Have biopharmaceutical companies gone too far? As part of the $144 million publicly financed KidCOVE trial, Moderna evaluates its vaccine known as mRNA-1273 (Spikevax) on children as young as 6 months old while some trial sites report that 4 out of 5 of the young participants come from underrepresented/underserved communities (e.g. ethnic minorities, babies from poor households, etc.) This kind of data point troubles this author’s mind but so does the fact that our public health strategy needs to expeditiously pivo to therapeutic treatment.
The Devil is in the Assumptions
This author argues that there is little to no chance of achieving herd immunity if 100% of Americans including children are immunized with the current crop of early-stage vaccines. Underlying the dominant public health narrative today is the assumption that immunizing children will lead to herd immunity for everyone. That is because children (and the remaining unvaxxed holdouts are deemed the last reservoir of the pathogen). But assuming this vaccine is still experimental—which it is—is it ethical to use children as subjects in experiments to improve the health of adults?
Some argue whether there is more risk to children from the vaccines than from COVID. We know that the actual vaccine used in kidCOVE now is on the radar of several European nations that have halted or temporarily paused use of mRNA-1273 in young people. For example, all nations in Scandinavia have either put the vaccine’s use on people under 30 on hold pending more safety data. This is the case in Denmark, Sweden, Norway, Finland, and Iceland.
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Should Americans be paying attention to the movements in these countries?
Treatment for At-Risk Children
Most problems in children who died of the illness have arisen with those at risk. Those children could potentially be treated early with Regeneron or other monoclonal antibodies and fluvoxamine and soon with molnupiravir or Paxlovid. Based on data from the Together trial it is probable that a course of fluvoxamine would benefit all children to prevent long COVID and possibly multisystem inflammatory illness. Mast cell therapies may help as well.
Why Our Approach Feels Wrong
This author challenges the underlying premise that children represent the last major reservoir for SARS-CoV-2, the virus behind COVID-19. This challenge then applies to the premise underlying the declaration that children are thus “super spreaders.”
Sweden, a Scandinavian nation with 10.3 million people, did things a little differently. With 1.1 million cases they report 15,078 deaths according to Worldometer. The ratio of deaths per population is nearly double in America than that of Sweden.
Yet in Sweden, children went to school with no masks, no social distancing, no vaccines, and no drugs. They had no deaths and teachers were infected less than the general population. Is Sweden smarter? They have similar vaccination rates to us. They have 65% of the overall mortality rate of the USA but could it be because they allowed low risk people to get infected and develop natural immunity, at present their infection and mortality rates are less than a third of the United States? I fear that next the FDA will approve vaccines for 6-month-olds. Does this cross a line? Or am I just not seeing some bigger picture?
In my opinion, these vaccines have failed their initially intended purpose. Leaky Vaccines and virus spread.
As the pandemic ultimately moves into the “endemic” stage so will American society (and its medical establishment) move to rid itself of these vaccines while wholly embracing therapeutics. My argument: this will result in a country with natural immunity instead of a country with vaccine-induced immunity and high levels of infection.
Mass Vaccination vs. Comprehensive Treatment
The strategy of vaccinating everyone with these vaccines to prevent COVID looks less effective than a single IM injection of Astra Zeneca’s long-acting antibody, AZD 7442, which at 6 months had an 83% decrease in infections and no serious infections. The cost to treat everyone would probably be prohibitive. It is unlikely the government would approve it for everyone. They only have 6-months worth of data.
There will be a significant fee-for-service market for people who don’t trust vaccines and don’t want to rely on medications to treat them if they get infected. The effectiveness of ivermectin 0.4 mg/kg twice a week for prophylaxis needs to be studied. Studying those who decline the vaccines seems ideal. Unfortunately, because ivermectin is vastly overpriced in the USA at present, it would run about $72 a week for a 60 kg person. Long-term safety has not been proven.
This author posits that a reasonable strategy would be to treat people when they get infected. We need solid therapeutics available. Presently, three decent repurposed drugs are available. Fluvoxamine didn’t have enough data until Together led by Dr. Ed Mills, was reported 8/6/21 but there was plenty of reason for NIH to sponsor a large trial of ivermectin a year ago due to any number of data points including the impressive and proactive public health model in India’s Uttar Pradesh. Dr. Pierre Kory and the FLCCC testified to the Senate in December of last year.
Additionally, five articles implicating the value of famotidine and data from two researchers suggest mast cell patients on H1 and H2 blockers fail to succumb to severe COVID illness yet for many months the government chose not to fund large trials of ivermectin or famotidine. If ivermectin and famotidine had been tested and proven safe and effective during the past year there would have been much less morbidity. Since it didn’t happen and neither drug has positive large, randomized trial data, we are left in the dark. This author suggests that the NIH didn’t study these two low-cost, repurposed drugs for two reasons: 1) successful trials would have popularized these approaches. The vaccine rollout would have been much more difficult and 2) Not having repurposed generic drugs to contend with gave drug companies much more incentive to develop new therapeutics. After all, pharmaceutical companies face tremendous risk in developing new therapies and investors demand robust returns, or else.
