key: cord-0954297-fo7xre9x
authors: McCullough, Peter A.
title: The Reply
date: 2021-05-04
journal: Am J Med
DOI: 10.1016/j.amjmed.2021.01.011
sha: 3f05171c9a4067c9aace2104a45e5cfd7ddaf526
doc_id: 954297
cord_uid: fo7xre9x

nan

We respectfully join Dr. Weissmann and colleagues in a call for large high-quality randomized trials in coronavirus disease . This potentially fatal viral illness requires multiple drugs from different therapeutic categories to successfully manage, preferably on an ambulatory basis and not during a hospitalization. Unfortunately, in our view 1 there are no conclusive randomized trials of either single or more appropriately multiple drugs with double dummies in ambulatory patients. To our knowledge, no such trials are forthcoming. Thus, we must act on clinical judgment supported by our understanding of pathophysiology, and the totality of evidence concerning therapy. 2 Oral steroids are now better supported by multiple trials and observational studies, including the use of prednisone. 3, 4 The rationale for either azithromycin or doxycycline to complete a pair of oral, intracellular antiinfective agents remains unchanged. 2 Finally, since the time of our original publication, early ambulatory treatment has become an emerging standard in over 30 countries, including several states in Brazil where home treatment kits are utilized relying upon the principles we have published. 2 We invite Dr. Weissman and colleagues to join us in breaking therapeutic nihilism toward ambulatory patients with COVID-19-this has led to catastrophic levels of fear, suffering, hospitalization, and death. Sources of real-word data suggest early ambulatory sequenced multidrug therapy is associated with~85% reductions in morbidity and mortality due to COVID-19 with no signals of harm. 2, 5, 6, 7 

Pathophysiological basis and rationale for early outpatient treatment of SARS-CoV-2 (COVID-19) infection

Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis

Risk of hospitalization for COVID-19 outpatients treated with various drug regimens in Brazil: comparative analysis

Early ambulatory multidrug therapy reduces hospitalization and death in high-risk patients with SARS-CoV-2 (COVID-19

Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection

COVID-19 outpatients: early riskstratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study