
    cohort 1: slow accrual cohort 2: other studies showed no benefit cohort 3: study met
    pre-specificied futility analysis at planned second interim analysis
  
['covid-19']
['hydroxychloroquine sulfate 400 mg twice a day', 'hydroxychloroquine sulfate 600 mg twice a day', 'hydroxychloroquine sulfate 600 mg once a day', 'placebo oral tablet']

        Inclusion Criteria:

          -  Age ≥ 18 years old (Sub-studies 2 and 3)

          -  Competent and capable to provide informed consent

          -  Have access to a smart device such as a cell phone, tablet, laptop computer with
             necessary data/internet accessibility

          -  Subjects meeting the following criteria by Sub-Study

        Sub-Study 1:

          -  Age ≥40 years since the risk of prolonged disease that progresses to severe COVID-19
             disease increases with age.

          -  PCR-positive for the SARS-CoV2 virus

          -  (Fever, and cough, or Fever and shortness of breath,

          -  ≤4 days since the first symptoms of COVID-19 and date of testing

          -  Not taking azithromycin

          -  Not requiring hospitalization and is sent home for quarantine.

          -  Must live within 30 miles of HUP or Penn Presbytarian Medical Center to facilitate
             drop-off of medication

          -  Must own a working computer, or smartphone and have internet access

          -  Must be willing to fill out a daily symptom diary

          -  Must be available for a daily phone call,

          -  Must take their own temperature twice a day

          -  Must be willing to report the observed symptoms and development of COVID-19 in the
             co-inhabitants of the residence at which the quarantine will be served.

        Sub-Study 2 Hospitalized non-ICU service patients.

          -  PCR-positive for SARS-CoV-2

          -  Patients admitted to a floor bed at Hospital of the University of Pennsylvania or Penn
             Presbyterian.

          -  One or more of the following risk factors for progression to severe disease including:
             immunocompromising conditions, structural lung disease, hypertension, coronary artery
             disease, diabetes, age > 60, ferritin > 850, CRP > 6, D-dimer > 1000 Sub-Study 3
             Health Care Worker Prevention

          -  Emergency Medicine or Infectious Disease Team physician or nurse at HUP or PPMC

          -  ≥20 hours per week of clinical work scheduled in the coming 2 months during the
             COVID-19 pandemic

          -  No fever, cough, or shortness of breath in the past 2 weeks

          -  Willing to report compliance with HCQ in the form of a diary

          -  Patients must be able to swallow and retain oral medication and must not have any
             clinically significant gastrointestinal abnormalities that may alter absorption such
             as malabsorption syndrome or major resection of the stomach or bowels.

        Exclusion Criteria <18 years of age

          -  Prisoners or other detained persons

          -  Allergy to hydroxychloroquine Pregnant or lactating or positive pregnancy test

          -  Receiving any treatment drug for 2019-ncov within 14 days prior to screening
             evaluation (off label, compassionate use or trial related).

          -  Co-enrollment onto another COVID-19 study is not allowed unless there is approval by
             the Medical Monitor in consultation with the PI and EM and ID sub-I leaders.

          -  Known history of retinal disease including but not limited to age related macular
             degeneration.

          -  Taking any of the following medications that prolong Qtc:

        Chlorpromazine.Haloperidol, Droperidol, Quetiapine, Olanzapine. Amisulpride. Thioridazine

          -  History of interstitial lung disease or chronic pneumonitis unrelated COVID-19.

          -  Due to risk of disease exacerbation patients with porphyria or psoriasis are
             ineligible unless the disease is well controlled and they are under the care of a
             specialist for the disorder who agrees to monitor the patient for exacerbations.

          -  Patients with serious intercurrent illness that requires active infusional therapy,
             intense monitoring, or frequent dose adjustments for medication including but not
             limited to infectious disease, cancer, autoimmune disease, cardiovascular disease.

          -  Patients who have undergone major abdominal, thoracic, spine or CNS surgery in the
             last 2 months, or plan to undergo surgery during study participation.

          -  Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (i.e.
             phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of
             the start of the study treatment

          -  History or evidence of increased cardiovascular risk including any of the following:

          -  Left ventricular ejection fraction (LVEF) < institutional lower limit of normal.
             Baseline echocardiogram is not required.

          -  A QT interval corrected for heart rate using the Frederica formula > 500 msec
             (Sub-study 2)

          -  Current clinically significant uncontrolled arrhythmias. Exception: Subjects with
             controlled atrial fibrillation

          -  History of acute coronary syndromes (including myocardial infarction and unstable
             angina), coronary angioplasty, or stenting within 6 months prior to enrollment

          -  Current ≥ Class II congestive heart failure as defined by New York Heart Association
      