CDC Informed About a Combination Therapy that Should Cure 80% of H5N1 Influenza Cases

Dear Center for Disease Control, NCIRD, Influenza Section,

            A month ago, only one version of avian influenza was spreading among cattle in the U.S., H5N1 B3.13. Now two additional versions of avian flu are spreading, H5N1 D1.1 and H5N9. Just as worrying, scientists now believe the virus can be spread via the airborne dust of desiccated waterfowl feces, and perhaps from pet cats to people. But you already know this. What no one can predict is how soon the virus may reassort with seasonal flu or mutate to become easily transmittable between people, which variant will go pandemic, or what the eventual case mortality rate will be.

            When SARS-CoV-2 (SARS-2) was first announced in January 2020, because of my 30 years studying viral pandemic disease I instantly knew the broad-spectrum antiviral medicines aspirin and selenium would be effective against Covid-19. By the end of February, I had written two essays explaining why aspirin and selenium should be used against coronavirus and in March sent several emails from Johannesburg to Anthony Fauci’s deputy at the NIH urging them to use what they too should have known would be effective. Those essays and emails are included in my book Understanding Covid-19, How 500,000 American Lives Could Have Been Saved. However, wearing therapeutic blinders, the NIH and CDC ignored the established science. Despite the eventual success with vaccines, 1.2 million Americans died of Covid. Based on an understanding of the published science as of early 2020, if selenium and aspirin had been used as early therapy from the start, 2/3 of Covid deaths in America probably could have been avoided. Although the atmosphere of the Covid Crisis of 2020-2021 was saturated with therapeutic confusion, scientific distortion, misinformation, and outright lies, the most detrimental falsehood was that there were no effective drugs to treat early onset Covid. There were. True, there were no cures. However, both the CDC and NIH should have been aware that scientists had shown that both aspirin and selenium clearly have a significant effect against viral respiratory disease. That fact was salted throughout relevant medical journals if anyone had “done the research” that is reported here. Indeed, existing science was completely ignored and the counterproductive woe-is-me-ism of “there are no drugs to treat early Covid infection” was repeatedly broadcast to the world by public health officials without a second thought to the existing science. Will the CDC repeat that tragically fatal mistake again so soon with H5N1 highly pathogenic avian influenza (HPAI)? Or have we learned any lessons from Covid-19? Obviously, it is difficult to learn a lesson if one fails to recognize the original mistake.

            Citing the gross insufficiency of the current medical armamentarium of specific anti-flu drugs due to their universal long-term failure to overcome the challenge of viral resistance, every concerned scientist remarks on the urgent need to develop better drugs to treat H5N1, H5N9 or any highly pathogenic variant that turns up in the U.S. after another goose uses the North Atlantic flyway to wing the next clade of HPAI from Eurasia to the Americas. The unspoken mantra that “new diseases require new drugs” has blinded critically important public health institutions like the CDC to the fact that additional proven effective drugs already exist to fight influenza. Being intellectually wedded to the specific-drug antiviral paradigm completely obscures the more practical therapeutic potential of broad-spectrum antivirals. It is a conceptual catastrophe to focus therapeutically solely on inhibiting H5N1 replication that declines after a few days, while largely ignoring the importance of treating the disease it triggers from the start. We need to treat the immune ramifications of influenza from their inception, not just try to inhibit the virus.

            When Virginia Senator Tim Kaine’s office contacted me last August to write something explaining the impending danger of H5N1, they said they would send my analysis to the NIH and CDC to ask what they thought. I took the assignment seriously. I am attaching the 48-page essay “Therapeutic Strategy to Survive H5N1 Avian Influenza, Reduce Extreme HPAI Mortality Rates and Improve Pandemic Preparedness – Part 1: Early Therapy” that resulted from four months research reviewing over 450 medical journals articles. Section 8 reviews the scientific basis for using three effective broad-spectrum anti-influenza medications – selenium, aspirin, and naproxen – SAN therapy. These three medicines can be used prophylactically as well as therapeutically against not only influenza but other viral respiratory diseases as well. No single medicine is 100% effective against HPAI. However, these three drugs working together through multiple mechanisms of action should be able to reduce the eventual case mortality rate of H5N1 by in the range of 80-90% if applied properly as suggested in the essay. Besides working through over a dozen different immunological and cellular mechanisms to inhibit viral replication and the resulting disease pathogenesis and sequelae, a critical fact is that unlike with specific antiviral drugs, viruses do not develop resistance to these three medications. In addition, selenium, aspirin and naproxen can be combined safely with the current anti-viral drugs, Tamiflu and Xofluza. Selenium aspirin and naproxen are all widely available and affordable. They easy and safe enough to use at home, beginning the moment a person feels the telltale symptoms of flu – high fever and body-ache. As most physicians acknowledge, early therapy is the best therapy. That is particularly important with HPAI because early viral activation of platelets in the lungs triggers the preliminary inception of the cytokine storm that leads to sepsis, multiple organ failure (MOF) and death. The fact that influenza viral replication peaks approximately 48 hours after the initial infection also calls for immediate therapy, with no delay if possible. That is possible with SAN influenza first aid therapy.  