The strategy with therapeutics may have deprived Americans of good repurposed drugs for therapy in the past year but incentivized drug companies who have come up with two new potent oral antiviral drugs, Merck’s Molnupiravir, a nucleotide analog, and Pfizer’s protease inhibitor Paxlovid. There is theoretical concern for cancer and birth defects with molnupiravir but Paxlovid looks a little more effective and has no obvious downside.
Marketing of Therapeutics Underway Already
Both companies are already marketing their drugs all over the world even though they are not approved yet Merck previously got a 1.2 billion dollar deal with our government. While Pfizer announced they are selling 10 million doses to the US for $5.29 billion and distributing it to 95 poor countries, representing 53% of the world’s population. With about 150,000 new cases a day, it would be enough to treat half the patients in the US for 134 days. Some people aren’t very sick and don’t seek treatment. Some seek treatment late. These drugs work best in the first 5 days when there is a lot of virus around. If every newly diagnosed patient were treated early, a major dent would be put in the pandemic. It is likely that those who decline vaccines would not object to taking an antiviral. With enough government promotion, people could be convinced to get tested and treated quickly. In my opinion, fluvoxamine which has unequivocally positive data and has anti-inflammatory activity should be given with paxlovid or Molnupiravir.
Yet Why Not Pursue the Others?
We already have fluvoxamine with a 1497 patient trial in Together with 31% decrease in admissions and mortality. One of the early-on financial supporters of fluvoxamine, technology entrepreneur Steve Kirsch, communicated that no one treated with fluvoxamine gets long COVID. We hope Together is compiling the data. Those who use famotidine and ivermectin report overall positive data points. All of them have reported to have value in already established long COVID but the drugs haven’t been formally tested. Despite this hardly anyone is being treated with fluvoxamine. Molnupiravir and paxlovid are being ordered by many countries and may get EUAs in the US while fluvoxamine hasn’t received little attention.
What’s the Science behind Famotidine?
Famotidine, the generic heartburn drug Pepcid, blocks H2 receptors on mast cells. Dr. Lawrence Afrin and others have postulated that mast cell signaling is at least partly responsible for cytokine storm. Dr. Afrin Mast Cells and COVID. He and Dr. Mariana Castells at Harvard have noted that their mast cell patients, all on H1 and H2 blockers never get very sick if they get COVID. 3 retrospective and 2 prospective studies of famotidine showed benefit. In one study, 10 patients were all given an average of 80 mg of famotidine 3 times a day. All were much better in 2 days with modest side effects. That research group will soon be reporting a randomized trial showing a statistical benefit of famotidine 80 mg 3 times a day. A nonrandomized trial of 25 consecutive inpatients, co-authored by Dr. Robert Malone, using famotidine 80 mg 4 times a day plus celecoxib showed significant benefit. 3 large randomized trials are starting.
Systematic Underdosing or Paranoia?
The response of governments worldwide to ivermectin has been disappointing, to say the least. The Uttar Pradesh data is ignored or discounted via fact-checkers that actually know little. The randomized trials are picked apart. Therefore, the jury is out until the 4 large, randomized trials are reported. Unfortunately, ivermectin-treated patients got or are getting 20% of the correct dosage in all 4 studies. How can you explain that Together gave patients 0.4 mg/kg for 3 days on an empty stomach when the correct dose for delta is 0.6 mg/kg for 5 days or recovered with food which increases blood levels 2.6 times? On top of that ACTIV-6(NIH), COVID-OUT(U of Minnesota) and PRINCIPLE(Oxford) are giving patients a lower dose of ivermectin than a dose that failed in a previous trial.
Multiple people involved in ACTIV-6 were notified. It appears there is a very good chance that patients will receive a reasonable dose of ivermectin. They have had over 3 months since the Together study was reported to do something. For 3 months patients have been getting placebo or a dose of ivermectin they know doesn’t work.
Over two weeks ago 6 editors in chief of important medical journals, the AMA, ACP and IDSA were notified about the ivermectin underdosing. No one wrote anything. Two editors in chief were asked to reach out to Oxford’s PRINCIPLE and University of Minnesota’s COVID-OUT to get a reasonable ivermectin dose used in their trials. If these trials use appropriate ivermectin dosing, ivermectin will have gotten a fair shake. Because of Merck’s conflict of interest with Molnupiravir and their attacks on ivermectin, a brand of ivermectin other than Merck’s stromectol should be used.
