@Grrry Creager: Glad it piqued your interest and we had hoped that a few dozen Intensivists and Pulmonologists would have, at the very least, made the same comments and expressed a modicum of concern for their failures to rescue their COVID19 patients that ultimately were prescribed “Comfort Care”, a virtual death sentence in an era of HMOs.
At the end of your article: "No one is safe until we’re all safe." A few years ago that meant that everybody had to get COVID vaccines for everybody to be safe. Is that what you mean?
The answer is more complicated than that, as things often are in medicine. In my experience, vaccines continue to play a very important role in preventing serious illness, hospitalization and death in the face of SARS-CoV-2. This doesn't discount the validity of infection-derived immunity, but recognizes that we're looking at a coronavirus with a short incubation period and a mucosal pathway initially. Cellular immunity takes a bit of time to initiate, so circulating neutralizing antibodies, derived from recent infection and/or immunization with periodic boosting are the only way we'll see circulating IgG. That said, we already know that there are immune cells that are primary sites for SARS-CoV-2 infection (an article highlighted yesterday on interstitial macrophage infection with direct implications for cytokine storm and further lung involvement in Acute Respiratory Distress Syndrome, suggests some answers to things my colleagues and I saw early in the pandemic with implications for oxygen and mechanical ventilation therapies.
But my comment is broader. We've seen a whole host of effective vaccines developed since the introduction of variolation in the 18th century to the Western world (practiced much earlier in other areas of the Ottoman Empire and perhaps China and India). There is a surge, since the pandemic, in anti-vaccine sentiment that is showing signs of becoming an issue in vaccine-hesitant portions of US society. To date, for example, 121 cases of measles have been documented to CDC in 17 States and New York City (reported separately because of its population density). Measles, unlike COVID, has a much longer incubation time. People vaccinated for measles have time for the cellular immune system to come into play and prevent the disease from taking hold. Of note, in this outbreak, over 50% of those diagnosed with measles have been hospitalized, most because of complications of the disease but some for isolation. Complications of measles include deafness and blindness, something a number of people fail to understand and where some with strident anti-vaccine positions frankly discount. 121 reported cases, so far this year, is already more than twice the total reported cases for calendar 2023. Of course, the 2023 total pales by comparison to 2019 (in excess of 1250) and 2014 (more than 600) but we're well on our way to a significant outbreak. Long-incubation viral illness with a known and effective vaccine are amenable to prevention with adequate vaccination coverage (estimated, for measles to require 95% population penetration for those who can take the vaccine and are not excluded for medical, usually immunodeficient reasons. This an example of where population immunity can protect an at-risk population unable to be vaccinated.
Another area, and one that's unpopular, involves masking when ill, and isolation when ill. Framed on the concept of a violation of individual rights, the proper lens through which to view this, in my mind and experience, is one of self-awareness of the potential harm that can be caused to others if they were to be infected from someone who discounted the potential effect of disease. Part of the problem here is related to businesses who want their workers working and present all the time, and they view isolation for extended periods as lost revenue and productivity, rather than valuing the health of their employees. The United States made, in my mind, an estimate when we did not follow the example of Europe where business owners and proprietors were paid by their governments to keep workers on payroll and paid, so they didn't suffer during the Pandemic. We, on the other hand, recommended closing areas of congregation without consideration of what would happen to people overall, and those considered essential were expected to continue to work with little regard for protecting them from potential infection. I suspect that, had the US followed a different path we might have seen less resistance to quarantine, masking, and vaccination requirements early on.
Rehashing the COVID-19 pandemic will be the work of myriad graduate students for decades to come, and of course, there are pundits who are already doing the same. It's likely we'll learn more in the long run from the graduate students than from talking heads who didn't have to study a portion and perform a truly scholarly analysis.
And, I'd be remiss if I failed to mention the adverse effect both misinformation and disinformation had on forming opinions around both the disease, and all the varied mitigation factors. For our purposes, disinformation is the spreading of known incorrect information for malign purposes, while misinformation similarly involves spreading incorrect information and data, but we'll suggest their purposes are more to spread their legitimate beliefs, even if they're unsupported by research and evidence. There's ample evidence to suggest several state actors were involved in disinformation campaigns; we can only assume their intent was to weaken and divide our Country in the process and they likely reveled in the deepening social and political divides over the origins, process and mitigations of COVID. Misinformation likely stemmed from people who got their news and information from closed sources that mirrored their preexisting views on politics and world events, and shared what they heard widely. Of course, we had some trained scientists and physicians who engaged in one or the other, and to be honest, I'm often not sure if they were misinformed, and subsequently pedantic, or actively disinforming their followers and patients. More's the pity.
This has been a longer response than I intended but, as I mentioned, the answer isn't straightforward, especially in today's divided culture and in issues surrounding COVID-19.
Thanks for your long response, which I learned from. I got a long response myself.
In 2020 I had a case of diarrhea that lasted 2 weeks. But no respiratory symptoms. Could that have been COVID? I didn't think so for several years until I read a doctor thought it was possible.
Regarding your event where 4 out or 100 people got sick, what's the definition of a super-spreader event? How many would have to get sick to fit that definition? At an event where you spoke about intrinsic medical knowledge to what was perhaps people in the medical field, I find it really strange that people who got sick refused to get tested. It's like they did not want to know if they had COVID for some reason. Any ideas on why they did not want to know? Maybe they could not got back to work right away if they had COVID?
I sure would want to know, as treatment for COVID is far more successful if it's started immediately after infection from what I know.
You wrote: "There's ample evidence to suggest several state actors were involved in disinformation campaigns:..." I'm interested in details about that.
When I was young there was no measles vaccine. I had 2 types of measles. At that time getting the measles did not cause nearly as much concern as it does today. With poor nutrition, measles can be far more serious. My understanding is that's why measles has caused far more damage in poor nations than in rich nations like the U.S. As you may know, a few anti-vax parents actively try to get their children infected with measles. They think life long immunity is better compared to getting vaccines, and there is another benefit from infection I can't recall right now.
In 2016 about 90% of children and adolescents had gotten the measles vaccine according to the CDC. Who is getting measles this year? Is it people who got the vaccine or those that did not get it? Do we know?
You wrote: "There is a surge, since the pandemic, in anti-vaccine sentiment that is showing signs of becoming an issue in vaccine-hesitant portions of US society."
I agree. This sentiment can be blamed on the high level statements about COIVD shots and the mandates. Mandates for shots that were new and had no long term safety studies caused resentment. When the shots were new, scared people crowded around and cut in line to get COVID shots. Only a few years later the majority of people stopped doing what the CDC wants, which is to continue taking booster shots. This is partly due to COVID subsiding and the lifting of mandates. Many people now view the risk/reward a lot differently than in 2021.
For those that got the shots initially when they first became available, how many boosters would they have received by now if they had followed all the CDC guidelines?
Negative side effects from COVID shots grew into a huge number of reports. We both probably know somebody who had a negative reaction, more serious than just a sore arm for a day or 2. The government downplaying and/or doubting those with lasting negative effects and offering these people no support brought about more doubt and resentment. Judges have forced federal agencies to release data on the shots and negative side effects.
I've followed doctors who initially liked COVID shots but later changed their opinion and now say the shots are bad, based on what they've seen with negative reactions. Their changed opinions about COVID shots spurred these doctors into looking deeper into vax science and its critics, and then becoming anti-vax when they were not anti-vax previously.
