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The evidence had accumulated very early on in the pandemic that the use of sequenced multi-drug therapeutics (SMDT) under physician guidance was beneficial and that some medications were safe and effective. We refer to repurposed therapeutics that have been regulatory approved and have been used in some instances for decades for other illnesses. In this accumulation, we had giants in academic research, clinicians, and specialists such as Drs. McCullough, Amerling, Gold, Littell, Risch, Oskoui, Zelenko, Urso, Ladapo, Kory, Todaro, Bhattacharya, Malone, Marik, Vanden Bossche, Armstrong, Fareed, Alexander, Tenenbaum etc. on the front line showcasing the tremendous benefits of early treatment in reducing risk of hospitalization and death. They were pilloried and silenced. 

We have extensively written and published treatment algorithms and protocols as well as evidence of the benefit of early outpatient (ambulatory) treatment of SARS-CoV-2 virus and the consequent disease COVID-19 (1, 2, 3, 4, 5, 6). With highly targeted and SMDT regimens that include early application of antiviral drugs, combined with corticosteroids and anti-platelet/anti-thrombotic/anti-clotting therapeutics, the risk of hospitalization is significantly reduced by as much as by 85 to 90%, and risk of death is eliminated for high-risk patients and younger individuals presenting with severe symptoms.

COVID-19 presents as either a mild-flu-like condition (asymptomatic or mild symptoms) or more serious illness in those at high risk. A small fraction of persons infected with COVID virus progress to more serious illness (typically elderly with underlying medical conditions, obese or younger with underlying medical conditions/risks factors). The complex and multidimensional pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the illness.

As a brief background, the illness involves three phases 1) an initial viral replication phase whereby the virus hijacks the metabolic machinery of the cells which then begins to synthesize new viral particles ii) a more advanced inflammatory hyper-dysregulated immune-modulatory florid pneumonia phase whereby there is a cytokine storm and problematic gas exchange known as acute respiratory distress syndrome; ARDS. ARDS is generally the cause of most deaths attributed to COVID-19; and iii) a thrombotic blood clotting phase whereby microthrombi develop within the lungs and in the vasculature, leading to disastrous complications including profound hypoxemia, stroke, and heart attacks.

The ideal situation is to arrest the virus in the initial phase when symptoms have just emerged, while the patient is still within the home setting or extended care setting. The goal is to prevent hospitalization and death.

In countries where there is and was a reluctance to treat infected and symptomatic high-risk persons early, this therapeutic nihilism resulted in escalating symptoms, delayed in-hospital care and death. Fortunately, prompt and early initiation of SMDT is a widely and currently available solution to stem the tide of hospitalizations and death.

Viral illnesses such as COVID-19, with complex pathophysiology, do not respond to one drug treatment but require a multi-drug approach. We have to hit the virus with multiple therapeutics. This multipronged therapeutic approach includes 1) adjuvant nutritional supplements; 2) combination intracellular anti-infective therapy (antivirals and antibiotics); 3) inhaled/oral corticosteroids and colchicine; 4) antiplatelet agents/anticoagulants; 5) supportive care including supplemental oxygen, monitoring and telemedicine.

Randomized trials of individual, novel oral therapies have not delivered effective tools. No single therapeutic option thus far has been adequate, but combinations have been employed very successfully in clinical practice. Treating physicians who were courageous and brave felt it was urgent to apply the SMDT approach universally to benefit large numbers of acute COVID-19 patients, reducing their intensity and duration of symptoms and saving them from hospitalization and death. The key is use of early treatment as soon as symptoms develops when the virus is early in the replication phase.

This brief compilation (Table 1 and Figures 1 & 2) describes a cursory summary with the direct url links of therapeutics that have been shown some degree of effectiveness if infected with COVID-19 virus in any of its variant forms including Delta and Omicron.

While the COVID-19 emergency is winding down, with Omicron offering an exit off-ramp, variants, including the Delta and Omicron variant, still exist and will continue to. We therefore felt the public (and particularly those at high-risk) should be aware of known treatment options. While most people and especially young persons and children are indeed at very low risk of illness and especially from the very mild near ‘common-cold’ Omicron variant, this early treatment guidance provides an important resource that can be life saving when needed.

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