Early Corticosteroids in Severe Influenza Pneumonia

Influenza virus infections cause excessive hospitalizations and deaths during seasonal peaks and pandemics. It remains a leading cause of admission to intensive care units (ICU) for acute respiratory failure. Apart from annual vaccination and other preventive measures, early administration of neuraminidase inhibitors is the only recommended treatment, but with a low level of evidence. Corticosteroids attenuate the immune response to infection and improve outcomes in patients with several types of severe pulmonary infections. Low-dose corticosteroids have been shown to reduce mortality in patients with severe COVID-19 and communityacquired pneumonia. It may also benefit critically ill patients with acute respiratory distress syndrome by reducing mortality, duration of mechanical ventilation and length of hospital stay. Observational studies with a high risk of bias have suggested an increase in mortality in patients with influenza who receive corticosteroid therapy. Others have shown a beneficial effect of corticosteroids or no link between their use and mortality. One concern for clinicians is the risk of Influenza-associated pulmonary aspergillosis (IAPA), which affects 10-20% of patients and is associated with a poor prognosis. However, there is insufficient evidence on the effects of corticosteroids administered during the ICU stay. Based on these findings and in the absence of a randomized trial, current guidelines do not recommend corticosteroid therapy in severe influenza. Therefore, a wellpowered trial is needed to test the hypothesis that corticosteroids could improve outcomes in critically-ill patients with severe influenza and acute respiratory failure.

Inclusion criteria

• Age ≥ 18 y
• Admission to ICU or intermediate care for less than 2 days
• Admission to hospital for less than 5 days
• Diagnosis of influenza pneumonia with

• PCR positive for Influenza dated less than 5 days
• AND focal shadowing/infiltrates on chest X-ray or CT-scan
• AND at least one of the following: cough, purulent sputum, chest pain or dyspnoea
• Requirement of supplemental oxygen at a flow rate of at least 3L/min OR non-invasive ventilation OR high flow oxygen therapy OR invasive mechanical ventilation
• Written informed or emergency consent
• Ongoing medical insurance

Exclusion criteria

• Moribund state
• Bone marrow transplant or chemotherapy-induced neutropenia
• Known allergy to dexamethasone or to one of its excipients
• Uncontrolled psychotic states
• Pheochromocytoma
• Co-infection with COVID-19
• Cardiogenic shock secondary to influenza myocarditis
• Known active tuberculosis or fungal infection
• Active viral hepatitis or active herpes virus infection
• Patient at risk of strongyloidiasis
• Subject with shock on enrolment and on ongoing vasopressor therapy (≥ 0.25 microg/kg/min)
• Indication for corticosteroid therapy in a dosage above 0.5mg/kg/day prednisone-equivalent
• Subject deprived of liberty or under a legal protective measure (example: patients under guardianship or curatorship)
• Pregnant or breastfeeding woman
• Lack of clinical equipoise by the attending physician and/or the presence of a substantial risk associated with the patients' participation in the trial