We heard a lot of messaging from high level health officials and the president that turned out to be not true such as "get the shots, and you won't get COVID or spread COVID." As you know, the president got COIVD after he had his shots.
You might say that the pharma trials showed that only a few people who got the shots also got COVID, but that's not the same thing as saying "you will not get COVID." People do not like lies being told to get them to comply with policies. The shots given during the pharma trials were not exactly the same as the shots given to the public, something that if known would have caused even more doubt.
Also, high level messaging reported as factual said that if only everybody would get the shots, then COVID would go away. "We must get COVID shots to every human on earth" became a policy proposal taken as very important and reported by media. This also turned out to be false in nations where almost everybody got the shots.
People who refused the shots were demonized. The chief editorial writer of the L.A. Times wrote we should celebrate the COVID deaths of anti-vax people. Being demonized motivated a lot of people to listen more to anti-vax sources.
The governor of California wanted to force all school children to get COVID shots, but he was stopped. He now has sort of apologized for some of his COVID policies, such as shutting down the schools for so long. All these things added up and resulted in more people doubting public health and vaccines. And maybe more people joined causes to defend their right to refuse vaccines for their children and themselves.
You wrote: "Rehashing the COVID-19 pandemic will be the work of myriad graduate students for decades to come, and of course, there are pundits who are already doing the same. It's likely we'll learn more in the long run from the graduate students than from talking heads who didn't have to study a portion and perform a truly scholarly analysis."
This needs to be done now, before people forget things they said and evidence and documents might disappear. Anthony Fauci has already forgotten things he should not have forgotten, unless he's lying.
@Doug Cragoe: As for your inquiry about 2 wks of diarrhea due to COVID19, I would venture to say yes, except you did not claim to have been ill otherwise prior to those 2 wks and no mention of testing for COVID19. Diarrhea has many causes, including dietary. Nevertheless, many various signs and symptoms that aren't severe can be a result of the virus. Even more receptors such as the neurotransmitter receptors a7nAChRs and attendant mitochondria are also affected and can be of serious consequences esp when associated with the blood vessel lining called the endothelium. Endothelial a7 receptors ares said to be a critical component for myocarditis, acute coronary insufficiency, new onset arrhythmias, biliary disturbances (GB disease without stones), as well as diarrhea.
There is a nice pictorial from Nature Medicine by A. Gupta et al July 2020 1017-1032, but I can't copy and paste here.
Thanks for your reply. At the time in early 2020 I don't believe COVID tests were widely available to the public. But even if they were I may not have got one, since I had no respiratory symptoms and or any other indications of sickness. In later years I wondered if there was any available tests to see if I had COVID in 2020. Since the anti-bodies fade with time, I learned that COVID anti-body tests done long after a possible infection could not detect that infection. But then I read about a test that could, but details on that test were impossible to get, and I don't know how accurate that test might be. Do you think it's possible for me to today get a test that can tell if I had COVID in 2020?
@Doug Cragoe: A brief search with the MS copilot returned this response that puts it in perspective. I agree with it (AI searches at this day and time are generally OK but not outstanding.)
“In summary, while antibody tests can provide insights into past exposure to SARS-CoV-2, they do not definitively determine immunity or predict future protection against COVID-19. ”
Early in the pandemic, many drugstores offered antibody testing and I thought it was a scam effort by commercial labs, because it was not definitive in any way, shape or form. It gave people the false impression they didn’t have to worry if they had antibodies, but did not understand the sequence of antibody production nor the timeframe. I did not use any of those test kits, and I suspected there were disclaimers, but that was often overlooked by the anxious Consumer IMHO.
Thanks for your reply. If I ever use an AI chat bot like MS copilot. I would want to use one that simply answered the question and not go on about why it think I asked the question. And if it did not know the answer, then admit it did not know the answer. My question was is there any test that could tell me if I had COVID in 2020.
AI chatbots have been shown to give false results. And they are known to make things up that are false. It's called hallucinations. The makers of these AI chatbots don't know why they make things up that are false.
I use search engines because with them I have an idea of where the information is coming from and can make my own judgement as to the validity of the writing. I can also check other websites. I asked the question here because this substack writer has some knowledge in this area and I was seeking an informed opinion. I just did a quick search and found out these anti-body tests are not very accurate, and anti-bodies generally only last up to a year after COVID. So I will likely never know if I had COVID in 2020.
That's quite an experience in your "super-spreader" event. (no offense or pun intended). I am now a retired MD having been involved with every phase of this pandemic since early 202O. When I was working in a post-acute care unit (LTACH caring for ICU-type patients) we were asked to "please do something" by patient advocates, most being a spouse, child, sib, etc. Not many physicians. Why? Because they already did "all we can do" and dutifully prescribed all the official EUA protocols. Much to their surprise not all the victims responded the best available - dexamethasone, MCAbs, remdesivir, tociluzimab and the like. Many victims required ventilators, hi-flow O2 and sometimes dialysis when things went south. It was deemed inappropriate, in fact, job-terminating to Rx anything but official protocols whether the first round or the last round and the patients were deteriorating, nonetheless. The LTACH team got the worst of the worst cases and had no precedent therapies to offer. Yes, some of these same patients got HCQ and ivermectin, but often surreptitiously - mostly pre-hospital, and showed, not unexpectedly, zero benefit. Some were prescribed HCQ and ivermectin in later stages and coincident or not, had more complications - cardiac, renal and hepatic among them. So, in the LTACH a novel therapy was provided after consultation with families grateful for something that might help with little risk based upon decades of experience with an FDA-approved drug used world-wide and with a well-studied safety profile for victims of the disorder sickle cell disease. So what's the problem prescribing a drug restoring vital cellular dysfunctions and physiology gone amok for disorders demonstrating the same dysfunctions as progressive COVID19? Rigidity, adherence to EBM without regard to patient advocacy or a novel scenario demanding a different approach - recall the definition describing a repetitive procedure and getting the same negative results). Well, the drug is still being prescribed, mostly in the outpatient setting since the number of hospitalizations has plummeted this past 1-2 years. A diminished patient pool greatly reduces the incentives to get large studies of patients willing to participate in a funded study. Try getting funded for a study using a repurposed, generic drug even if there are NO adverse consequences for a 5 day course, no economic disincentives, and consistency for a positive outcome in hours to days, not weeks, mos, or in the case of Long Covid, years. I am not promoting misinformation. I am promoting common sense and patient advocacy. There are basic principles of scientific discovery deeply entrenched with this approach. Efforts to alert the FDA, NIH etc about the clinical outcomes have fallen on deaf ears. We are not conspiracists. We believe it is all intertwined with the politicized and misinformation campaigns by proponents of HCQ and ivermectin. Repurposing has been poisoned and there is little to no ROI potential for commercial purposes. Long preamble Dr Creager but your colleagues are part of the barriers we have encountered. Disbelief in any and all scientific approaches to prevention as well as therapy and therapeutic research has been stymied by rigid minds and adherence to EBM despite the consequences of premature death or prolongation of multisystems dysfunction. Among those consequences are post-Covid cognitive issues, cardiac arrhythmias appearing months after Covid19, myocarditis, renal disease, pulmonary fibrosis, etc. Your colleagues, like it or not, vaccinated and/or boosted, are deniers and little can be done to make them see reason as long as they have closed minds. That includes physicians and nurse practitioners, in our experience. 