This is a randomized, open-label trial to assess the safety and efficacy of hydroxychloroquine, and zinc in combination with either azithromycin or doxycycline in a higher risk COVID-19 positive outpatient population.

COVID-19 is an aggressive and contagious virus, found to have high mortality especially in persons with comorbidities (Age>60, hypertension [HTN], diabetes mellitus [DM], Cancer, and otherwise immunocompromised). Zinc is a supplement with possible antiviral properties, having been shown to have effect in the common cold, many of which are due to coronavirus. In addition, elderly patients and patients with co-morbidities have high incidence of zinc deficiency. We are repleting zinc in all patients and studying its direct effect in combination with hydroxychloroquine, and an antibiotic, either azithromycin or doxycycline to see if there is enhanced treatment efficacy in early COVID-19 infection and assess the safety of these two regimen.

Inclusion Criteria:

• Able to read and understand informed consent.

• High initial clinical suspicion by physician based on signs and symptoms (fever, cough, myalgias, fatigue, shortness of breath) followed by RT-PCR for confirmation of COVID-19 diagnosis

• Any gender

• Age 60 years and older

• Age 30-59 years with one or more of the following:

  • abnormal lung exam
  • abnormal oxygen staturation <95%
  • abnormal chest x-ray or chest CT
  • persistent fever >100.4 degrees Fahrenheit upon arrival to Emergency department (ED)
  • one of the following co-morbidities: hypertension, diabetes mellitus, history of coronary artery disease, chronic kidney disease (CKD), asthma, chronic obstructive pulmonary disease, current or former smoker, or morbid obesity (Body Mass Index ≥35)

Exclusion Criteria:

• Pregnant or breastfeeding female
• Severe COVID-19 requiring admission for inpatient treatment
• Need for any oxygen supplementation
• Need for mechanical ventilatory support
• History of oxygen supplementation dependency
• History of cancer with ongoing chemotherapy or radiation therapy
• Concurrent antimicrobial therapy
• Known hypersensitivity to hydroxychloroquine or other 4-aminoquinoline compounds
• Already taking hydroxychloroquine or chloroquine within 1 month
• Known G6-PD deficiency
• History of retinopathy
• History of current cardiac diseases (heart failure, ventricular arrhythmias, Left bundle branch block and/or Right bundle branch block, QTc prolongation >480ms), or family history of sudden cardiac death
• Ongoing use of drugs that prolong the QTc interval (antipsychotics, antidepressants, class I and III antiarrhythmics, triptans)
• Severe renal disease: glomerular filtration rate (GFR) <30ml/min
• Severe hepatic impairment (elevated total bilirubin >2 mg/dL, decreased albumin <2.8 g/dL, signs of jaundice and ascites.)
• Active alcohol abuse (>5 drinks per day or >20 drinks per week.)
• Seizure disorder, currently on medications
• Known hypersensitivity to any tetracyclines.