            My extensive but not exhaustive review of the relevant medical journal literature turned up at least 25 journal articles that explain how and why selenium helps against influenza and other respiratory viruses, 20 articles explaining how aspirin helps, and 7 about how naproxen helps against both influenza and coronaviruses. The research reported here was mostly conducted between 2000 and 2020. Thus, if anyone had cared to review it at the beginning of the last pandemic in 2020, the benefit of these scientific findings could have been used to save lives by providing early therapy against Covid-19 in 2020 and 2021, just as I had suggested to the NIH in March 2020. However blindly following the tunnel vision leadership at the National Institute of Allergy and Infectious Disease (NIAID) that focused solely on new drug development, the CDC failed to utilize the scientific advances of the last twenty years of viral respiratory research to benefit the American public. As a result, the whole world suffered. Focusing on only “specific” antiviral drugs to the exclusion of broad-spectrum antiviral drugs is like a person going through life blinded in one eye, or with one hand tied behind their back. I urge the CDC to add the major advantages provided by known, broad-spectrum antiviral medicines to those of specifically targeted anti-flu drugs. Overcoming viral resistance is only one of many advantages physicians and patients gain by adding broad-spectrum antiviral drugs to the current specific-drugs that, unfortunately, influenza viruses quickly develop resistance to.

            Broad-spectrum antiviral drugs work by inhibiting both viral replication and retarding various aspects of disease pathogenesis and progression. Most of the effects reported in medical journals for each of the three medications are listed below. The direct antiviral effects for each medicine are listed separately from the additional therapeutic effects the medication provides against viral respiratory disease. For brevity’s sake, only one reference is provided in each instance. The full references are found at the end of the essay.   

Selenium (Se) - direct antiviral effects: 1. nuclear factor-kappaB inhibitor (NF-kBI) (Hatfield); 2.                         protease inhibitor (Jin); 3. provides viral prophylaxis (Jahromi); 4. interferes with viral                             attachment by inhibiting the disulfide exchange reaction (Tomo)                                                                                       

          Se effects that retard respiratory disease pathogenesis: 1. antioxidant, immunomodulator and platelet antagonist (Hatfield); 2. reduces sepsis (Alhazzani); 3. increases CD4 (Odunukwe); 4. anti-inflammatory (Beck); 5. reduces pneumonitis (Beck); 6. reduces lung pathology and lung tissue damage (Beck); 7. improves lung CD8+ count (Beck); 8. increases GSHPx (Beck) and GPx-1 (Yatmaz); 9. reduces flu virulence and progression (Gill); 10. reduces ventilator-associated pneumonia (Manzanares); 11. reduces sequential organ failure assessment (SOFA) score (Manzanares); 12. reduces Ebola mortality rate (personal report) 13. reduces blood clotting/distributed intravascular coagulation (DIC) (Geinbert); 14. retards viral genomic evolution and resistance (Guillin); 15. reduces viral pathogenicity (Guillin); 16. reduces viral-related mortality (Alhazzani); 17. reduces septic shock (Forceville); 18. reduces severe septic mortality (Angstwurm); 19. strengthens immunity against viral infection (Taylor); 20. restores antioxidant capacity of the lungs and improves respiratory mechanics (Zhang); 21. suppresses the cytokine storm (Zhang); 22. reduces SARS-2 replication (Jin); 23. “protects against ferroptotic cell death” (Y. Wang) 24. increases GPx-4 and TXNRD3 antioxidants (Y. Wang); 25. reduces lymphocyte oxidative cell death (Y. Wang) 26. out of 10,000 chemicals tested a selenium-based drug Ebselen was rated number one in inhibiting SARS-CoV-2 replication (Jin)      

