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Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta
Ivermectin Meta
Thermotherapy Meta
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COVID-19 treatment: high-profit systemic drugs

• High-profit treatments are effective, but have access and cost barriers

We do not provide medical advice. No treatment is 100% effective, and all may have side effects. Protocols combine multiple treatments. Consult a qualified physician for personalized risk/benefit analysis.
Over 9,000 compounds predicted to reduce COVID-19 risk. SARS-CoV-2 is easily disabled. SARS-CoV-2 infection and replication involves a complex interplay of over 100 host and viral proteins and other factors1-8, providing many therapeutic targets. Scientists have identified 9,042+ compounds9 potentially beneficial for COVID-19. Hundreds of compounds inhibit SARS-CoV-2 in vitro, including many with known pharmacokinetics and proven safety.
Pfizer has received over US$10 billion in penalties for 90+ violations including false claims and drug safety violations10.
Paxlovid. Paxlovid was effective11-92, but has significant side effects, increased risk of replication-competent viral rebound41, and extensive contraindications93,94. Resistant variants are likely95-100 and efficacy with current variants may be lower. The degree of efficacy during the pandemic is unclear—Pfizer RCTs report very good results, while non-Pfizer RCTs33,74 show relatively poor results, and Pfizer has denied access for other independent trials101. About one third of people may be at risk of a major or contraindicated drug interaction, which may increase significantly for patients over 60 or with several comorbidities that also increase COVID-19 risk94,102. Hoertel et al. found that over 50% of COVID-19 patients that died had a contraindication for paxlovid. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID104. Observational studies are often highly confounded—in population studies the group of patients that seek out and receive paxlovid is very different to the control group in ways not covered by typical adjustments. Patients identified as taking paxlovid are also patients that may be more conscientious, have improved access to the medical system, are more likely to receive care in case of progression, are more likely to take additional measures or known beneficial non-prescription treatments, and are more likely to be advised of the same due to contact with the medical system. Studies are also often confounded via immortal time bias and failure to exclude contraindicated patients in the control group.
3CLpro inhibitors. Paxlovid inhibits SARS-CoV-2 3CLpro, a key enzyme in the viral replication process. In addition to existing compounds that function as 3CLpro inhibitors, e.g., quercetin and curcumin, many novel compounds have been developed. Paxlovid is unlikely to be the most effective, the safest90,103,105,106, or the most resistant to variants95-100, however it is the most profitable. Other novel 3CLpro inhibitors showing reduced risk for COVID-19 include atilotrelvir, ibuzatrelvir, and leritrelvir107-113.
Merck has received over US$10 billion in penalties for 80+ violations including false claims and drug safety violations114.
Molnupiravir. Molnupiravir is likely effective54,61,67,68,85,86,115-160, with precise efficacy unclear due to similar issues regarding conflicts of interest in RCTs and confounding in population studies. However, potential mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity147,161-173, the increased risk of creating new dangerous variants174-178, an association with increased viral persistence147, and the existence of many other options collectively rule out use in humans. Molnupiravir has been used for creating variants to test the resistance of treatments to escape mutations179.
Protocols typically combine multiple treatments. No single treatment is guaranteed to be effective and safe for a specific individual. Leading evidence-based protocols combine multiple treatments.
c19early.org
Combined treatments increase efficacy
Monotherapy33% [30‑36%]
Polytherapy68% [57‑77%]
Meta analysis of early treatment studies.
Complementary and synergistic actions. There are many complementary mechanisms of action across treatments, and studies show complementary and synergistic effects with polytherapy180-196. For example, Jitobaom et al.181 showed >10x reduction in IC50 with ivermectin and niclosamide, an RCT by Said et al.188 showed the combination of nigella sativa and vitamin D was more effective than either alone, and an RCT by Wannigama et al.197 showed improved results with fluvoxamine combined with bromhexine, cyproheptadine, or niclosamide, compared to fluvoxamine alone. Treatment efficacy may vary significantly across SARS-CoV-2 variants. For example new variants may gain resistance to targeted treatments95-100,198, and the role of TMPRSS2 for cell entry differs across variants199. The efficacy of specific treatments varies depending on cell type200 due to differences in viral receptor expression, drug distribution and metabolism, cell-specific mechanisms, and the relevance of drug targets to specific cells. Efficacy may also vary based on genetic variants201-204. Variable efficacy across SARS-CoV-2 variants, cell types, different tissues, and host genetics, along with the complementary and synergistic actions of different treatments, all point to greater efficacy with polytherapy. In many studies, the standard of care given to all patients includes other treatments—efficacy seen in these trials may rely in part on synergistic effects. Meta analysis of all early treatment trials shows 68% [57‑77%] lower risk for studies using combined treatments, compared to 33% [30‑36%] for single treatments.
SARS-CoV-2 evolution and the risk of escape mutants suggests treatments with broader mechanisms of action and polytherapy. SARS-CoV-2 can rapidly acquire mutations altering infectivity, disease severity, and drug resistance even without selective pressure205. Antigenic drift can undermine more variant-specific treatments like monoclonal antibodies and more specific antivirals. Treatment with targeted antivirals may select for escape mutations206. Less variant specific treatments and polytherapy targeting multiple viral and host proteins may be more effective.
Systemic antivirals may be less applicable to low-risk infections. As SARS-CoV-2 has evolved, the frequency of serious infections has reduced. Systemic antivirals may have a more limited effect if infection does not spread beyond the upper respiratory tract.
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
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