Clinical Guidance for Patients with Acute Respiratory Illness 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]

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.2-4)
  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 or antigen detection assay and influenza nucleic acid detection assay.4
    • (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, especially if 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. 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, and may result in severe disease,5-7 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,8 and Infectious Diseases Society of America Influenza Clinical Practice Guidelines.9
  1. RSV testing
  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,10 and administer supportive care and treatment for suspected or confirmed COVID-19 patients per NIH COVID-19 Treatment Guidelines.8
    • (Note: community-acquired bacterial co-infections can occur with COVID-19 but appear to be uncommon,11-13 and more common with influenza.9)
  • 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,9,14 and administer supportive care.
  1. Reminder: 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. 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-2.
  4. FDA-cleared Nucleic Acid Detection Based Tests for Influenza Viruses.
  5. Stowe J, Tessier E, Zhao H, Guy R, Muller-Pebody B, Zambon M et al. Interactions between SARS-CoV-2 and influenza, and the impact of coinfection on disease severity: a test-negative design. Int J Epidemiol. 2021 Aug 30;50(4):1124-1133. doi: 10.1093/ije/dyab081.
  6. Swets MC, Russell CD, Harrison EM, Docherty AB, Lone N, Girvan M et al. SARS-CoV-2 co-infection with influenza viruses, respiratory syncytial virus, or adenoviruses. Lancet. 2022 Apr 16;399(10334):1463-1464. doi: 10.1016/S0140-6736(22)00383-X.
  7. Adams K, Tastad KJ, Huang S, Ujamaa D, Kniss K, Cummings C et al. Prevalence of SARS-CoV-2 and Influenza Coinfection and Clinical Characteristics Among Children and Adolescents Aged <18 Years Who Were Hospitalized or Died with Influenza – United States, 2021-22 Influenza Season. MMWR Morb Mortal Wkly Rep. 2022 Dec 16;71(50):1589-1596. doi: 10.15585/mmwr.mm7150a4.
  8. NIH Coronavirus Disease 2019 (COVID-19) Treatment Guidelines Panel.
  9. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza.
  10. 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.
  11. Langford BJ, So M, Raybardhan S, Leung V, Westwood D, MacFadden DR, et al. 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.
  12. 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.
  13. 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.
  14. Influenza Antiviral Medications: Summary for Clinicians.