Early Outpatient Treatment of Symptomatic, High-Risk COVID-19 Patients That Should Be Ramped Up Immediately as Key to the Pandemic Crisis

Am J Epidemiol. 2020 Nov 2;189(11):1218-1226. doi: 10.1093/aje/kwaa093.


More than 1.6 million Americans have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 10 times that number carry antibodies to it. High-risk patients with progressing symptomatic disease currently have only hospitalization treatment, with its high mortality, available to them. An outpatient treatment that prevents hospitalization is desperately needed. Two candidate medications have been widely discussed: remdesivir and hydroxychloroquine (HCQ) + azithromycin (AZ). Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials in outpatients have been registered. HCQ + AZ has been widely misrepresented in both clinical reports and public media, and results of outpatient trials are not expected until September. Early outpatient illness is very different from later florid disease requiring hospitalization, and the treatments differ. Evidence about use of HCQ alone, or of HCQ + AZ in inpatients, is irrelevant with regard to the efficacy of HCQ + AZ in early high-risk outpatient disease. Five studies, including 2 controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. HCQ + AZ has been used as the standard of care in more than 300,000 older adults with multiple comorbid conditions; the estimated proportion of such patients diagnosed with cardiac arrhythmia attributable to the medications is 47 per 100,000 users, among whom estimated mortality is less than 20% (9/100,000 users), as compared with the 10,000 Americans now dying each week. These medications need to be made widely available and promoted immediately for physicians to prescribe.

Keywords: COVID-19; SARS-CoV-2; azithromycin; coronavirus; doxycycline; hydroxychloroquine; remdesivir; zinc.

MeSH terms

  • Aged
  • Antiviral Agents / therapeutic use*
  • Azithromycin / therapeutic use*
  • Betacoronavirus
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Female
  • Humans
  • Hydroxychloroquine / adverse effects
  • Hydroxychloroquine / therapeutic use*
  • Male
  • Outpatients
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • SARS-CoV-2
  • Treatment Outcome


  • Antiviral Agents
  • Hydroxychloroquine
  • Azithromycin