6 prescribers in our area can attest to helping nearly 2,500 patients to date. As you stated, Covid is still around, it's not seasonal but it continues to get a boost when people gather and are exposed to others with "cold/allergies/ tickle in the throat" issues. The issue with Paxlovid is its basic pharmacodynamic - it's an antiviral, pure and simple. As for efficacy with the newer variants, it's not at all surprising that it's not as effective for symptom control acutely or for the long term, ie LC/PASC. Our own clinical experiences and increasing knowledge about the virus' mechanisms of action is now going into its 5th year. The basic science, immunology and epidemiology has become increasingly more clear because we have approached this disorder with an open-mind and are willing to share what we have learned with like-minded (open-minded) persons. In the case of the 6 prescribers, they are unique as they are true patient advocates and not beholden to rigid protocols. Treating with a pure anti-viral in the early stage of replication is simply not enough. The virus has invaded and disseminated soon after exposure. If you test too early and it's negative, there is a false assumption that "it's not COVID19", and Paxlovid isn't appropriate according to the PI. If you wait until you are at your worst your test may again be negative. Testing for the antibody status to determine whether you did or did not have COVID19 isn't consistently helpful. If you have felt un-well for weeks to months and your IL-6 and TNF levels are elevated it supports the contention you had COVID19, but what then? There is no approved therapy at that point. Paxlovid data does support the fact that you greatly reduce your risk for being hospitalized acutely and likely won't die, but it doesn't address the risk of continuing PCC/PASC issues. Repeated COVID19 raises your risk of a PCC/PASC/LC scenario. Google or do an AI study (or 3) to read about a7 nicotinic acetylcholine receptors and COVID19, hydroxyurea as an immune modulator, and the anti-idiotypic antibody network as related to Long Covid. You will learn much. I have. It's ongoing. My biochemist/immunology colleagues have ongoing experiments clarifying the mechanisms and the targets for this disorder. Let the naysayers keep on denying. There is a pervasiveness and unwillingness to understand the how and why. Ok, I'll end my rant there. I feel for you and I appreciated hearing about your experience. It's only one of many I've heard for the past 4+ years. The controls are the colleagues with which you gather and those that chose no Rx vs some Rx. A most impressive scenario I was privvy to was the case of 5 healthy 40-70 yr old men working in a Federal capacity who gathered in a small restaurant for a long lunch, all 5 came down with the Delta-era COVID19, all were hospitalized (when hospitals were inundated with COVID19 victims), 1 (a twin 70 yr old) took 2 tabs of HU on the way to the hospital, his brother declined the HU. The other 3 declined HU and were put on vents within 36 hrs. The Rx'd twin's O2 sats in the 70's climbed to 90 within 12 hrs so he was discharged. His twin and the other 3 were dead within 10 days despite "official protocols". Coincidence? Luck? Bad karma for the dead? Do you try a little harder when the official protocol isn't helping? I sure would. I could tell you dozens of other similar stories. Again, the key to the disorder in our experiences and research is the ultimate targets and the host antibody response. You won't get better with a slug of decadron (one such Clinic locally is currently reportedly treating Hispanics by fraudulently injecting decadron @$700 as a COVID19 cure) or the infusions of remdesivir, or MCAbs, as has been shown for all but the archival strains. Paxlovid is a stop-gap with limited benefits, mild-moderate ADR's, non-durability in some cases, but a very very lucrative one at that. HU cost for 5 days? $5.90/10 tabs. It's a complicated disorder and it's ongoing. The public deserves better. Molecular screening and mining EHR's takes years and personnel. When NaCl and O2 by mask turn up as the #1 and #2 therapies for COVID19 on the CDRC/Cure ID website after screening on the massive scale, you know that a bureaucracy is in charge, but it's a fact and I/we are saddened that our ~500 case reports of a viable/credible COVID19 therapy have been totally ignored by the FDA. Close-mindedness again.
You provide a LOT to unpack here. I'm still looking at case reports and the rare published clinical trial for HU in COVID-19, and the results are "interesting". I'm having trouble envisioning the biochemical pathway to improved efficacy of HU however.
As for the use of a variety of treatments off-label, my colleagues early in the pandemic were "just doing it" if we saw something that showed promise in the torrent of literature that was coming out. Trials were not randomized but they were coordinated in-house. Management (bean-counters) were rarely involved. Our experiences with HCQ and ivermectin were uniformly, and rapidly bad, so they were abandoned early on. To the best of my knowledge, no one suggested HU in that timeframe.
@Dr Creager: I do appreciate your willingness to dialogue here or privately as you wish. Few physician/scientists seem to have any interest in a potential "sleeper" like hydroxurea (HU) since it is invariably associated with oncology and the PI lists dozens of POTENTIAL ADRs. (Read a PI for COX2's or other NSAIDs and be equally frightened I've told patients). I've yet to see ANY comments about HU's life-altering benefits for sickle cell victims or positive comments about HU safety or utility in SCD from Hematologists in any of the many interactions I've had online over the past 4+ years. Much is known about the pathophysiologies of SCD and only the casual reviewer will focus on abnormally shaped RBC's with attendant micro-vascular occlusions as the single cause of a sicklers grief from generalized pain, thromboembolisms and opioid addictions. The disorder is far more that genetic derangement of the red cell membrane. It's also a system disorder. Multisystems inflammation with associated vasoconstriction, endotheliitis, and tissue hypoxia are significant derangements in SCD crisis must be addressed. The quick and dirty fix for the suffering SCD victim in crisis is hospitalization for IV fluids, morphine, blood exchange transfusions to "dilute" the crenated/sickled cells made worse under the circumstances of the acute inflammatory processes but these modalities merely deals with the crisis temporarily. HU is the mainstay drug for the Hematologists preventive therapy (until the CRISPR gene-molecular editing is a reality for real-world cure) and HU been approved as a safe and durable therapy for decades even advocated for infants at 9 mos of age over a life-time. The literature on HU and SCD provides much basic science and provides a foundation for appreciating some of the same pathophysiologies of inflammation, vasoconstriction with the role of NO in mitigating the tissue hypoxia. I have many references on file after nearly 5 yrs of study. Then there is the new found evidence from the lab. The unique experiments designed by our collaborators defining the role of HU in relation to the viral-host ultimate targets we believe to be a key in understanding the cellular biology and immunology of the disorder COVID19 and possibly PASC. You mentioned difficulties finding articles about HU and COVID19. It's helpful to "buy into" the concept that COVID19 is indeed an immune disorder precipitated by the SARS-Cov2 viral-host interaction and the targets are critical molecular structures right from the first exposure by a susceptible host (includes vaccinated and unvaccinated). Perhaps you located the PISCO trial on ClinicalTrials.gov. It was a Mexican trial relating pyridostigmine for treating COVID19 and was addressing the a7nAChRs but never was completed for unknown reasons but I suspect it related to funding or expertise for analyzing the outcomes since there was no f/u data was never ever submitted to the ClinicalTrials. My attempts to contact the corresponding author were futile. Otherwise, I am not aware of a single published human trial with HU or pyridostigmine. We contend that HU as an immune modulator must initiate any therapy addressing the immune-disabled targets, the a7Rs, prior to treating the neuromuscular pathophysiologies in severe/advance COVID19. That was our experience and we published case reports describing that rationale. At the time we only had a few dozen patients but as time passed many more were treated both inpatient and outpatients having no precedent therapies to offer COVID19 victims. I am gratified to know that others had similar misgivings (and a horror) for doing nothing and recognizing the futility of the HCQ/ivermectin claims. Perhaps your alternatives were being used before the availability of the EUA protocols or possibly after the EUA protocols failed? Or were alternatives used in conjunction with the EUA protocols. Perhaps your hospital leadership recognized that as physicians you and your colleagues were using intellect, expertise and advocacy for trying alternatives. Did you get any negative feedback or outright threats for using "unapproved COVID19" therapies? I can tell you many horror stories from our experiences. HU was the 1st and only plausible drug that popped up into our collective consciousness - the medical LTACH team. The lead hospitalist had hematology experience, a working knowledge of basic cell biology and physiology/immunology and was familiar with SCD crisis management. The principle derangement that was being addressed is tissue hypoxia. In the case of progressive COVID19 as well as sickle crisis, it's multisystems inflammation, etc. The first LTACH patient responded promptly to the HU. Subsequently pyridostigmine was added to a vent-dependent COVID19 victim (long since PCR negative upon admission to the LTACH) since it was an antidote for reversing the toxic effects of vercuronium, the paralytic necessitated for the patients repeatedly "un-weanable" vent tethering in the acute ICU before his "last ditch" referral. Subsequent to a brief course of HU, NG-oral Mestinon was cautiously titrated up and the patient "rose from the dead".