Aspirin (ASA) – direct antiviral effects: 1. NF-kappaBI (Tanaka); 2. inhibits AP-1 replication factor                     (Du); 3. retains the “viral RNP complex in the nucleus” (Mazur)

   ASA effects that retard respiratory disease pathogenesis: 1. immunomodulator with anticoagulant effects (Di Bella); 2. COX-1 inhibitor (Sugiyama); 3. inhibits H5N1 via NF-kB inhibition (Mazur); 4. provides analgesic and anti-inflammatory relief (Mazur); 5. reduces incidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) (Erlich); 6. reduces systematic inflammatory response syndrome (SIRS) related mortality (Eisen); 7. reduces ICU and sepsis patient mortality (Eisen); 8 increases resolvin D1 (RvD1) thus reducing ALI (Eichmeier); 9. decreases ARDS morbidity and mortality (Eichmeier); 10. reduces the cytokine storm (Eichmeier); 11. reduces sepsis (Chen); 12. decreases neutrophil activation (Chen); 13. reduces tumor necrosis factor-alpha (TNF-a) (Chen); 14. decreased risk of lung dysfunction and multiple organ failure (Chen); 15.     reduces neutrophil cell d    eath (Boyle); 16. reduces sepsis-related mortality (Boyle); 17. inhibits platelet activation (Le); 18. platelet inhibition improves influenza survival (Sugiyama); 19. adding ASA to M2 ion channel inhibition increased experimental mice survival rate from only 10% to 80%. (Sugiyama); 20. increases arterial oxygenation (Sugiyama); 21. reduces C-reactive protein (CRP), TNF-a, interleukin-6 (IL-6), and thromboxane B2 (TXB2) (Gao); 22. inhibits influenza A  (IAV) replication (Glatthaar-Saalmuller); 23. reduces post pneumonia cardiovascular events (Di Bella); 23. reduces pneumonia-related mortality (Di Bella); 25. reduces lung invasion by monocytes and macrophages (Di Bella); 26. “lower hospital mortality, lower in-ICU mortality, reduced incidence of ALI or ARDS, and reduced” sepsis (Du); 27. reduced mortality in critically ill patients (L. Wang); 28. increases “lipid mediator 15-epi-lipoxin A4 restores neutrophil apoptosis and” helps resolve alveolar inflammation (L.Wang); 29. reduced mortality of Covid-19 by between 54% and 61% (Martha); 30. reduced IL-6, CRP, and macrophage-stimulating factor, thus reducing the cytokine storm (Martha); 31. reduced Covid-19 mortality by 44% (Wijaya); 32. reduces replication of coronavirus-299E and Middle East respiratory syndrome (MERS) (Wijaya); 33. demonstrates antiviral effects against “both DNA and RNA viruses including cytomegalovirus, varicella-zoster, rhinovirus, coxsackie virus, hepatitis C virus, H1N1 influenza virus, SARS-CoV and CoV-229E” (Wijaya); 34. reduces fatal thrombosis by reducing neutrophile extracellular traps (Wijaya); 35. major bleeding is not significantly increased by aspirin (Wijaya); 36. low dose ASA reduced Covid-19 mortality by 36% (Ma); 37. “aspirin use was not associated with bleeding risk” (Ma); 38. “protects from angiotensin-ll-induced organ damage” (Muller) 39. low dose ASA helped prevent “vascular dysfunction associated with maternal IAV infection” (Coward-Smith)                     

Naproxen (NPX) – direct antiviral effects: 1. NF-kBI, 6 times as strong as aspirin (Tanaka); 2.                               antagonizes the export of the nuclear protein (NP) out of the nucleus “by the host export                          protein CRM1” (Zheng); 3. works against IAV through multiple mechanisms “at both the                       early and late stage of viral infection” and “reduced the lung indices and virus titers”                                (Zheng); 4. “inhibited the replication of influenza A and B by blocking CRM1-mediated                         NP nuclear export”, “one of the key steps for the replication of influenza viruses” (Zheng);                     5. Inhibits N oligomerization (Terrier); 6. fits snuggly into the IAV RNA groove binding                        site, blocking replication (Lejal); 7. targets the IAV nucleoprotein and inhibits it binding                       (Lejal); 8. quickly reduces the viral titer by 93% compared to controls (Lejal); 9. of over                        100,000 molecules tested, naproxen proved most effective in inhibiting replication of both                      H1N1 and H3N2 IAV (Lejal) 10. NPX inhibits Zika virus replication “by potentially                                 reducing the expression of AXL, the entry cofactor of ZIKV (Pan); 11. “impeding N                                function associated with viral replication would be the main mode of action explaining the                     observed antiviral effect of naproxen” because “the N protein drives virus assembly and                        budding” (Terrier) 12. “naproxen might bind other viral targets such as the viral 3C-like                          protease” (Terrier)          

