Influenza and COVID-19
Last Updated: October 22, 2020
Diagnosis of Influenza and COVID-19 When Influenza Viruses and SARS-CoV-2 Are Cocirculating
Antiviral Treatment of Influenza When Influenza Viruses and SARS-CoV-2 Are Cocirculating
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials without major limitations; IIa = Other randomized trials or subgroup analyses of randomized trials; IIb = Nonrandomized trials or observational cohort studies; III = Expert opinion
Influenza activity in the United States during the 2020–2021 influenza season is difficult to predict and could vary geographically and by the extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community mitigation measures. During early 2020, sharp declines in influenza activity coincided with implementation of SARS-CoV-2 control measures in the United States and several Asian countries.1-4 Very low influenza virus circulation was observed in Australia, Chile, and South Africa during the typical Southern Hemisphere influenza season in 2020.5 Clinicians should monitor local influenza and SARS-CoV-2 activity (e.g., by tracking local and state public health surveillance data and testing performed at health care facilities) to inform evaluation and management of patients with acute respiratory illness.
There are no data on the safety, immunogenicity, or effectiveness of influenza vaccines in patients with mild COVID-19 or those who are recovering from COVID-19. Therefore, the optimal timing for influenza vaccination in these patients is unknown. The safety and efficacy of vaccinating persons who have mild illnesses from other etiologies have been documented.6 On the basis of practice following other acute respiratory infections, the Panel recommends that persons with COVID-19 should receive an inactivated influenza vaccine (BIII). The Centers for Disease Control and Prevention (CDC) has provided guidance on the timing of influenza vaccination for inpatients and outpatients with COVID-19 (see Interim Guidance for Routine and Influenza Immunization Services During the COVID-19 Pandemic). It is not known whether dexamethasone or other immunomodulatory therapies for COVID-19 will affect the immune response to influenza vaccine. However, despite this uncertainty, as long as influenza viruses are circulating, an unvaccinated person with COVID-19 should receive the influenza vaccine once they have substantially improved or recovered from COVID-19. See influenza vaccine recommendations from CDC and the Advisory Committee on Immunization Practices.
Clinical Presentation of Influenza Versus COVID-19
The signs and symptoms of uncomplicated, clinically mild influenza overlap with those of mild COVID-19. Ageusia and anosmia can occur with both diseases, but these symptoms are more common with COVID-19 than with influenza. Fever is not always present in patients with either disease, particularly in patients who are immunosuppressed or elderly. Complications of influenza and COVID-19 can be similar, but the onset of influenza complications and severe disease typically occurs within a week of illness onset whereas the onset of severe COVID-19 usually occurs in the second week of illness. Because of the overlap in signs and symptoms, when SARS-CoV-2 and influenza viruses are cocirculating, diagnostic testing for both viruses in people with an acute respiratory illness is needed to distinguish between SARS-CoV-2 and influenza virus, and to identify SARS-CoV-2 and influenza virus coinfection. Coinfection with influenza A or B viruses and SARS-CoV-2 has been described in case reports and case series,7-11 but the frequency, severity, and risk factors for coinfection with these viruses versus for infection with either virus alone are unknown.
Which Patients Should be Tested for SARS-CoV-2 and influenza?
When influenza viruses and SARS-CoV-2 are cocirculating in the community, SARS-CoV-2 testing and influenza testing should be performed in all patients hospitalized with suspected COVID-19 or influenza (see Testing for SARS-CoV-2 Infection) (AIII). When influenza viruses and SARS-CoV-2 are cocirculating in the community, SARS-CoV-2 testing should be performed in outpatients with suspected COVID-19, and influenza testing can be considered in outpatients with suspected influenza if the results will change clinical management of the illness (BIII). Several multiplex assays that detect SARS-CoV-2 and influenza A and B viruses have received Food and Drug Administration Emergency Use Authorization and can provide results in 15 minutes to 8 hours on a single respiratory specimen.12,13 For information on available influenza tests, including clinical algorithms for testing of patients when SARS-CoV-2 and influenza viruses are cocirculating, see the CDC Information for Clinicians on Influenza Virus Testing and recommendations of the Infectious Diseases Society of America (IDSA) on the use of influenza tests and interpretation of testing results.14
Which Patients Should Receive Antiviral Treatment of Influenza?
When SARS-CoV-2 and influenza viruses are cocirculating in the community, patients who require hospitalization and are suspected of having either or both viral infections should receive influenza antiviral treatment with oseltamivir as soon as possible without waiting for influenza testing results (AIIb).14 Treatment for influenza is the same for all patients regardless of SARS-CoV-2 coinfection (AIII). See the CDC Influenza Antiviral Medications: Summary for Clinicians, including clinical algorithms for antiviral treatment of patients with suspected or confirmed influenza when SARS-CoV-2 and influenza viruses are cocirculating, and the IDSA Clinical Practice Guidelines recommendations on antiviral treatment of influenza.
If a diagnosis of COVID-19 or another etiology is confirmed and if the result of an influenza nucleic acid detection assay from an upper respiratory tract specimen is negative:
- In a Patient Who is Not Intubated: Antiviral treatment for influenza can be stopped.
- In a Patient Who is Intubated: Antiviral treatment for influenza should be continued and if a lower respiratory tract specimen (e.g., endotracheal aspirate) can be safely obtained, it should be tested by influenza nucleic acid detection. If the lower respiratory tract specimen is also negative, influenza antiviral treatment can be stopped.
