Physician Secrets Revealed: Outpatient Treatment For Covid-19

Physician Secrets Revealed: Outpatient Treatment For Covid-19

SARS-CoV-2 infection (COVID-19) illness involves viral-mediated organ damage, cytokine storm, and thrombosis. Once ill, the only method of reducing the risk of hospitalization and death is medical treatment in the ambulatory phase using the same principles for hospitalized patients. Early therapy that has a reasonable chance of success and an acceptable safety profile includes: 1) combination antiviral therapy, 2) corticosteroids, 3) antiplatelet agents/antithrombotics, 4) supportive care including supplemental oxygen, monitoring, and telemedicine. The current rates of hospitalization and death are unacceptably high under the present paradigm of contagion control and watchful waiting for a vaccine. A pivot towards immediate, early ambulatory treatment must occur at this time.

The SARS-CO-V2 (COVID-19) global crisis has driven considerable efforts on the pandemic response which can be viewed as having four pillars:

1) contagion control, 

2) early ambulatory treatment to reduce hospitalization and death,

3) hospitalization as a safety net to save lives at the critical stage, and

4) herd immunity through vaccination and prior COVID-19 illness.

Unfortunately efforts at contagion control have failed, hospitalization is not an adequate safety net, and vaccination is not currently available.1 Across the globe we must turn our attention to the least emphasized pillar of early ambulatory treatment.2 There are a wide range of responses on early treatment to multi-drug home treatment kits deployed in countries such as India, Brazil, Guatemala, and Salvador to near-complete prohibition of ambulatory treatment in the U.S., Canada, United Kingdom, Western European Union, and Australia.3 Penalties for an Australian physician who attempts to prescribe a therapy such as hydroxychloroquine in an acutely ill COVID-19 patient can include imprisonment.4 Never has modern medicine witnessed such disparate courses of action for doctors and patients.

After approximately ~50,000 publications on COVID-19 cited in the National Library of Medicine, a U.S-Italian Collaboration published the first guidance on the scientific rationale for early ambulatory treatment of COVID-19 as the only hope to reduce the chances of hospitalization or death once COVID-19 is contracted.5  These guidelines have been updated and adapted as shown in this figure and largely apply to adults over age 50 and those with medical comorbidities.  


The principles include using off-target antiviral treatment (hydroxychloroquine, ivermectin, favipiravir, combined with an antibiotic [azithromycin, doxycycline] to provide synergism and coverage for bacterial superinfection as soon as possible even before confirmatory testing is completed.6 7 By day five or if any pulmonary symptoms develop, treatment of cytokine storm with corticosteroids is the next step. Finally, given the disastrous risk of micro- and macro-thromboembolism with activation of thromboxane A2 and the development of antiphospholipid antibodies, full dose aspirin and intensification of treatment to include low-molecular-weight heparin or novel oral anticoagulants is advised. 9 10

The shortest course of treatment with full resolution of symptoms is five days, average is 10 days, and for older individuals with multiple comorbidities or senior facility residents, a full 30 days of treatment is advised.  

The COVID-19 pandemic has called for superior discernment of an evolving yet imperfect universe of scientific information forged with clinical judgment and the art of medicine as the only immediate path to stem the tide of hospitalizations and death. The second pillar of pandemic response deserves the highest attention by public health officials and the U.S-Italian treatment algorithm should be front and center in the COVID-19 global crisis.3 


1-  Vahidy FS, Drews AL, Masud FN, et al. Characteristics and Outcomes of COVID-19 Patients During Initial Peak and Resurgence in the Houston Metropolitan Area [published online ahead of print, 2020 Aug 13]. JAMA. 2020;324(10):998-1000. doi:10.1001/jama.2020.15301

2- McCullough PA, Arunthamakun J. Disconnect between community testing and hospitalization for SARS-CoV-2 (COVID-19) infection. Proc (Bayl Univ Med Cent). 2020 May 14;33(3):481. doi: 10.1080/08998280.2020.1762439. PMID: 32675999; PMCID: PMC7340440.

3- (accessed November 8, 2020)

4- (accessed November 8, 2020)

5- McCullough PA, Kelly RJ, Ruocco G, Lerma E, Tumlin J, Wheelan KR, Katz N, Lepor NE, Vijay K, Carter H, Singh B, McCullough SP, Bhambi BK, Palazzuoli A, De Ferrari GM, Milligan GP, Safder T, Tecson KM, Wang DD, McKinnon JE, O’Neill WW, Zervos M, Risch HA. Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. Am J Med. 2020 Aug 7:S0002-9343(20)30673-2. doi: 10.1016/j.amjmed.2020.07.003. Epub ahead of print. PMID: 32771461; PMCID: PMC7410805.

6- Ladapo JA, McKinnon JE, McCullough PA, Risch H.  Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis.  medRxiv 2020.09.30.20204693; doi:

7- McCullough PA. Favipiravir and the Need for Early Ambulatory Treatment of SARS-CoV2 Infection (COVID-19). Antimicrob Agents Chemother. 2020 Sep 23:AAC.02017-20. doi: 10.1128/AAC.02017-20. Epub ahead of print. PMID: 32967849.

8- Cano EJ, Fuentes XF, Campioli CC, O’Horo JC, Saleh OA, Odeyemi Y, Yadav H, Temesgen Z. “Impact of Corticosteroids in COVID-19 Outcomes: Systematic Review and Meta-Analysis”. Chest. 2020 Oct 28:S0012-3692(20)35107-2. doi: 10.1016/j.chest.2020.10.054. Epub ahead of print. PMID: 33129791.

9- Mahajan P, Dass B, Radhakrishnan N, McCullough PA. COVID-19-Associated Systemic Thromboembolism: A Case Report and Review of the Literature. Cardiorenal Med. 2020 Oct 22:1-8. doi: 10.1159/000511800. Epub ahead of print. PMID: 33091905.

10- Singhania N, Bansal S, Nimmatoori DP, Ejaz AA, McCullough PA, Singhania G. Current Overview on Hypercoagulability in COVID-19. Am J Cardiovasc Drugs. 2020 Oct;20(5):393-403. doi: 10.1007/s40256-020-00431-z. PMID: 32748336; PMCID: PMC7398761.

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