Adaptive RCT of Corticosteroids for Severe Influenza Pneumonia in Adults

Inclusion criteria

• Age ≥ 18 years.
• Admission to the Intensive Care Unit (ICU).
• Meeting the diagnostic criteria for community-acquired pneumonia (CAP).
• Meeting at least one of the major diagnostic criteria for severe pneumonia:

(i) Requirement for endotracheal intubation and mechanical ventilation;

(ii) Septic shock requiring vasopressor therapy after adequate fluid resuscitation.

-Or simultaneously fulfilling three of the minor criteria:

(i) Respiratory rate ≥ 30 breaths/min;

(ii) PaO₂/FiO₂ ≤ 250 mmHg;

(iii) Multilobar infiltrates;

(iv) Altered mental status and/or disorientation;

(v) Blood urea nitrogen ≥ 20 mg/dL (7.12 mmol/L);

(vi) Leukopenia (white blood cell count < 4 × 10⁹/L);

(vii) Thrombocytopenia (platelet count < 100 × 10⁹/L);

(viii) Hypothermia (core temperature < 36 °C);

(ix) Hypotension (systolic blood pressure < 90 mmHg) requiring aggressive fluid resuscitation.

• Confirmed influenza virus etiology: at least one positive nucleic acid test (RT-PCR/PCR) or next-generation sequencing (NGS) result for influenza virus in respiratory specimens (respiratory secretions, throat swabs, or bronchoalveolar lavage fluid).
• Severe community-acquired pneumonia (SCAP) patients admitted to the emergency department/ward/ICU due to respiratory failure within < 72 hours.
• Signed informed consent.

Exclusion criteria

• Patients receiving vasopressor therapy for septic shock at the time of enrollment.
• Terminally ill patients (expected survival <30 days, e.g., advanced malignancy).
• Clinical history suggesting overt aspiration.
• Documented active gastrointestinal bleeding.
• Presence of cystic fibrosis, obstructive pneumonia, active influenza, pulmonary tuberculosis, or fungal infection.
• Active viral hepatitis or active herpesvirus infection.
• Bone marrow suppression or HIV infection.
• Refusal of mechanical ventilation and endotracheal intubation.
• Uncontrolled hyperglycemia (diabetic ketoacidosis with blood ketones >3 mmol/L, or hyperosmolar hyperglycemic state with blood glucose >33.3 mmol/L and elevated osmolality).
• Known allergy to corticosteroids.
• Patients requiring anti-inflammatory corticosteroids or replacement hydrocortisone for any reason, or those already receiving prednisone >15 mg/day (or equivalent dose of another corticosteroid).
• Pregnant or breastfeeding women.