One has to wonder why none of the principal investigators of ACTIV-6, COVID-OUT and PRINCIPLE looked at Together and realized they needed to increase the dose or add an arm with appropriate dosing. Although it could be intentional, it could have been accidental. In Australia, Adjunct Professor Dr. John Skerritt, deputy secretary of the health products regulation group, who has a PhD in Pharmacology stopped GPs from ordering ivermectin 12 mg because he looked on the FDA site and saw that lower doses were used for parasites and feared GPs would poison people. Obviously, an unintentional move. Fortunately, he has been challenged by senator Gerard Rennick of Queensland who noted that doses up to 100 mg have been used safely.
In less than a year we should have 3 over the counter or generic drugs plus Molnupiravir and Paxlovid for therapy. This doesn’t include H1 blockers, and the many other mast cell stabilizing drugs, quercetin, luteolin, cromolyn etc. Regeneron’s cocktail of monoclonal antibodies (mAbs) cost $2100, require injection and will be less desirable. Some people may choose to pay for AZD 7442, knowing they are very safe for at least 6 months. We don’t know how these drugs stack up against each other and may never know.
I am concerned that trials of all therapeutic drugs for early COVID in the US will not be able to continue as is. It looks like paxlovid is likely to get an EUA soon. Newly diagnosed patients should be able to get it for free. They will choose not to enroll in randomized trials and risk being randomized to placebo or a less effective product. Trialists will face major ethical issues. Early COVID trials will have to study paxlovid vs. paxlovid plus something else. Fluvoxamine would appear to be the first choice to be added. For patients presenting late, the repurposed drugs will be important.
A Pragmatic Vision or Fools Dream?
Moderna developed a delta-specific vaccine, but it has not been adequately tested. ImmunityBio is working on a T cell vaccine. The future of vaccines is very uncertain. Since present vaccines don’t ensure that people won’t get infected or sick, I would think Americans would prefer the “if you get sick, you go to the drugstore and get some medicine” strategy. They would have to be confident that the medicine will shorten their illness, make serious illness extremely unlikely and eliminate long COVID. If Americans knew that they could get free, safe, effective medicine if they got sick and that if they took it early they would be fine, compliance would be high, hospital utilization and death would go way down and herd immunity could be achieved. Fear, which has been promoted heavily by our government healthcare agencies and the media, would drop dramatically and normal life could resume.
But NIH Swinging for Fences….
NIH gambled on experimental vaccine technology being a home run when no vaccines for coronaviruses had done very well in animals. Had they succeeded like in measles it would have been a home run but they didn’t. NIH hit a single, which kept the rally going but was not good enough to win against COVID. To effect their strategy they had to not study ivermectin and famotidine which might have been effective. Those drugs may have prevented hundreds of thousands of deaths. We don’t know. If they are subsequently proven to be of great benefit we will know. One has to consider that the FDA’s war against ivermectin is to prevent it from becoming known that it would have worked. Data on famotidine is coming despite our government. Fluvoxamine succeeded by being sponsored by a private citizen. Despite it working well in a large trial, our government ignores it.
Don’t Count out Pharma
NIH’s strategy allowed us to give the vaccines a fair shot. They just aren’t good enough in this author’s opinion. While they appear to reduce death and hospitalization the long-term prospect is uncertain for them. Perhaps they offered Pharma time to develop therapeutics? The drug companies came through. The combination of drug company therapies plus repurposed drugs should allow us to win against COVID in the long run. It might also give us time to go back to the drawing board and develop the kind of vaccines we really need. NIH will say the vaccines prevented many deaths and a lot more people would have died in the long run if the antivirals had not been developed. We don’t know what would have happened had famotidine, ivermectin, and fluvoxamine been rushed through like the vaccines were. If they had been rushed through and controlled the pandemic, the drug companies probably wouldn’t have developed the antivirals but then we may not have needed them.
At this point, the government knows vaccines long-term are not the answer and have embraced drug company therapeutics which look quite promising. The government spending billions on them isn’t such a big deal if they work and are safe. If the government can get most infected people to take the drugs very early, they will wind up with little serious illness, a lot of natural immunity, little, long COVID and a good shot at “herd immunity”. The caseload will drop dramatically in the US and government expenditures will eventually be modest. The benefit to the economy and the wellbeing of Americans—and others around the world–cannot be overstated.
A major risk is the virus developing resistance to the antivirals as happened with multiple AIDS drugs. Whether people should be treated with both antivirals to lessen resistance is unclear. The repurposed drugs which are mainly about mast cells and inflammation are very unlikely to be affected by viral mutations. Therefore, we must continue to study repurposed drugs which should add to the effectiveness of antivirals, are necessary for those not treated early, will be needed if resistance develops to the antivirals and will be crucial in the places around the world where the new drugs won’t be available.
Michael B. Goodkin MD, FACC