Clinical Guidance for Patients with Acute Respiratory Illness Not Being Hospitalized When SARS-CoV-2 and Influenza Viruses are Co-Circulating

[Based upon local public health surveillance data and testing at local healthcare facilities]

Outpatient Clinic or Emergency Department Patients with Acute Respiratory Illness Symptoms (With or Without Fever) Not Requiring Hospital Admission

  1. Specimen Collection
  • Implement recommended infection prevention and control measures and collect respiratory specimens as indicated for influenza and SARS-CoV-2 testing.1 (Two different specimens may need to be collected if multiplex testing for influenza viruses and SARS-CoV-2 is unavailable on-site.2-4)
  1. SARS-CoV-2 Testing
  • Test for SARS-CoV-2 by nucleic acid detection3 OR SARS-CoV-2 antigen detection assay,4 especially in persons at increased risk for progression to severe COVID-19.5 (Note: Because antigen detection assays have lower sensitivity than nucleic acid detection assays, a negative SARS-CoV-2 antigen detection assay result does not necessarily exclude SARS-CoV-2 infection and should be confirmed by SARS-CoV-2 nucleic acid detection assay or repeat antigen testing 48 hours later, if clinical suspicion for COVID-19 is high – such as in the setting of high SARS-CoV-2 community prevalence or recent close exposure to a person with COVID-19.) If the second antigen test is negative, per FDA guidance, a third antigen test could be considered if there is a high clinical suspicion of COVID-19.
  1. Influenza Testing
  • Test for influenza if results will change clinical management or for infection control decisions (e.g. long-term care facility resident returning to a facility, or a person of any age returning to a congregate setting): order rapid influenza nucleic acid detection assay;6,7 if rapid influenza nucleic acid detection assay is not available on-site, order rapid influenza antigen detection assay.8 (If available, multiplex nucleic acid detection assay for SARS-CoV-2, influenza A and B viruses can be performed on-site, or at an offsite clinical laboratory.2,6)
    (Note: Because SARS-CoV-2 and influenza virus co-infection can occur, a positive influenza test result without SARS-CoV-2 testing does not exclude SARS-CoV-2 infection, and a positive SARS-CoV-2 test result without influenza testing does not exclude influenza virus infection).
  1. Treatment
  • If a SARS-CoV-2 test result is positive, administer supportive care. If the patient is at high risk for progression to severe COVID-19, prescribe treatment for nonhospitalized patients as recommended per NIH COVID-19 Treatment Guidelines.9
  • Prescribe influenza antiviral treatment if on-site influenza testing is positive OR prescribe empiric antiviral treatment without influenza testing based upon a clinical diagnosis of influenza for patients of any age with progressive disease of any duration, and for children and adults at high risk for influenza complications with illness.5,7,10 Encourage patients to start antiviral treatment as soon as possible.
  • For adult patients with suspected community-acquired pneumonia who do not require hospitalization, see antibiotic treatment recommendations from the American Thoracic Society-Infectious Diseases Society of America Adult Community-acquired Pneumonia Guidelines.11
  • For otherwise healthy non-high-risk persons with influenza-like illness (fever and either cough or sore throat) with illness ≤2 days, empiric antiviral treatment of suspected influenza can be prescribed based upon clinical judgement.7,10
  • For otherwise healthy non-high-risk persons without influenza-like illness or with illness duration >2 days, antiviral treatment of influenza is unlikely to provide significant clinical benefit.7
  1. Follow isolation and quarantine recommendations for SARS-CoV-2,12 and arrange follow-up for any pending testing results.
  1. Vaccination at discharge


  1. Implement recommended infection prevention and control measures for SARS-CoV-2; including while collecting respiratory specimens for SARS-CoV-2 and for influenza virus testing. Check the manufacturer’s package insert for approved respiratory specimens. Note: there are no FDA-cleared influenza diagnostic assays that utilize saliva specimens.
  2. Multiplex Assays Authorized for Simultaneous Detection of Influenza Viruses and SARS-CoV-2 by FDA Emergency Use Authorization.
  3. Individual EUAs for Molecular Diagnostic Tests for SARS-CoV-2.
  4. Individual EUAs for Antigen Diagnostic Tests for SARS-CoV-2.
  5. People at Higher Risk of Flu Complications.
  6. FDA-cleared Nucleic Acid Detection Based Tests for Influenza Viruses.
  7. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza.
  8. Available FDA-Cleared Rapid Influenza Diagnostic Tests (Antigen Detection Only). Note: Because rapid influenza antigen detection assays have lower sensitivity than influenza nucleic acid detection assays, a negative result does not necessarily exclude influenza virus infection, particularly when local influenza activity is high.
  9. NIH Coronavirus Disease 2019 (COVID-19) Treatment Guidelines.
  10. Influenza Antiviral Medications: Summary for Clinicians.
  11. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America.
  12. Ending Isolation and Precautions for People with COVID-19: Interim Guidance