 NPX effects that retard respiratory disease pathogenesis: 1. “specifically inhibited viral                                       replication and protected the bronchial epithelia against SARS-CoV-2 induced damage”                         (Terrier); 2. prevents the cytokine storm caused by bacterial infection in the lung (H.Wang)                      3. inhibits interleukin-1b (IL-1b), IL-6, and TNF-a, and thus helps suppress the cytokine                         storm (H. Wang); 4. naproxen is more effective than aspirin in suppressing the cytokine                       storm (H. Wang); 5. is an anti-inflammatory that inhibits cyclooxygenase-2 (COX-2)                               (Lejal); 6. IAV does not become resistant to NPX (Tarus); 7. “is a potential broad, multi-                            mechanistic anti-influenza therapeutic” (Zheng)

As the mountain range of scientific evidence accumulated over the last 25 years makes clear, selenium, aspirin, and naproxen directly inhibit IAV replication though multiple, complementary, overlapping, and reinforcing cellular and immunological mechanisms. They are also effective a dozen different ways to improve oxygenation, reduce lung pathology, and help prevent clotting, organ damage, cell death, cytokine release, the cytokine storm, sepsis, septic shock, and mortality. They will reduce the incidence of disease sequelae including post-disease syndromes such as long Covid, and soon, the challenge and incidence of long H5N1. The evidence of their beneficial effects is unquestionable. It is impossible for an objective scientist to deny this because little to no evidence exists to contradict the obvious conclusion that these medications constitute both effective antiviral and anti-disease therapies. The only question that remains is why are national and international public health officials stuck in an outmoded paradigm that looks only to specific antiviral drugs that viruses quickly develop resistance to while they ignore broad-spectrum antivirals with their multiple mechanisms of action that can be used from day-one of infection? These three medicines are all safe, effective, available, affordable – and approved. They should be stocked as first aid in every home to use the moment people start to feel the unmistakable advent of flu – or Covid.

The CDC should institute a national program to educate people how to properly and safely use these medications instead of denying knowledge about what can help save people’s lives once the H5N1 or H5N9 pandemic tsunami hits. Falsely denying that treatments existed that could have been effective from day-one during the Covid-19 pandemic cost upwards of 800,000 American lives. That does not inspire confidence that that will not happen again. It is difficult for an institution to correct a mistake if they fail to admit their previous mistake. The self-serving, unspoken mantra of “new diseases require new drugs” should be discarded after reviewing the last two decades of science. Today we have no time to waste focusing on trying to develop new, expensive, imperfect drugs that are no better than those that already are sitting on pharmacy shelves that are approved and have already been tested. Early therapy remains the best therapy. It is past time to utilize the broad-spectrum SAN antivirals – before the HPAI H5N1 D1.1 tsunami sweeps potentially millions of American lives away. Obviously, vaccines are critical. But the first pandemic responders come in the form of long established and publicly accepted broad-spectrum antiviral medicines - selenium, aspirin and naproxen. The cost of a full course of SAN therapy is less than $20. To save a life from H5N1 would be $1,000 or less.      

As someone who has worked to improve therapy against pandemics since 1989 – AIDS, Ebola, Zika, Covid-19 and now H5N1 – I would work with anyone to help prevent the tragic episode of Covid-19 in which far too many Americans lost their lives, from occurring again with H5N1. As foreshadowed with the already demonstrated extreme lethality of H5N1 D1.1, the future case mortality rate may be much too high not to accept and quickly implement SAN therapy to save thousands of live in America and millions worldwide. There is absolutely no good reason to delay implementing this established knowledge as part of pandemic planning. Americans need to be prepared to face a viral pandemic much worse than Covid-19. Now. Not later.             

Scientifically yours,

Howard S. Armistead

Viral pandemic researcher since 1990