key: cord-1034896-2i51eyfq
authors: Korman, Tony M
title: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients
date: 2020-07-20
journal: Am J Epidemiol
DOI: 10.1093/aje/kwaa154
sha: fcd50a2d0524fdf004f4cc2d7bd32dd9d9dd9909
doc_id: 1034896
cord_uid: 2i51eyfq

nan

Risch makes an impassioned plea that we are "unable to wait for results of randomized controlled trials" for COVID-19 and should "immediately roll out" early outpatient treatment with hydroxychloroquine (HCQ) and azithromycin (AZ). 1 Early treatment that prevents disease progression and hospitalization is desperately needed, and timing of initiation of antiviral therapy may have important effects on the outcomes of therapy for COVID-19. 2 Unfortunately, "based on laboratory and other preliminary evidence to-date", no treatment is available "effective in preventing hospitalization for the overwhelming majority", and there are potential hazards associated with HCQ+AZ. Gautret et al. reported an open-label non-randomized study which showed a significant reduction of patients with detectable virus but included only six patients treated with HCQ+AZ and injudiciously recommended "that COVID-19 patients be treated with HCQ+AZ to cure their infection and to limit the transmission of the virus". 3 The International Society of Antimicrobial Chemotherapy and the journal publisher have acknowledged that "concerns have been raised regarding the content, the ethical approval of the trial and the process that this paper underwent to be published" and additional independent peer review is ongoing. 4 Risch contends that criticism regarding the small study size "only applies to studies not finding statistical significance" and that "once a result has exceeded plausible chance finding, greater statistical significance does not contribute to evidence for causation".

However, small trials with very large treatment effects, in particular those with laboratorydefined efficacy, should be considered with caution, and subsequent trials typically show decreased effects and many lose their nominal significance. 5 In a follow up study from

Marseilles of 1061 patients (which excluded 256 patients with "contraindications to HCQ and/or AZ treatment, refusal or other reasons"), 4.4% had persistent viral shedding at day 10, 4.3% had "poor clinical outcome" (death or transfer to ICU or hospitalization for 10 days or more) with a case fatality rate of at least 0.75%. 6 Risch cites other non-peer reviewed "evidence". A non-randomized trial from São Paulo,

Brazil showed a reduced hospitalization rate for 636 outpatients treated with HCQ+AZ (1.9%) compared to a "control" group of 224 patients who "refused treatment" (5.4%). 7. A New York Family Practitioner proclaimed that of "approximately" 405 patients treated with

HCQ+AZ+zinc sulfate, six were hospitalized for pneumonia and only two died. 8 Both of these reports included patients diagnosed "on clinical grounds", without laboratory confirmation. 

Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis

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