For 3+ years we have collaborated with a team of Biochemists, Physiologists, Immunologist who have published for decades and their knowledge base for a7Rs seems unlimited. This basic cell biology expertise with the a7Rs was the reason I made contact and introduced the concepts for our clinical therapy with HU in COVID19.
I'll be following up. I've been busy of late (will explain in email, you will chuckle). And thanks for the references. I'll start looking at the ones I've not already found.
The group I fell into recognized early on that SARS-CoV-2 was not creating a "normal" ARDS/pneumonia, and started trying other tricks. We'd tried steroids at various dosages, as did other groups, but too early in the course of the disease, and often as a last-ditch measure. And we went away from steroids. Imagine our dismay when dexamethasone in week 2 of the course of illness was found to be effective... and at nearly trivially low doses. We tried the antivirals, and even some anti-retrovirals. To no avail, although there's new research suggesting some of the anti-retrovirals may hold some hope for treating Long-COVID based on a couple of preliminary reports. Mostly, we ended up focusing on delaying intubation and controlled mandatory ventilation for as long as possible, preferring, instead, the non-invasive approaches. Our mortality improved enough to move the needle but early cases, and case fatality rates, were grim regardless. Exposing an immune-naive population to a novel viral agent with a high affinity for human cells had significant consequences.
Our group was one of the first to recognize SARS-CoV-2 as a vascular disease, but it took us a bit longer to recognize this was likely an immune response. This was because autopsy analysis actually found evidence of replicable virus in atheromas, suggesting either an affinity for cholesterol-rich environs, or were clustering in damaged microvascular sites and attracting fatty depositions. We suspected damaged vasculature might have more cells with ACE2 receptors due to the damage but never went beyond hypothesis. In retrospect, an immune-mediated response in the microvascular space makes more sense, but still fails to explain the collections of replicable virus.
One benefit we had was that there was never mention on our chats of hospital leadership getting overly involved. In all three institutions, the clinicians had pretty free reign, limited mostly by what the pharmacy could provide: It was hard to get additional supplies by then if we came up with something really hare-brained. Of course, I was not clinically involved, but no one ever said, "Administration told me no". I should follow up with the folks from the past and see if that became an issue later, or if they were simply left alone.
Our paper describing molecular biological mechanisms for repurposing hydroxyUREA as a credible therapy for COVID19 was just published for all to see. It is our fondest hope that it will alert appropriate clinical research entities (preferably un-affiliated or beholden to big Pharmas) to delve into these heretofore un-described concepts linking the a7nAChRs as the targets for the viral-host-immune response and the role of HU as the preferred therapy as an allosteric immune modulator described exquisitely by Ben Mofftah & Eswayeh pharmacologists as well as the team of Biochemists with whom we have collaborated for over 3 yrs. Our consistently positive clinical experiences using HU as a novel repurposed therapy for severe COVID19 victims have been translated into a unique series of experiments leading to this and other original discoveries about SARS-Cov2 and host mechanisms. As for mortality during the peak of the pandemic without HU it was significant (~25%) but even 2 doses of HU appeared clinically to interfere with the virus' invasiveness, dissemination, endotheliitis, hypercoagulation, and progression to ARDS scenario. Controls were groups that had a common source and declined any therapy (none available until Paxlovid arrived anyway) and active therapy with the HU protocol. NONE that took HU progressed while many (can't give a figure) that declined HU were hospitalized and some of them died within 10-14 days. The rural city of Thomasville NC was especially hit hard as many died of COVID19 and related disorders. Case Reports numbering nearly 500 entered into the CDRC/CURE ID system provided some documentation for the oversight management of the FDA, that chose to ignore any and all of these consistently positive clinical outcomes after taking HU. Aside from HCQ and ivermectin, few other credible RCTs were supported by any clinical research entities and none showed convincingly positive outcomes, aside from Pfizer's pure antiviral Paxlovid.
Ref: Ben Moftah M, Eswayah A. Repurposing of Hydroxyurea Against COVID-19: A Promising Immunomodulatory Role. Assay Drug Dev Technol. 2022 Jan;20(1):55-62. doi: 10.1089/adt.2021.090. Epub 2022 Jan 6. PMID: 34990284
No question or random neural firing is off-limits. 😉
As for inquiries about lab techniques, reactants, lab equipment I would have to plead je ne sais being only the pure clinician with medical science gleaned over many years of patient experiences and 5 yrs delving into COVID19 related research topics.
Thanks for your candid remarks. I look forward to further discussion. Our experiences with administration and unit leadership in our host hospital was nothing short of abysmal. Despite a high ICU mortality in the 25% range, the official protocols remained the only game in town in the acute setting. Our lead Hospitalist worked in both the acute ICU as well as the LTACH being officially employed by an ourside Hospitalist group. He saw first hand the failures in the acute setting and even when the early successes from the LTACH experiences were evident, there was no effort to examine those successes or change the EUA (heavily subsidized, I would venture to add….) protocols. The threats to his job security were not subtle at all. Do as we tell you, in essence. Kudos to your administrations and pharmacy for supporting your efforts even if they were not as successful as ours. I view the successful outcomes with the introduction of the Decadron as somewhat serendipitous in the sense that studies showed benefit at that stage of cytokine activity driving the O2 demand higher and higher and mechanical ventilation a necessity over Hi-flow or BiPap O2 support. The cytokine response for most critically ill patients was such a red flag that it’s difficult for me to envision not using a steroid in that setting. Given the utility for reducing brain edema after brain surgery, it made sense to use decadron over hydrocortisone as I view the scenario. I was not clinically active during this pandemic. I am simply being the arm-chair QB and using that ol’ retrospectroscope. My role was to assess the proposed novel therapy by our clinical team fbo post-acute advanced COVID19 victims and provide input as to the credibility for using HU in this setting without the benefit of those EBM and highly powered RCT’s in such an emergent scenario. It made sense to the entire team as well as 2 consultants such that they have continued to support the role of HU based on their own personal and professional experiences with the drug - even after 5 yrs of clinical use. They made the effort to review those novel experiments devised by our International Biochemistry/Immunology collaborators under our clinical directions demonstrating the how and why of our consistently positive outcomes. We have yet to convince any entity to repeat the published experiments or contemplate trials. The window of opportunity for these trials has closed, I fear. Fewer advanced COVID19 patients and more infected people choosing to “take their chances” that the “cold symptoms” aren't so bad and the mindset that only those with advanced age or co-morbidities will suffer with PASC consequences. Paxlovid has its limitations as a pure antiviral in our view.
