Testing Guidance for Clinicians When SARS-CoV-2 and Influenza Viruses are Co-circulating

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

Patients with Acute Respiratory Illness Symptoms Requiring Hospital Admission (With or Without Fever)

  1. Specimen collection
  • Implement recommended infection prevention and control measures and collect respiratory specimens for influenza and SARS-CoV-2 testing.1  (Two different respiratory specimens may need to be collected if multiplex testing is unavailable).
  1. SARS-CoV-2 and Influenza Testing
  • Order multiplex nucleic acid detection assay for influenza A/B/SARS-CoV-2.2,3  If not available, order SARS-CoV-2 nucleic acid detection assay3 and influenza nucleic acid detection assay4  (If a SARS-CoV-2 nucleic acid detection assay is not available on-site and a SARS-CoV-2 antigen detection assay is used,5 confirm negative SARS-CoV-2 antigen detection assay results by SARS-CoV-2 nucleic acid detection assay at an outside laboratory). (Note: Rapid influenza antigen detection assays are not recommended due to lower sensitivities compared with rapid influenza nucleic acid detection assays.)

(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 COVID-19, and a positive SARS-CoV-2 test result without influenza testing does not exclude influenza.)

  • In critically ill intubated and mechanically ventilated patients who are suspected to have COVID-19 or influenza without a confirmed diagnosis, including when upper respiratory tract specimens are negative, lower respiratory tract (e.g. endotracheal aspirate) specimens should be collected for SARS-CoV-2 and influenza virus testing by nucleic acid detection assay per NIH COVID-19 Treatment Guidelines,6 and Infectious Diseases Society of America Influenza Clinical Practice Guidelines.7
  1. Treatment
  • If bacterial pneumonia or sepsis is suspected, consider testing recommendations and empiric antibiotic treatment per American Thoracic Society-Infectious Diseases Society of America Adult Community-acquired Pneumonia Guidelines,8 and administer supportive care and treatment for suspected or confirmed COVID-19 patients per NIH COVID-19 Treatment Guidelines.6 (Note: community-acquired bacterial co-infections can occur with COVID-19 but appear to be uncommon,9,10,11 and may be more common with influenza.7)
  • Start empiric oseltamivir treatment for suspected influenza as soon as possible regardless of illness duration, without waiting for influenza testing results, per Infectious Diseases Society of America Influenza Clinical Practice Guidelines,7,12 and administer supportive care.


  1. Implement recommended infection prevention and control measures; including while collecting respiratory specimens. Check the manufacturer’s package insert for approved respiratory specimens. Note: there are no FDA-cleared influenza diagnostic assays that utilize saliva specimens.
  2. CDC. Multiplex Assays Authorized for Simultaneous Detection of Influenza Viruses and SARS-CoV-2 by FDA Emergency Use Authorization.
  3. FDA. Individual EUAs for Molecular Diagnostic Tests for SARS-CoV-2external icon.
  4. CDC. FDA-cleared Nucleic Acid Detection Based Tests for Influenza Viruses.
  5. FDA. Individual EUAs for Antigen Diagnostic Tests for SARS-CoV-2external icon. Note: Because antigen detection assays have lower sensitivity than nucleic acid detection assays, a negative result does not necessarily exclude SARS-CoV-2 infection and should be confirmed by nucleic acid detection assay.
  6. NIH Coronavirus Disease 2019 (COVID-19) Treatment Guidelinesexternal icon.
  7. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaexternal icon.
  8. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of Americaexternal icon.
  9. Langford BJ, So M, Raybardhan S, Leung V, Westwood D, MacFadden DR, Soucy JR, Daneman N. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clin Microbiol Infect. 2020 Jul 22:S1198-743X(20)30423-7. doi: 10.1016/j.cmi.2020.07.016. Online ahead of print.
  10. Adler H, Ball R, Fisher M, Mortimer K, Vardhan MS. Low rate of bacterial co-infection in patients with COVID-19. Lancet Microbe. 2020 Jun;1(2):e62. doi: 10.1016/S2666-5247(20)30036-7. Epub 2020 Jun 8.
  11. Vaughn VM, Gandhi T, Petty LA, Patel PK, Prescott HC, Malani AN, Ratz D, McLaughlin E, Chopra V, Flanders SA. Empiric Antibacterial Therapy and Community-onset Bacterial Co-infection in Patients Hospitalized with COVID-19: A Multi-Hospital Cohort Study. Clin Infect Dis. 2020 Aug 21:ciaa1239. doi: 10.1093/cid/ciaa1239. Online ahead of print.
  12. CDC. Influenza Antiviral Medications: Summary for Clinicians.