliva, or mouth gargle specimens are all acceptable 5.
If antigen test is negative but clinical suspicion remains high: Confirm with standard NAAT (rapid RT-PCR or laboratory-based NAAT) 6.
Common Pitfalls to Avoid
- Do not assume influenza explains all symptoms. The overlapping clinical presentations make differentiation impossible without testing both 7
- Do not rely on radiographic findings alone. While COVID-19 may show more bilateral ground-glass opacities with consolidation, this is not sufficiently specific 7
- Do not delay treatment decisions. Use rapid testing when available to enable same-encounter management decisions 5
The evidence strongly supports testing for both pathogens given the severe consequences of missed coinfection and the inability to clinically distinguish between single infection and coinfection 2, 1, 4.