There were some institutions where heavy handed administrations took hold. I was not personally involved clinically, but was invited to join a gaggle of clinicians from at least 3 major institutions mostly in the West. I suspect their various administrators didn't meddle much in the early days because they were too scared to show up on the wards and in the ICUs, but I heard no suggestion that anyone was meddling.
Our discussions of steroids early were meant to try to stave off the cytokine storm we were seeing in patients. And early, we saw this in the first few days of hospitalization, but in retrospect, that was likely 7-10 days into the illness because people were presenting so late, and were so debilitated that high-dose steroids didn't help; in those who were not that far along, steroids likely muted their initial immune response, reducing available humeral antibody production and reducing their chance of dispelling the virus. In other words, while timing was everything, we had no really good handle on the timing to administer steroids, even though it seemed obvious that was going to somehow be useful. Our teams adopted decadron hesitantly because we'd already tried steroids and our results were mixed... at best. But once our clinicians understood the timing requirements, we embraced it.
Your results with HU are interesting. I want to offer that the reticence to look at your results could well have been colored by the scandal engendered by Didier Raoult and his claims of broad success with hydroxychloroquine that were not reproduced in any subsequent study, including several that are still theoretically underway. His claims poisoned the well for a lot who might have otherwise revisited the repurposed drug arena. I'm not sure what he hoped to accomplish but several large-scale studies attempted to reproduce his results and were terminated for futility and increased mortality. That was unfortunate.
I agree that we're likely to see fewer advanced COVID-19 patients in, at least, the near term, but I remain concerned that we're no more than one significant 40-base variant away from another significant peak. On the positive side, enough people have been infected to date, with or without the vaccine, that they likely have trained up the cellular system to recognize S1, as well as nucleocapsid antigens, so the cellular response will be stronger. This doesn't preclude significant cases in immunocompromised individuals, nor in those who are infected with an extreme viral load, but hopefully we will be spared the difficulties of 2020 and into 2021. As you note, too many are discounting the virus' capabilities as a multi-system agent. Our little discussion group began referring to SARS-CoV-2 as a vascular actor by no later than July once we started understanding the impact on lung tissue... and the fact that we were not dealing with the same acute respiratory distress syndrome we were used to. We saw more barotrauma in unaffected lung, found that we were less able to recruit affected alveoli with PEEP/CPAP, and that residual alveolar fluid seen at necropsy was closer to a gel than a liquid (one pathologist described it as an aerogel rather than a liquid). Vascular changes in the alveolar capillary bed were also seen, contributing to microclotting, and this correlated to microclots in solid organs and distal vasculature. What was curious from that was that we saw few real pulmonary embolic phenomena, but that strongly suggests this was acting more on the arterial side than venous. I never fully sorted that out in my mind. That will remain a topic for graduate students and MD/PhD students for a generation.
The American public has gotten over this virus, but doesn't seem to understand that the virus is still around and still looking for ways to reproduce. Until it settles into a ladder-like mutation scheme, the random mutation pathways will render us vulnerable. A lot of effort has to go into PASC, and we need to restore faith in the Public Health community, as that group (and I tend to drop myself in there) did a pretty good job of meeting and understanding the virus and pandemic, but we failed in our attempts, for the most part, to communicate what we knew to the public, and even when we had sufficient time to talk to decision makers and answer their questions. they often went looking for another position or opinion that better fit their preconceived notions. Too often, they found those in social media or "news sources" that were not playing with all the info, or worse, were manufacturing information for the purposes of explaining things as they best understood them (without the benefit of clinical and educational experience), or worse, with an intent to mislead. I saw this too many times.
As for PASC, in our concepts and the research of Dr. Maryna Skok, the basis is the immune response to the virus gone amok and it's a consequence of the anti-idiotypic antibody network - the antibodies to antibodies. Therapy should begin with an immune modulator, specifically, HU that restores the function of the a7Rs. My colleague has some early limited therapy experience with a brief HU course followed by a low dose titration of the more centrally acting enzyme inhibitor Exelon approved for AD having much the same pathophysiologies involving the a7Rs. You might say that AD is the proxy disorder for Long Covid brain fog as we envision the multisystemic pathophysiologies of Sickle Cell crises the proxy for COVID19. They both respond to the ACh enzyme inhibitor.
Dr. Skok's paper on a7Rs and PASC:
Skok M. The role of α7 nicotinic acetylcholine receptors in post-acute sequelae of covid-19. Int J Biochem Cell Biol. 2024 Jan 11;168:106519
With regard to our clinical approach treating Covid , we were dealing with post-acute ICU patients that were aggressively managed with the usual approach for any progressive respiratory failure. Like The clinicians in your arena, steroids were used Liberally and much like a shotgun approach. As you described, often it was too little too late or too much too soon. Steroids were parsed for individual scenarios. Various intravenous, antivirals and immune globulins were used as well as diuretics, and often antibacterials were added. It was all hit and miss. As The EUA protocols appeared things didn’t change a whole lot But there were suspicions that drugs like remdesivir were adding insult to injury, especially in the cardiac and renal areas. Many of the physicians started getting used to the increased mortality. Burned out with all the death and dying, and a sense of futility or what they were doing, but they wouldn’t admit it and administrations wouldn’t let them try other things. Those patients that had more aggressive family/advocates and physicians that heard about our successes, began the referral process in that early stage of 2020. In the post- acute LTACH setting, there were no precedents for therapy of COVID-19 so we had to dig deeper. Our lead hospitalist focused on the fact that some patients came in with low oxygen saturations, but a relatively Mild ARDS picture, coupled with declining respiratory parameters. Also there was evidence suggestive of significant respiratory muscle fatigue. Tissue hypoxia was quickly adopted as a Target and with his experience taking care of sickle cell patients, being from the eastern Mediterranean area, he raised the issue of using hydroxyurea a mainstay for SCD. We immediately did some in-depth reviewing of The pharmacology and physiology having been well-studied with sickle cell disease. Hydroxyurea met all the criteria, and it was decided that a trial course of five days would be reasonable and safe. Many of the patients came in with elevated white counts as one would expect with a viral or bacterial pneumonitis so a slight diminished white count after 3 to 4 days was not deemed worrisome, but a reasonable response. Well, it wasn’t just the white count that diminished, so did the oxygen demand, the respiratory settings declined, respiratory effort was improved, and the patient’s entire picture changed in just a matter of 2 to 3 days. We knew we were on to something. One particular patient came in with a particularly bad picture and weaning was a real challenge, even after a few days of hydroxyurea. It turns out he probably was a slow metabolizer of vercuronium , A curare like paralytic enabling him to stay on the ventilator without violent resistance. He had failed multiple weaning attempts in the acute ICU, and we were charged with trying to wean him, given our good experience in that realm over several years. The antidote for the vercuronium toxicity was pyridostigmine. Within hours his scenario showed dramatic improvement starting with eyelids, ocular motions, improved swallowing, cognition, respiratory efforts, etc. The AChEI was titrated up and then down until he was able to be extubated and his clinical picture became so much improved. Thereafter it was felt that a cautious trial of the same AChEI might benefit other post acute Covid patients, and indeed the rehabilitative efforts were greatly shortened. Patients with multiple chest tubes to drain effusions, residual fevers, renal dysfunctions, cardiac arrhythmias, all showed striking improvement with a short three day course of the HU followed by titration of the ACHEI. During that time, I was doing the research on the a7 receptors and found the expertise in an unlikely place, Kyiv, under siege by the Russians. One of the biochemists also a molecular biologist, immunologist responded to my inquiries and we developed a collaborative relationship thereafter. She is the corresponding author on that recent paper on several papers as I noted on other comments. Additional studies have been performed and are in publications. She had planned additional collaborations with German electrophysiologists with whom she had worked in the past. Sadly, on April 11, she had a sudden death, possibly “a clot or MI” and I have yet to hear what will become of our momentum. We are all at a loss at this stage. Large scale studies and comparison trial are needed but with the significant decreases in hospitalizations and acute infections the window for that may have closed (temporarily). Anecdotally (on top of anecdotes!) my Hospitalist colleague has continued to treat outpatients who have heard of him word of mouth or were treated 1 or more times in the past with other variants. He also believes that Flu A & B respond to his HU protocol since many signs and symptoms point to the same a7Rs as targets so this type of PAM2 allosteric modulator HU is effective for those viruses as well. “They do very well with 5 days of HU” he declares.
