The correct answer is:

Empiric treatment with oseltamivir for influenza should be started prior to influenza test results in all hospitalized patients with COVID-19 who come from a community with co-circulation of SARS-CoV-2 and influenza.

Key Point:

The NIH states the following with regards to empirical antiviral treatment for influenza when influenza viruses and SARS-CoV-2 are co-circulating:

• The treatment of influenza is unaffected by the presence/absence of SARS-CoV-2 coinfection (level AIII recommendation).
• In communities with co-circulation of influenza and SARS-CoV-2, hospitalized patients should be started on empiric treatment for influenza with oseltamivir as soon as possible without waiting for influenza testing results (level AII recommendation).
  • Antiviral treatment of influenza can be stopped when influenza has been ruled out by nucleic acid detection assay in upper respiratory tract specimens for nonintubated patients and in both upper and lower respiratory tract specimens for intubated patients.

Explanation:

When SARS-CoV-2 and influenza viruses are co-circulating in the community, patients who require hospitalization for an acute respiratory illness should receive influenza antiviral treatment with oseltamivir as soon as possible without waiting for influenza testing results. The usual influenza protocol does NOT need to be adjusted in patients infected with SARS-Co-V-2.

Co-occurrence of COVID-19 and influenza pneumonia in the same patient is more common than originally recognized. On the other hand, in patients with COVID-19, bacterial co-infection is less common than in patients with influenza (in whom bacterial superinfection is a well-recognized pulmonary complication). Recognizing co-infection with SARS-Co-V2 and influenza is important for multiple reasons. For example, 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.

Oseltamivir has no activity against SARS-CoV-2 and also 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.

The Centers of Disease Control and Prevention (CDC) do not recommend inhaled zanamivir and oral baloxavir for the treatment of influenza in hospitalized patients because of insufficient safety and efficacy data. In addition, there are no data on zanamivir activity against SARS-CoV-2. It is known that baloxavir has no activity against SARS-CoV-2.

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 co-circulating, and the IDSA Clinical Practice Guidelines recommendations on antiviral treatment of influenza.

References:

The National Institutes of Health COVID-19 Treatment Guidelines. (Updated December 17, 2020) (Accessed January 2, 2021).

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.

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.

Cuadrado-Payan E, Montagud-Marrahi E, Torres-Elorza M, et al. SARS-CoV-2 and influenza virus co-infection. Lancet. 2020.

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.

Choy KT, Wong AY, Kaewpreedee P, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020.