Early administration of oseltamivir to patients with influenza type A/H3N2 (RR=0.69, 95% CI: 0.49-0.94) significantly reduces the overall flu-associated mortality, was found in a study conducted over eight winter seasons in Greece from 2010-2011 to 2017-2018. Oseltamivir was predominantly effective in A/H3N2 rather in A/H1N1 or B. These findings were published in Clinical Infectious Diseases.1
Influenza viruses circulate around the world each year, causing infections and diseases in all age groups.2 A small fraction of influenza virus infections are severe, requiring hospitalization, whereas some infections can be fatal.2 Apart from deaths caused by primary viral pneumonia, influenza viral infections can lead to secondary bacterial infections and exacerbate underlying medical conditions such as cardiovascular disease.2 Each year in Hong Kong, an average of 12,700 respiratory hospitalizations and 431 respiratory deaths are attributable to influenza. The impact varies from year to year depending on the circulating strains.3 However, influenza A (H3N2) epidemics tend to have the highest impact in older adults.3 The neuraminidase inhibitors (NAIs), of which oseltamivir is the most frequently prescribed, are the only currently available antiviral medications to treat influenza.4 The mechanism of action of oseltamivir is to inhibit viral NAIs and viral replication, through which it facilitates viral clearance and quicker recovery.5 The early use of NAIs, preferably within first 48 hours, is recommended for patients with severe illness or high risk complications.4
Dr. Theodore Lytras, MD, at the Hellenic Centres for Disease Control and Prevention, Athens, and colleagues examined data from an active surveillance system for severe influenza in Greece.1 The study included 1,330 severely ill, ICU-hospitalized patients (ages ≥18) with laboratory-confirmed influenza. Patients were treated at ICU, mechanically ventilated, and received oseltamivir alone.1 The primary outcome was considered as the death in the ICU versus recovered discharge from the ICU.1 Among the study population, slightly over half of the patients had influenza A/H1N1, while the rest had influenza A/H3N2 or influenza B.1
There were 622 deaths (46.8%) in the ICU out of 1,330 patients, with no significant difference between the early or late administration of oseltamivir, except in A/H3N2 patients.1 Accordingly, they found that fewer patients with influenza A/H3N2 died in the early group versus the late group (33.7% vs. 48.4%, p=0.029). In addition, the median length of stay in the ICU was shorter in the early group versus the late group (12 days vs. 15 days, p=0.003).1
The authors have identified the decrease of 30% in mortality among the A/H3N2 patients as “especially significant”. They further stated “This subtype is often poorly covered by the seasonal influenza vaccine, and frequently affects elderly patients causing significant morbidity and mortality.”1 The decrease in mortality among these critically ill patients by oseltamivir emphasizes its potential for the prevention of influenza related death.1
On the other hand, no mortality benefits were observed from the early administration of oseltamivir in influenza B or A/H1N1.1 This suggests that the action of oseltamivir varies between different influenza types, which could be due to host factors or differences in the structure and activity of viral NAIs.6 Therefore, assumptions should not be made that drugs with the same biological functions could affect all the influenza strains equally. The authors have stated that more research is needed in the area to determine the strain specific antiviral agents.
According to the authors, the study had some limitations, including its observational nature, making it potentially subject to other confounding factors.1 Furthermore, the dosage or duration of oseltamivir was not consistently recorded in the data base and the safety outcomes were also not measured.1
In conclusion, early oseltamivir decreased the mortality among patients infected with the A/H3N2 influenza by 30% and shortened the hospital stay to 12 days versus 15 days. However, the mortality benefit of early oseltamivir for influenza A/H3N2 or influenza B was not significant.
1. Lytras T, Mouratidou E, Andreopoulou A, et al. Effect of early oseltamivir treatment on mortality in critically ill patients with different types of influenza: a multi-season cohort study. Clin Infect Dis. 2019. 10.1093/cid/ciz101
2. Kuiken T, Taubenberger JK. Pathology of human influenza revisited. Vaccine. 2008;26(Suppl 4):D59-66.
3. Wu P, Presanis AM, Bond HS, et al. A joint analysis of influenza-associated hospitalizations and mortality in Hong Kong, 1998-2013. Sci Rep. 2017;7(1):929-932.
4. 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 Influenzaa. Clin Infect Dis. 2019;68(6):895-902.
5. Lee N, Ison MG. Inhibiting Viral Polymerase and Neuraminidase in Treating Influenza. J Infect Dis. 2019;219(7):1013-5.
6. Burnham AJ, Baranovich T, Govorkova EA. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance. Antiviral Res. 2013;100(2):520-34.