My suggestion: do what the HCQ/Ivermectin doctors did. Create your own website about HU treatment for COVID. Include your dosage level, when to use it, what drugs or treatments work well in combination, scientific studies, how to contact you for questions. Don't try to go through the system anymore, go around it. You might increase knowledge of your treatment and more doctors using it. You might use it to raise money.
You wrote:
"Repurposing has been poisoned and there is little to no ROI potential for commercial purposes." I think repurposing was poisoned long before COVID. Big Pharma has an outsized influence on top medical journals and federal regulatory agencies. Eliminating the competition is good for business. Pharma is the biggest spending lobbyist category in DC by far and has a revolving door for high level regulatory officials that retire and then go to high level executive position at Pharma companies, and vice versa.
Funny how your complaints about the medical system are very similar to those that came from the HCQ/Ivermectin doctors. Example from your post: "It was deemed inappropriate, in fact, job-terminating to Rx anything but official protocols whether the first round or the last round and the patients were deteriorating, nonetheless." This happened to HCQ/Ivermectin doctors who were fired and lost academic careers. One of the top advocates for Ivermectin was out front in 2020, advocating for the use of corticosteroids for COVID treatment. The entire world medical system including the WHO was against it, and said he was wrong. But within a year a corticosteroid -dexamethasone - became widely adopted and standard practice.
@Doug Cragoe: Another point about my own website relates to some of the folks that tout HCQ/Ivermectin. I do not want to get lumped into that sort of hype. The most egregious example is a physician named Kory. Surely you've heard of him. Touting ivermectin for prevention, active infection, lingering infection and when all that proved to be bogus, he went after the vaccine ADRs and characterized the ivermectin almost as an antidote "for those horrible shots". His website gives you more insight into the motives. For a mere $350 he will consult with you and give you an RX for his wonder drug. Discounted if you speak with his NP. I've heard that he also took it as a weekly preventive and got a bad case of COVID. He recovered and I have a pretty good idea what he was given and it wasn't ivermectin or HCQ . No, I want to have a credible presence and a clinical confirmation from researchers that buy into our 5 yrs of research and sound pharmacology principles. The numbers of infected people are lower and fewer are hospitalized currently , but I do think this coming Fall we will see another variant and those number won't remain low. Recipients of HU have all been pleased with the rapidity of response, the durability, absence of side effects and low cost.
I'm a Dr Daniel Griffin fan.
@Grrry Creager: Glad it piqued your interest and we had hoped that a few dozen Intensivists and Pulmonologists would have, at the very least, made the same comments and expressed a modicum of concern for their failures to rescue their COVID19 patients that ultimately were prescribed “Comfort Care”, a virtual death sentence in an era of HMOs.
At the end of your article: "No one is safe until we’re all safe." A few years ago that meant that everybody had to get COVID vaccines for everybody to be safe. Is that what you mean?
The answer is more complicated than that, as things often are in medicine. In my experience, vaccines continue to play a very important role in preventing serious illness, hospitalization and death in the face of SARS-CoV-2. This doesn't discount the validity of infection-derived immunity, but recognizes that we're looking at a coronavirus with a short incubation period and a mucosal pathway initially. Cellular immunity takes a bit of time to initiate, so circulating neutralizing antibodies, derived from recent infection and/or immunization with periodic boosting are the only way we'll see circulating IgG. That said, we already know that there are immune cells that are primary sites for SARS-CoV-2 infection (an article highlighted yesterday on interstitial macrophage infection with direct implications for cytokine storm and further lung involvement in Acute Respiratory Distress Syndrome, suggests some answers to things my colleagues and I saw early in the pandemic with implications for oxygen and mechanical ventilation therapies.
But my comment is broader. We've seen a whole host of effective vaccines developed since the introduction of variolation in the 18th century to the Western world (practiced much earlier in other areas of the Ottoman Empire and perhaps China and India). There is a surge, since the pandemic, in anti-vaccine sentiment that is showing signs of becoming an issue in vaccine-hesitant portions of US society. To date, for example, 121 cases of measles have been documented to CDC in 17 States and New York City (reported separately because of its population density). Measles, unlike COVID, has a much longer incubation time. People vaccinated for measles have time for the cellular immune system to come into play and prevent the disease from taking hold. Of note, in this outbreak, over 50% of those diagnosed with measles have been hospitalized, most because of complications of the disease but some for isolation. Complications of measles include deafness and blindness, something a number of people fail to understand and where some with strident anti-vaccine positions frankly discount. 121 reported cases, so far this year, is already more than twice the total reported cases for calendar 2023. Of course, the 2023 total pales by comparison to 2019 (in excess of 1250) and 2014 (more than 600) but we're well on our way to a significant outbreak. Long-incubation viral illness with a known and effective vaccine are amenable to prevention with adequate vaccination coverage (estimated, for measles to require 95% population penetration for those who can take the vaccine and are not excluded for medical, usually immunodeficient reasons. This an example of where population immunity can protect an at-risk population unable to be vaccinated.
Another area, and one that's unpopular, involves masking when ill, and isolation when ill. Framed on the concept of a violation of individual rights, the proper lens through which to view this, in my mind and experience, is one of self-awareness of the potential harm that can be caused to others if they were to be infected from someone who discounted the potential effect of disease. Part of the problem here is related to businesses who want their workers working and present all the time, and they view isolation for extended periods as lost revenue and productivity, rather than valuing the health of their employees. The United States made, in my mind, an estimate when we did not follow the example of Europe where business owners and proprietors were paid by their governments to keep workers on payroll and paid, so they didn't suffer during the Pandemic. We, on the other hand, recommended closing areas of congregation without consideration of what would happen to people overall, and those considered essential were expected to continue to work with little regard for protecting them from potential infection. I suspect that, had the US followed a different path we might have seen less resistance to quarantine, masking, and vaccination requirements early on.
Rehashing the COVID-19 pandemic will be the work of myriad graduate students for decades to come, and of course, there are pundits who are already doing the same. It's likely we'll learn more in the long run from the graduate students than from talking heads who didn't have to study a portion and perform a truly scholarly analysis.
