guest post by Leo Goldstein
[cr note: This is an interesting hypothesis from Leo Goldstein. I’ll add some observations]
We have a sharp surge in the new COVID-19 cases. The main [or just one factor out of several, a contributor ~cr] cause is likely to be the drop in the use of Hydroxychloroquine based treatment, following the FDA Memorandum of June 15. The FDA Memorandum accompanied the revocation of the Emergency Use Authorization for Hydroxychloroquine and Chloroquine from the National Strategic Stockpile. The FDA Memorandum vilified the drug, falsely alleging that it is not safe and “unlikely to be effective” against COVID-19 – when thousands of doctors have treated hundreds of thousands of patients with it . The National Institutes of Health’s NIH COVID-19 Panel updated its Guidelines to match on the FDA’s opinion the next day.
Although Hydroxychloroquine remains an approved drug and doctors can still prescribe it off-label, the FDA’s and NIH’s opinions have significant influence. State governments and medical boards adhere to the FDA opinion, in their subsequent recommendations. Even when HCQ is not banned outright, such opinion creates a chilling effect on pharmacies, doctors, hospitals, and, especially insurance companies.
From the declaration by Jeremy Snavely, 6/22:
Multiple members of AAPS have communicated to AAPS their inability to prescribe hydroxychloroquine (HCQ) for a full regimen to treat or prevent COVID-19, including but not limited to physicians in Western Michigan, Georgia, New Jersey, Arizona, and Texas.
Numerous physician members of AAPS, including this “Dr. John
Doe,” reasonably fear retaliation against them by state medical boards based on
Defendants’ irrational restrictions on HCQ along with the incorporation of the
directive made to state medical boards by the Federation of State Medical Boards.
(ASSOCIATION OF AMERICAN PHYSICIANS & SURGEONS v FDA et al, 1:20-cv-00493, FEDERAL COURT FOR THE WESTERN DISTRICT OF MICHIGAN)
It is important to note that early antiviral treatment of patients with COVID-19 symptoms, using HCQ + AZ (+Zn), benefits not only the patient, but the public in general. Such treatment quickly reduces the viral load in the patient and the chances of the further transmission. [While this may be the case, generally evidence at this time only exists for improved outcomes for patients~cr]
Fig. 1. US daily new confirmed COVID-19 cases per day, 7-day rolling average (*)
Fig. 1 shows that the daily number of new cases was declining in April and May, as many states were re-opening, then remained on the same level, despite an increase in testing. Even the riots and demonstrations that started on May 26 did not lead to visible increases. However, after June 15 the daily number of new cases shot up and continues growing.
Fig. 2. US tests per confirmed COVID-19 case, 7-day rolling average (*)
(*) The typical time between the infection and onset of symptoms is 3-5 days. Notice that the graphs are rolling averages, corresponding to central averages of 3-4 days before.
Fig. 2 shows that the number tests per a new case was steadily growing (getting better) from around April 16 to June 16. It has been falling after that.
The Game Changer
Yes, an early stage Hydroxychloroquine + Azithromycin treatment was the game changer in the fight against COVID-19. Fig. 3-4 shows that COVID-19 has never gotten much traction in Asia, Africa, and Australia, partly because of wide availability and absence of prejudice against CQ/HCQ in those regions. In March, most COVID-19 deaths were happening in Europe, and their number was growing uncontrollably.
Fig. 3. Daily COVID-19 deaths, 7-day rolling average (**)
But on March 16, Dr. Didier Raoult publicized his HCQ+AZ treatment regimen. Doctors in Italy and Spain started to use it, although slowly and only in hospital settings. On March 19, President Donald Trump “touted” it, immediately making this treatment popular in the world. On March 22-23, Dr. Zelenko published his protocol, adding Zinc, and, more importantly, stressing the need to treat early, without waiting for testing or hospital admission. Early HCQ+AZ treatment ramped up in Europe between March 21 and March 28. In Italy, it became the standard of care even for mild cases.
Some of the patients who did not receive HCQ+AZ treatment timely continued dying, with a typical two weeks between closing window for anti-viral treatment and the death. Those who received it, typically recovered. Around March 25, the growing number of new cases was matched by the growing number of HCQ-based treatments. This is reflected by the April 10 peak on the chart, which is an average of recorded deaths from April 3 to April 10. After that, the humans won, and the number of daily deaths went down.
The dynamics in North America was different. Governors of New York and Michigan, suffering from the Trump Derangement Syndrome, rejected the hydroxychloroquine, with heartbreaking consequences.
Fig. 4. Daily COVID-19 cases, 7-day rolling average (**)
(**) If a case outcome is death, this takes place on average 18.5 days after the symptoms appear. Assuming that the window for effective antiviral intervention is 4-5 days, a typical death happens about two weeks after the window closes. There was a significant increase in testing during this period. Notice that the graphs are rolling averages, corresponding to central averages of 3-4 days before.
Prevention of bad outcome of COVID-19 is not the only benefit of HCQ + AZ treatment. It also decreases transmission. COVID-19 patients are most infective within about 4-8 days since symptoms appear. The infected persons who have symptoms show them 3-5 days after the infection. Thus, an untreated “confirmed case” causes more symptomatic or “confirmed” patients 7-11 days later [this is hypothetical and not really known~cr]. This is how it worked until March 20, leading to the averaged peak of about 45 daily cases in the week March 26 – April 2. Then they ramped up the early treatment, immediately decreasing the viral loads and chances of transmission. Around March 25, they were treating enough persons early enough to decrease the transmission coefficient below 1. The continuous drop in the new cases, showing on the chart after April 7, is the evidence to it.
HCQ-based prophylaxis might have been a factor, too. Notice that shutdowns also occurred in the relevant time frame, and, probably, contributed to stopping and reversing the COVID-19 epidemic in Europe.