Treatment Considerations for Hospitalized Patients With Suspected or Confirmed SARS-CoV-2 and Influenza Virus Coinfection
- Corticosteroids, which may be used for the treatment of COVID-19, may prolong influenza viral replication and viral RNA detection and may be associated with poor outcomes.14,15
- Oseltamivir has no activity against SARS-CoV-2.16 Oseltamivir does not have any known interactions with remdesivir.
- Standard-dose oseltamivir is well absorbed even in critically ill patients. For patients who cannot tolerate oral or enterically administered oseltamivir (e.g., because of gastric stasis, malabsorption, or gastrointestinal bleeding), intravenous peramivir is an option.14 There are no data on peramivir activity against SARS-CoV-2.
- CDC does not recommend inhaled zanamivir and oral baloxavir for the treatment of influenza in hospitalized patients because of insufficient safety and efficacy data (see the CDC Influenza Antiviral Medications: Summary for Clinicians). There are no data on zanamivir activity against SARS-CoV-2. Baloxavir has no activity against SARS-CoV-2.16
- Based upon limited data, the co-occurrence of community-acquired secondary bacterial pneumonia with COVID-19 appears to be infrequent and may be more common with influenza.17,18 Typical bacterial causes of community-acquired pneumonia with severe influenza are Staphylococcus aureus (methicillin-resistant S. aureus [MRSA] and methicillin-susceptible S. aureus [MSSA]), Streptococcus pneumoniae, and group A Streptococcus.14
- Patients with COVID-19 who develop new respiratory symptoms with or without fever or respiratory distress, and without a clear diagnosis, should be evaluated for the possibility of nosocomial influenza.
- Kuo SC, Shih SM, Chien LH, Hsiung CA. Collateral benefit of COVID-19 control measures on influenza activity, Taiwan. Emerg Infect Dis. 2020;26(8):1928-1930. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32339091.
- Soo RJJ, Chiew CJ, Ma S, Pung R, Lee V. Decreased influenza incidence under COVID-19 control measures, Singapore. Emerg Infect Dis. 2020;26(8):1933-1935. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32339092.
- Suntronwong N, Thongpan I, Chuchaona W, et al. Impact of COVID-19 public health interventions on influenza incidence in Thailand. Pathog Glob Health. 2020;114(5):225-227. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32521210.
- Lei H, Xu M, Wang X, et al. Non-pharmaceutical interventions used to control COVID-19 reduced seasonal influenza transmission in China. J Infect Dis. 2020; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32898256.
- Olsen SJ, Azziz-Baumgartner E, Budd AP, et al. Decreased influenza activity during the COVID-19 pandemic—United States, Australia, Chile, and South Africa, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(37):1305-1309. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32941415.
- Centers for Disease Control and Prevention. Contraindications and precautions. General best practice guidelines for immunization: best practices guidance of the advisory committee on immunization practices (ACIP). 2020. Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/contraindications.html. Accessed October 16, 2020.
- Hashemi SA, Safamanesh S, Ghasemzadeh-Moghaddam H, Ghafouri M, Azimian A. High prevalence of SARS-CoV-2 and influenza A virus (H1N1) coinfection in dead patients in Northeastern Iran. J Med Virol. 2020; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32720703.
- Huang BR, Lin YL, Wan CK, et al. Co-infection of influenza B virus and SARS-CoV-2: A case report from Taiwan. J Microbiol Immunol Infect. 2020; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32646801.
- Yue H, Zhang M, Xing L, et al. The epidemiology and clinical characteristics of co-infection of SARS-CoV-2 and influenza viruses in patients during COVID-19 outbreak. J Med Virol. 2020; Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32530499.
- Cuadrado-Payan E, Montagud-Marrahi E, Torres-Elorza M, et al. SARS-CoV-2 and influenza virus co-infection. Lancet. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32423586.
- Wu X, Cai Y, Huang X, et al. Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. Emerg Infect Dis. 2020;26(6):1324-1326. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32160148.
- Food and Drug Administration. Coronavirus disease 2019 (COVID-19) emergency use authorizations for medical devices. Individual EUAs for molecular diagnostic tests for SARS-CoV-2. 2020. Available at: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/vitro-diagnostics-euas#individual-molecular. Accessed October 16, 2020.
- Centers for Disease Control and Prevention. Table 4. Multiplex assays authorized for simultaneous detection of influenza viruses and SARS-CoV-2 by FDA. 2020. Available at: https://www.cdc.gov/flu/professionals/diagnosis/table-flu-covid19-detection.html. Accessed October 16, 2020.
- Uyeki TM, Bernstein HH, Bradley JS, et al. Clinical practice guidelines by the Infectious Diseases Society of America: 2018 update on diagnosis, treatment, chemoprophylaxis, and institutional outbreak management of seasonal influenza. Clin Infect Dis. 2019;68(6):e1-e47. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30566567.
- Zhou Y, Fu X, Liu X, et al. Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis. Sci Rep. 2020;10(1):3044. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32080223.
- Choy KT, Wong AY, Kaewpreedee P, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32251767.
- Vaughn VM, Gandhi T, Petty LA, et al. Empiric antibacterial therapy and community-onset bacterial co-infection in patients hospitalized with COVID-19: a multi-hospital cohort study. Clin Infect Dis. 2020; published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32820807.
- Adler H, Ball R, Fisher M, Mortimer K, Vardhan MS. Low rate of bacterial co-infection in patients with COVID-19. Lancet Microbe. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32835331.