Steroid Treatment for Severe Acute Respiratory Infection (STAR) Trial

Inclusion Criteria: * Age ≥ 18 years. * Severe acute respiratory infection (SARI), defined as a suspected infection of the respiratory tract that meets each of the following 4 criteria: 1. Onset in the last 10 days AND 2. Results in hospitalization AND 3. At least one symptom or sign of respiratory illness (defined as purulent sputum, new or worsened cough, new or worsened dyspnea, tachypnea with respiratory rate ≥22 breaths per minute, rales, or bronchial breath sounds) AND 4. At least one symptom or sign of acute infection (defined as a temperature ≥38°C or ≤36°C, feverishness, chills, altered mental status, a white blood cell count of \>12,000/mm3, \<4,000/mm3, or \>10% immature neutrophils, or imaging findings consistent with acute respiratory infection). * Hypoxemia, defined as meeting one or more of the following at the time of eligibility assessment: 1. An oxygen saturation \<92% in a patient who does not receive chronic supplemental oxygen OR 2. Receipt of ≥3 liters per minute of supplemental oxygen or a fraction of inspired oxygen of ≥0.35 in a patient who does not receive chronic supplemental oxygen OR 3. Receipt of a flow rate of supplemental oxygen ≥3 liters per minute greater than pre-illness baseline or a fraction of inspired oxygen ≥0.10 greater than pre-illness baseline in a patient who receives chronic supplemental oxygen. Exclusion Criteria: * Hospitalized for \>72 hours * Primary etiology of hypoxemia is a condition other than respiratory infection * Known allergy or adverse reaction to systemic corticosteroids * Known active infection with SARS-CoV-2, known active infection with Pneumocystis jirovecii, or another established indication for systemic corticosteroids * Known active disseminated or pulmonary infection with Mycobacterium tuberculosis, Aspergillus, Blastomyces, Coccidioides, Cryptococcus, Histoplasma, or Strongyloides species; active systemic infection with herpes simplex virus, varicella zoster virus, or cytomegalovirus; or another established contraindication to systemic corticosteroids * Prisoner * Treatment is prioritizing end-of-life symptom management over prolongation of life * Investigator determines that participation in the trial is not in the patient's best interest * Receipt of greater than 14 days of systemic corticosteroids at a dose equivalent to greater than 10 mg of prednisolone per day in the 30 days prior to hospital presentation (i.e., chronic corticosteroids) * Receipt of systemic corticosteroids at a dose equivalent to greater than 30 mg of prednisolone per day on 2 or more calendar days since hospital presentation * Clinicians determine that the administration of systemic corticosteroids at a dose equivalent to greater than 10 mg of prednisolone per day is required, or is likely to be required in the next 24 hours, for the optimal care of the patient (such as for acute exacerbation of chronic obstructive pulmonary disease, adrenal insufficiency, asthma, continuation of chronic corticosteroid therapy, or severe shock) * Clinicians determine that the administration of systemic corticosteroids is not consistent with the optimal care of the patient (such as for recent peptic ulcer disease, recent gastrointestinal bleeding, severe burns, severe delirium, severe hyperglycemia or diabetic ketoacidosis, or severe hypertension) * Patient (or surrogate decision-maker / legally authorized representative) declines to provide informed consent to participate