States that had low infection levels and used HCQ widely, like Texas and Florida, are especially affected. The daily number of new cases in Texas has quadrupled since June 15! Texas has largely reopened in May. Throughout the May and first half of June, the daily number of cases remained below 2,000. The FDA memo was followed on June 19 by a stronger worded statement from Texas Medical Association. (The current TMA leadership is militantly leftist.) The number of daily new cases went up and exceeded 8,000 on July 1.
Lacking legal authority to prohibit doctors from prescribing FDA-approved non-controlled drugs, some state governments used their ability to regulate pharmacies to cut patients’ access to Hydroxychloroquine. Surprisingly, the Texas State Board of Pharmacy was one of the first to do that. Its order said:
No prescription or medication order for chloroquine, hydroxychloroquine, mefloquine, or azithromycin may be dispensed or distributed unless all the following apply:
(1) the prescription or medication order bears a written diagnosis from the prescriber consistent with the evidence for its use;
(2) the prescription or medication order is limited to no more than a fourteen (14) day supply, unless the patient was previously established on the medication prior to the effective date of this rule; and
(3) no refills may be permitted unless a new prescription or medication order is furnished.
This “consistent with the evidence for its use” was interpreted as a permission to dispense hydroxychloroquine and azithromycin for COVID-19. It might be that this interpretation has changed to prohibition after June 16.
[Florida does not have such a leftist medical board and has been forging its own path~cr]
The high viral load in the population also increases probability of adverse mutations.
On July 3, Dr. Fauci said that the coronavirus mutated into a more transmissible strain. This is something expected when the only measure against it is social distancing. Such mutation might have been more important factor in the growth of cases.
Whatever the cause of the growth in the new daily cases, wider and early use of HCQ+AZ is a solution. [potentially~cr]
The FDA Memo, June 15
On June 15, the FDA revoked Emergency Use Authorization (EUA) for HCQ & CQ. This EUA was useless anyway. But it was accompanied by a memorandum, looking as science, but being anything but.
The FDA memo claimed 347 reports of adverse effects from HCQ in the context, implying these events happened in the US. It was based on HHS internal Review of Hydroxychloroquine and Chloroquine conducted by CDER Office of Surveillance and Epidemiology and delivered on May 19 (“the OSE Review”). This review was released to the public on July 1. It said that only 97 alleged cases of adverse effect were in the US, while 250 ones were abroad.
The efficacy of HCQ + AZ, with and without Zn, given early, have been reported by thousands of physicians around the world, and confirmed by more than a dozen of peer reviewed studies. The FDA elected to ignore them. It referred to all COVID-19 treatment regimens, using HCQ, as if they were one treatment. The FDA memo mentioned the British RECOVERY study, in which the researchers gave their patients a toxic dose (2,400 mg/day) of Hydroxychloroquine because they mixed up hydroxychloroquine with hydroxyquinoline. It also referred to the unfinished and not reported ORCHID trial (NCT04332991). This trial repeated old errors – HCQ was given to hospitalized (i.e., likely late stage) patients, with neither Azithromycin nor Zinc.
With the same logic, the FDA performed a literature review. The review was limited to the CDC library, thus omitting all studies not included in it. Even that was not enough. The FDA removed from the review the most valuable part – clinical trials, including randomized clinical trials. It limited the review to observational papers (called “studies of databases” by Dr. Raoult), including the infamous Mehra et al.
Contrary to the FDA Memo allegations, the OSE Review did not state that HCQ or HCQ+AZ combination is unsafe. The raw numbers suggest extraordinary safety of HCQ+AZ treatment. There were only 97 reports of adverse effects in hundreds of thousands of people treated with it.
QT prolongation was the most reported “adverse effect.” In fact, it is not an adverse effect, but a computed value, providing preliminary warning before an adverse effect, like Torsades de Pointes, arrhythmia, or tachycardia might happen.
The contra-indications for HCQ=AZ (including arrhythmia, tachycardia, and G6PD deficiency), and drug-interactions with strong QT prolongers (including some popular anti-depressants and anti-psychotics) are known and should be respected.
At the late stage, COVID-19 causes cardiac arrest in some of the patients. Apparently, when HCQ+AZ is given at the late stage, there might be negative synergy with the damage from COVID-19 in some patients. But the proper HCQ use is to start the treatment early.
OSE Review acknowledges the following limitations of its data (emphasis is added):
FAERS data have limitations. First, there is no certainty that the reported event was actually due to the product. FDA does not require that a causal relationship between a product and event be proven, and reports do not always contain enough detail to properly evaluate an event. Further, FDA does not receive reports for every adverse event or medication error that occurs with a product. Many factors can influence whether or not an event will be reported, such as the time a product has been marketed and publicity about an event. Therefore, FAERS data cannot be used to calculate the incidence of an adverse event or medication error in the U.S. population.
Doctors and pharmacists should disregard FDA/NIH/AMA/barking-dogs insinuations about Hydroxychloroquine. State governments should remove legal and illegal impediments to use Hydroxychloroquine in early treatment of COVID-19 patients.
[Additional studies are likely needed to develop this hypothesis such as correlating prescriptions per county to any changes to rising case numbers. There are scores of studies not being performed in this hyperpolitical environment, such as:
One: 65 plus year olds who take care of their grandkids vs those who don’t vs those who don’t have grandkids.
Two: studies of household transmission as a function of socioeconomic status, ethnicity, household size, house size.
Three: missed diagnostic procedures for various cancers, eg mammography, colonoscopies. Extrapolate delayed diagnosis to more costs, ie more advanced, and more deaths.
Four: Monthly death rates for the major classes of diseases from January thru now.
Five: adjudicated reviews of a sample of ‘covid deaths’.