Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020

Abstract

Background Timely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients. Aim We assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20. Methods Case-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated. Results Of 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60–79 years aOR 3.0, 95% CI: 2.4–3.8; 80 years 8.3 (6.6–10.5)) and intensive care unit admission (3.8, 95% CI: 3.4–4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90–0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0–48 hours aOR 0.51, 95% CI: 0.45–0.59; 3–4 days 0.59 (0.51–0.67); 5–7 days 0.64 (0.56–0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40–59 years aOR 0.43, 95% CI: 0.28–0.66; 60–79 years 0.50 (0.39–0.63); ≥80 years 0.51 (0.42–0.63)). Conclusion NAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

Effectiveness of Influenza Vaccination and Early Antiviral Treatment in Reducing Pneumonia Risk in Severe Influenza Cases

“…Dominguez et al [ 23 ], in a study of 1727 hospitalized patients in Catalonia, reported a reduced mortality risk (aOR = 0.37; p < 0.001) for patients receiving NAI treatment in the first 48 h after clinical symptom onset. Similar results have been observed in a surveillance data survey conducted in 11 European countries [ 24 ]. Nonetheless, despite the evidence available on the effectiveness of antivirals in preventing severity, several barriers to their systematic use exist and clinical practice is quite variable [ 13 , 25 ].…”

“…Controlling for the effect of antiviral treatment, in our study, a history of vaccination was 15% effective in reducing the pneumonia risk in severe cases of influenza, a finding similar to that observed in other studies [20][21][22][23][24][25][26][27]. While this result may, on the face of it, seem to be less than spectacular, it needs to be considered in a context of pneumonia representing a greater risk of ICU admission and death for our patients, despite their relatively younger age and despite the greater severity profile for the control group due to higher rates of obesity, COPD, and ARDS.…”

“…Some patients may have been vaccinated in private centres and so their vaccination status was not in their medical records, although this is unlikely given that the Catalan vaccination programme is free and universal. Since symptom onset is difficult to determine in some patients, an inaccurate record may have delayed antiviral treatment, leading to an underestimation of pneumonia risk, as has been reported elsewhere [ 24 ]. While more influenza diagnostic tests may have been ordered for unvaccinated patients, this seems unlikely since healthcare providers were unaware of vaccination histories at the time of ordering the tests.…”