Each year, influenza A infection caused great mortality and morbidity, especially among the elderly and individuals with chronic illness. Many of these patients are 'late presenters' who are admitted to hospital a few days after symptoms onset and have developed complications secondary to immunodysregulation. Antiviral treatment with the neuraminidase inhibitor is of limited usage for patients who presented to the hospital 48 hours after symptom onset. Apart from ventilatory and extracorporeal membrane oxygenation support, treatment options for these patients are limited. Recent animal study has demonstrated that combinations of an antiviral agent with a COX-II inhibitor can reduce mortality in mice infected with influenza virus. The investigators therefore propose to enrol patients with severe influenza A infection requiring hospitalization and oxygen support on a randomized controlled trial with celecoxib.

The aim of this double blind randomized controlled trial is to compare the clinical efficacy and safety of celecoxib combined with neuraminidase inhibitors in patients with severe influenza A infection. The hypothesis of this study is that treatment of severe influenza A infection with celecoxib will reduce mortality. The primary outcome to be assessed will be the 28-days mortality rate from hospitalization. The secondary outcomes to be assessed will be safety of the treatment, duration of intensive care, duration of ventilatory and oxygen support, the viral load and cytokine change.

Inclusion Criteria:

1) Male or female patients ≥18 years 2) Written informed consent by patient or next-of kin (if patient is too ill to consent) 3) Presumptive diagnosis of influenza A satisfying both clinical and laboratory criteria. The laboratory criteria are defined as at least one RT-PCR positive for influenza A (H1N1, H3N2, H5N1 and H7N9) from respiratory clinical specimens including nasopharyngeal samples and endotracheal aspirates. The clinical criteria are defined as hospitalization with fever or one of the symptoms suggestive of influenza infection including sore throat, rhinorrhea, cough or shortness of breath 2) Desaturation to <90% in room air by pulse oximetry and required oxygen supplement 3) Within 7 days of onset of symptoms. Patients have to fulfil all the aforementioned criteria.

Exclusion Criteria:

1) Age <18 years. 2) A known hypersensitivity to celecoxib, oseltamivir or zanamivir 3) Unable to obtain informed consents 4) Influenza A infection diagnosed beyond 7 days from symptom onset 5) Patients receiving other antiviral treatment (apart from oseltamivir or zanamivir), N-acetylcystiene, statins and tradition Chinese medicine during the current admission 6) Patients with renal impairment of creatinine clearance < 30mL/min