And, I'd be remiss if I failed to mention the adverse effect both misinformation and disinformation had on forming opinions around both the disease, and all the varied mitigation factors. For our purposes, disinformation is the spreading of known incorrect information for malign purposes, while misinformation similarly involves spreading incorrect information and data, but we'll suggest their purposes are more to spread their legitimate beliefs, even if they're unsupported by research and evidence. There's ample evidence to suggest several state actors were involved in disinformation campaigns; we can only assume their intent was to weaken and divide our Country in the process and they likely reveled in the deepening social and political divides over the origins, process and mitigations of COVID. Misinformation likely stemmed from people who got their news and information from closed sources that mirrored their preexisting views on politics and world events, and shared what they heard widely. Of course, we had some trained scientists and physicians who engaged in one or the other, and to be honest, I'm often not sure if they were misinformed, and subsequently pedantic, or actively disinforming their followers and patients. More's the pity.
This has been a longer response than I intended but, as I mentioned, the answer isn't straightforward, especially in today's divided culture and in issues surrounding COVID-19.
Thanks for your long response, which I learned from. I got a long response myself.
In 2020 I had a case of diarrhea that lasted 2 weeks. But no respiratory symptoms. Could that have been COVID? I didn't think so for several years until I read a doctor thought it was possible.
Regarding your event where 4 out or 100 people got sick, what's the definition of a super-spreader event? How many would have to get sick to fit that definition? At an event where you spoke about intrinsic medical knowledge to what was perhaps people in the medical field, I find it really strange that people who got sick refused to get tested. It's like they did not want to know if they had COVID for some reason. Any ideas on why they did not want to know? Maybe they could not got back to work right away if they had COVID?
I sure would want to know, as treatment for COVID is far more successful if it's started immediately after infection from what I know.
You wrote: "There's ample evidence to suggest several state actors were involved in disinformation campaigns:..." I'm interested in details about that.
When I was young there was no measles vaccine. I had 2 types of measles. At that time getting the measles did not cause nearly as much concern as it does today. With poor nutrition, measles can be far more serious. My understanding is that's why measles has caused far more damage in poor nations than in rich nations like the U.S. As you may know, a few anti-vax parents actively try to get their children infected with measles. They think life long immunity is better compared to getting vaccines, and there is another benefit from infection I can't recall right now.
In 2016 about 90% of children and adolescents had gotten the measles vaccine according to the CDC. Who is getting measles this year? Is it people who got the vaccine or those that did not get it? Do we know?
You wrote: "There is a surge, since the pandemic, in anti-vaccine sentiment that is showing signs of becoming an issue in vaccine-hesitant portions of US society."
I agree. This sentiment can be blamed on the high level statements about COIVD shots and the mandates. Mandates for shots that were new and had no long term safety studies caused resentment. When the shots were new, scared people crowded around and cut in line to get COVID shots. Only a few years later the majority of people stopped doing what the CDC wants, which is to continue taking booster shots. This is partly due to COVID subsiding and the lifting of mandates. Many people now view the risk/reward a lot differently than in 2021.
For those that got the shots initially when they first became available, how many boosters would they have received by now if they had followed all the CDC guidelines?
Negative side effects from COVID shots grew into a huge number of reports. We both probably know somebody who had a negative reaction, more serious than just a sore arm for a day or 2. The government downplaying and/or doubting those with lasting negative effects and offering these people no support brought about more doubt and resentment. Judges have forced federal agencies to release data on the shots and negative side effects.
I've followed doctors who initially liked COVID shots but later changed their opinion and now say the shots are bad, based on what they've seen with negative reactions. Their changed opinions about COVID shots spurred these doctors into looking deeper into vax science and its critics, and then becoming anti-vax when they were not anti-vax previously.
We heard a lot of messaging from high level health officials and the president that turned out to be not true such as "get the shots, and you won't get COVID or spread COVID." As you know, the president got COIVD after he had his shots.
You might say that the pharma trials showed that only a few people who got the shots also got COVID, but that's not the same thing as saying "you will not get COVID." People do not like lies being told to get them to comply with policies. The shots given during the pharma trials were not exactly the same as the shots given to the public, something that if known would have caused even more doubt.
Also, high level messaging reported as factual said that if only everybody would get the shots, then COVID would go away. "We must get COVID shots to every human on earth" became a policy proposal taken as very important and reported by media. This also turned out to be false in nations where almost everybody got the shots.
People who refused the shots were demonized. The chief editorial writer of the L.A. Times wrote we should celebrate the COVID deaths of anti-vax people. Being demonized motivated a lot of people to listen more to anti-vax sources.
The governor of California wanted to force all school children to get COVID shots, but he was stopped. He now has sort of apologized for some of his COVID policies, such as shutting down the schools for so long. All these things added up and resulted in more people doubting public health and vaccines. And maybe more people joined causes to defend their right to refuse vaccines for their children and themselves.
You wrote: "Rehashing the COVID-19 pandemic will be the work of myriad graduate students for decades to come, and of course, there are pundits who are already doing the same. It's likely we'll learn more in the long run from the graduate students than from talking heads who didn't have to study a portion and perform a truly scholarly analysis."
This needs to be done now, before people forget things they said and evidence and documents might disappear. Anthony Fauci has already forgotten things he should not have forgotten, unless he's lying.
@Doug Cragoe: As for your inquiry about 2 wks of diarrhea due to COVID19, I would venture to say yes, except you did not claim to have been ill otherwise prior to those 2 wks and no mention of testing for COVID19. Diarrhea has many causes, including dietary. Nevertheless, many various signs and symptoms that aren't severe can be a result of the virus. Even more receptors such as the neurotransmitter receptors a7nAChRs and attendant mitochondria are also affected and can be of serious consequences esp when associated with the blood vessel lining called the endothelium. Endothelial a7 receptors ares said to be a critical component for myocarditis, acute coronary insufficiency, new onset arrhythmias, biliary disturbances (GB disease without stones), as well as diarrhea.
There is a nice pictorial from Nature Medicine by A. Gupta et al July 2020 1017-1032, but I can't copy and paste here.
Thanks for your reply. At the time in early 2020 I don't believe COVID tests were widely available to the public. But even if they were I may not have got one, since I had no respiratory symptoms and or any other indications of sickness. In later years I wondered if there was any available tests to see if I had COVID in 2020. Since the anti-bodies fade with time, I learned that COVID anti-body tests done long after a possible infection could not detect that infection. But then I read about a test that could, but details on that test were impossible to get, and I don't know how accurate that test might be. Do you think it's possible for me to today get a test that can tell if I had COVID in 2020?
@Doug Cragoe: A brief search with the MS copilot returned this response that puts it in perspective. I agree with it (AI searches at this day and time are generally OK but not outstanding.)
“In summary, while antibody tests can provide insights into past exposure to SARS-CoV-2, they do not definitively determine immunity or predict future protection against COVID-19. ”
Early in the pandemic, many drugstores offered antibody testing and I thought it was a scam effort by commercial labs, because it was not definitive in any way, shape or form. It gave people the false impression they didn’t have to worry if they had antibodies, but did not understand the sequence of antibody production nor the timeframe. I did not use any of those test kits, and I suspected there were disclaimers, but that was often overlooked by the anxious Consumer IMHO.
Thanks for your reply. If I ever use an AI chat bot like MS copilot. I would want to use one that simply answered the question and not go on about why it think I asked the question. And if it did not know the answer, then admit it did not know the answer. My question was is there any test that could tell me if I had COVID in 2020.
AI chatbots have been shown to give false results. And they are known to make things up that are false. It's called hallucinations. The makers of these AI chatbots don't know why they make things up that are false.
