Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection

Inclusion Criteria: 1. Admitted to participating hospital with symptoms suggestive of COVID-19 infection OR develop symptoms of COVID-19 during hospitalization 2. Subject (or legally authorized representative) can provide written informed consent (in English or Spanish) affirming intention to comply with planned study procedures prior to enrollment 3. Male or female adult aged 12 years or older at the time of enrollment 4. Has laboratory-confirmed SARS-CoV-2 infection determined by a validated nucleic acid amplification assay (public health or commercial) in any respiratory specimen collected within 14 days of randomization 5. Illness of any duration that includes * Radiographic evidence of pulmonary infiltrates (chest X-ray or CT scan) OR * Clinical documentation of lower respiratory symptoms (cough, shortness of breath, wheezing) OR * Any documented SpO2 ≤ 94% on room air OR * Any inpatient initiation or supplemental oxygen regardless of documented cause Exclusion Criteria: 1. Participating in any other clinical trial of an experimental agent for COVID-19 2. On hydroxychloroquine at any time during hospitalization, or within 180 days of hospitalization for COVID-19 regardless of indication 3. History of G6PD deficiency, cirrhosis, long QT syndrome or porphyria of any classification 4. Most recent ECG prior to time of screening with QTc of ≥500 msec 5. Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives 6. Death anticipated within 48 hours of enrollment 7. Inability to obtain informed consent from the patient or designated medical decision maker