Fig. 1. The four pillars of pandemic response to COVID-19. The four pillars of pandemic response to COVID-19 are:
1) contagion control or efforts to reduce spread of SARS-CoV-2,
2) early ambulatory or home treatment of COVID-19 syndrome to reduce hospitalization and death,
3) hospitalization as a safety net to prevent death in cases that require respiratory support or other invasive therapies,
4) natural and vaccination mediated immunity that converge to provide herd immunity and ultimate cessation of the viral pandemic.

As reported in the journal Reviews in Cardiovascular Medicine, Top US medics recommend ‘sequenced multidrug therapy’ including HCQ & Ivermectin, for early high-risk COVID-19 infections (source Palmer Foundation).  Bureaucratic public health officials obsessed with top-down, high-tech solutions have failed to provide citizens with the most important pillar: advice and the means to treat themselves and take charge of their own health care.  Excerpts in italics with my bolds.

The pandemic of SARS-CoV-2 (COVID-19) is advancing unabated across the world with each country and region developing distinct epidemiologic patterns in terms of frequency, hospitalization, and death. There are four pillars to an effective pandemic response:
1) contagion control,
2) early treatment,
3) hospitalization, and
4) vaccination to assist with herd immunity (Fig. 1).

Additionally, when feasible, prophylaxis could be viewed as an additional pillar since it works to reduce the spread as well as the incidence of acute illness.

Many countries have operationalized all four pillars including the second pillar of early home-based treatment with distributed medication kits of generic medications and supplements as shown in Table 1.

In the US, Canada, United Kingdom, Western European Union, Australia, and some South American Countries there have been three major areas of focus for pandemic response:
1) containment of the spread of infection (masking, social distancing, etc.,
2) late hospitalization and delayed treatments (remdesivir, convalescent plasma, antiviral antibodies), and
3) vaccine development (Bhimraj et al., 2020; COVID-19 Treatment Guidelines, 2020).

Thus the missing pillar of pandemic response is early home-based treatment (as seen in Fig. 1).

The current three-pronged approach has missed the predominant opportunity to reduce hospitalization and death given the practice of directing patients to self-isolation at home. Early sequential multidrug therapy (SMDT) is the only currently available method by which hospitalizations and possibly death could be reduced in the short term (McCullough et al., 2020a).

Innovative SMDT regimens forCOVID-19 utilize principles learned from hospitalized patients as well as data from treated ambulatory patients.

For the ambulatory patient with recognized signs and symptoms of COVID-19 on the first day (Fig. 2), often with nasal real-time reverse transcription or oral antigen testing not yet performed, the following three therapeutic principles apply (Centers for Disease Control and Prevention, 2020) :

1) combination anti-infective therapy to attenuate viral replication,
2) corticosteroids to modulate cytokine storm, and
4) antiplatelet agent/antithrombotic therapy to prevent and manage micro- or overt vascular thrombosis.

For patients with cardinal features of the syndrome (fever, viral malaise, nasal congestion, loss of taste and smell, dry cough, etc) with pending or suspected false negative testing, therapy is the same as those with confirmed COVID-19.

Fig. 3. Sequential multidrug treatment algorithm for ambulatory acute COVID-19 like and confirmed COVID-19 illness in patients in self-quarantine. Yr = year, BMI = body mass index, Dz = disease, DM = diabetes mellitus, CVD = cardiovascular disease, chronic kidney disease, HCQ = hydroxychloroquine, IVM = ivermectin, Mgt = management, Ox = oximetry, reproduced with permission from reference.

Summary

The SARS-CoV-2 outbreak is a once in a hundred-year pandemic that has not been addressed by rapid establishment of infrastructure amenable to support the conduct of large, randomized trials in outpatients in the community setting.

The early flu-like stage of viral replication provides a therapeutic window of tremendous opportunity to potentially reduce the risk of more severe sequelae in high risk patients. Precious time is squandered with a “wait and see” approach in which there is no anti-viral treatment as the condition worsens, possibly resulting in unnecessary hospitalisation, morbidity, and death.

Once infected, the only means of preventing a hospitalization in a high-risk patient is to apply treatment before arrival of symptoms that prompt paramedic calls or emergency room visits. Given the current failure of government support for randomized clinical trials evaluating widely available, generic, inexpensive therapeutics, and the lack of instructive out-patient treatment guidelines (U.S., Canada, U.K., Western EU, Australia, some South American Countries), clinicians must act according to clinical judgement and in shared decision making with fully informed patients.

Early SMDT developed empirically based upon pathophysiology and evidence from randomized data and the treated natural history of COVID-19 has demonstrated safety and efficacy.

In newly diagnosed, high-risk, symptomatic patients with COVID-19, SMDT has a reasonable chance of therapeutic gain with an acceptable benefit-to-risk profile.

Until the pandemic closes with population-level herd immunity potentially augmented with vaccination, early ambulatory SMDT should be a standard practice in high risk and severely symptomatic acute COVID-19 patients beginning at the onset of illness.

Authors:

Peter A. McCullough, Paul E. Alexander, Robin Armstrong, Cristian Arvinte, Alan F. Bain, Richard P. Bartlett, Robert L. Berkowitz, Andrew C. Berry, Thomas J. Borody, Joseph H. Brewer, Adam M. Brufsky, Teryn Clarke, Roland Derwand, Alieta Eck, John Eck, Richard A. Eisner, George C. Fareed, Angelina Farella, Silvia N. S. Fonseca, Charles E. Geyer Jr., Russell S. Gonnering, Karladine E. Graves, Kenneth B. V. Gross, Sabine Hazan, Kristin S. Held, H. Thomas Hight, Stella Immanuel, Michael M. Jacobs, Joseph A. Ladapo, Lionel H. Lee, John Littell, Ivette Lozano, Harpal S. Mangat, Ben Marble, John E. McKinnon, Lee D. Merritt, Jane M. Orient, Ramin Oskoui, Donald C. Pompan, Brian C. Procter, Chad Prodromos, Juliana Cepelowicz Rajter, Jean-Jacques Rajter, C. Venkata S. Ram, Salete S. Rios , Harvey A. Risch, Michael J. A. Robb, Molly Rutherford, Martin Scholz, Marilyn M. Singleton, James A. Tumlin, Brian M. Tyson, Richard G. Urso, Kelly Victory, Elizabeth Lee Vliet, Craig M. Wax, Alexandre G. Wolkoff, Vicki Wooll, Vladimir Zelenko. Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19). Reviews in Cardiovascular Medicine, 2020, 21(4): 517-530.