I use search engines because with them I have an idea of where the information is coming from and can make my own judgement as to the validity of the writing. I can also check other websites. I asked the question here because this substack writer has some knowledge in this area and I was seeking an informed opinion. I just did a quick search and found out these anti-body tests are not very accurate, and anti-bodies generally only last up to a year after COVID. So I will likely never know if I had COVID in 2020.
Agree with Dr. Sullivan.
I composed another long response but it seems to have been lost somewhere. I'll try to revisit your questions.
That's quite an experience in your "super-spreader" event. (no offense or pun intended). I am now a retired MD having been involved with every phase of this pandemic since early 202O. When I was working in a post-acute care unit (LTACH caring for ICU-type patients) we were asked to "please do something" by patient advocates, most being a spouse, child, sib, etc. Not many physicians. Why? Because they already did "all we can do" and dutifully prescribed all the official EUA protocols. Much to their surprise not all the victims responded the best available - dexamethasone, MCAbs, remdesivir, tociluzimab and the like. Many victims required ventilators, hi-flow O2 and sometimes dialysis when things went south. It was deemed inappropriate, in fact, job-terminating to Rx anything but official protocols whether the first round or the last round and the patients were deteriorating, nonetheless. The LTACH team got the worst of the worst cases and had no precedent therapies to offer. Yes, some of these same patients got HCQ and ivermectin, but often surreptitiously - mostly pre-hospital, and showed, not unexpectedly, zero benefit. Some were prescribed HCQ and ivermectin in later stages and coincident or not, had more complications - cardiac, renal and hepatic among them. So, in the LTACH a novel therapy was provided after consultation with families grateful for something that might help with little risk based upon decades of experience with an FDA-approved drug used world-wide and with a well-studied safety profile for victims of the disorder sickle cell disease. So what's the problem prescribing a drug restoring vital cellular dysfunctions and physiology gone amok for disorders demonstrating the same dysfunctions as progressive COVID19? Rigidity, adherence to EBM without regard to patient advocacy or a novel scenario demanding a different approach - recall the definition describing a repetitive procedure and getting the same negative results). Well, the drug is still being prescribed, mostly in the outpatient setting since the number of hospitalizations has plummeted this past 1-2 years. A diminished patient pool greatly reduces the incentives to get large studies of patients willing to participate in a funded study. Try getting funded for a study using a repurposed, generic drug even if there are NO adverse consequences for a 5 day course, no economic disincentives, and consistency for a positive outcome in hours to days, not weeks, mos, or in the case of Long Covid, years. I am not promoting misinformation. I am promoting common sense and patient advocacy. There are basic principles of scientific discovery deeply entrenched with this approach. Efforts to alert the FDA, NIH etc about the clinical outcomes have fallen on deaf ears. We are not conspiracists. We believe it is all intertwined with the politicized and misinformation campaigns by proponents of HCQ and ivermectin. Repurposing has been poisoned and there is little to no ROI potential for commercial purposes. Long preamble Dr Creager but your colleagues are part of the barriers we have encountered. Disbelief in any and all scientific approaches to prevention as well as therapy and therapeutic research has been stymied by rigid minds and adherence to EBM despite the consequences of premature death or prolongation of multisystems dysfunction. Among those consequences are post-Covid cognitive issues, cardiac arrhythmias appearing months after Covid19, myocarditis, renal disease, pulmonary fibrosis, etc. Your colleagues, like it or not, vaccinated and/or boosted, are deniers and little can be done to make them see reason as long as they have closed minds. That includes physicians and nurse practitioners, in our experience. 6 prescribers in our area can attest to helping nearly 2,500 patients to date. As you stated, Covid is still around, it's not seasonal but it continues to get a boost when people gather and are exposed to others with "cold/allergies/ tickle in the throat" issues. The issue with Paxlovid is its basic pharmacodynamic - it's an antiviral, pure and simple. As for efficacy with the newer variants, it's not at all surprising that it's not as effective for symptom control acutely or for the long term, ie LC/PASC. Our own clinical experiences and increasing knowledge about the virus' mechanisms of action is now going into its 5th year. The basic science, immunology and epidemiology has become increasingly more clear because we have approached this disorder with an open-mind and are willing to share what we have learned with like-minded (open-minded) persons. In the case of the 6 prescribers, they are unique as they are true patient advocates and not beholden to rigid protocols. Treating with a pure anti-viral in the early stage of replication is simply not enough. The virus has invaded and disseminated soon after exposure. If you test too early and it's negative, there is a false assumption that "it's not COVID19", and Paxlovid isn't appropriate according to the PI. If you wait until you are at your worst your test may again be negative. Testing for the antibody status to determine whether you did or did not have COVID19 isn't consistently helpful. If you have felt un-well for weeks to months and your IL-6 and TNF levels are elevated it supports the contention you had COVID19, but what then? There is no approved therapy at that point. Paxlovid data does support the fact that you greatly reduce your risk for being hospitalized acutely and likely won't die, but it doesn't address the risk of continuing PCC/PASC issues. Repeated COVID19 raises your risk of a PCC/PASC/LC scenario. Google or do an AI study (or 3) to read about a7 nicotinic acetylcholine receptors and COVID19, hydroxyurea as an immune modulator, and the anti-idiotypic antibody network as related to Long Covid. You will learn much. I have. It's ongoing. My biochemist/immunology colleagues have ongoing experiments clarifying the mechanisms and the targets for this disorder. Let the naysayers keep on denying. There is a pervasiveness and unwillingness to understand the how and why. Ok, I'll end my rant there. I feel for you and I appreciated hearing about your experience. It's only one of many I've heard for the past 4+ years. The controls are the colleagues with which you gather and those that chose no Rx vs some Rx. A most impressive scenario I was privvy to was the case of 5 healthy 40-70 yr old men working in a Federal capacity who gathered in a small restaurant for a long lunch, all 5 came down with the Delta-era COVID19, all were hospitalized (when hospitals were inundated with COVID19 victims), 1 (a twin 70 yr old) took 2 tabs of HU on the way to the hospital, his brother declined the HU. The other 3 declined HU and were put on vents within 36 hrs. The Rx'd twin's O2 sats in the 70's climbed to 90 within 12 hrs so he was discharged. His twin and the other 3 were dead within 10 days despite "official protocols". Coincidence? Luck? Bad karma for the dead? Do you try a little harder when the official protocol isn't helping? I sure would. I could tell you dozens of other similar stories. Again, the key to the disorder in our experiences and research is the ultimate targets and the host antibody response. You won't get better with a slug of decadron (one such Clinic locally is currently reportedly treating Hispanics by fraudulently injecting decadron @$700 as a COVID19 cure) or the infusions of remdesivir, or MCAbs, as has been shown for all but the archival strains. Paxlovid is a stop-gap with limited benefits, mild-moderate ADR's, non-durability in some cases, but a very very lucrative one at that. HU cost for 5 days? $5.90/10 tabs. It's a complicated disorder and it's ongoing. The public deserves better. Molecular screening and mining EHR's takes years and personnel. When NaCl and O2 by mask turn up as the #1 and #2 therapies for COVID19 on the CDRC/Cure ID website after screening on the massive scale, you know that a bureaucracy is in charge, but it's a fact and I/we are saddened that our ~500 case reports of a viable/credible COVID19 therapy have been totally ignored by the FDA. Close-mindedness again.
You provide a LOT to unpack here. I'm still looking at case reports and the rare published clinical trial for HU in COVID-19, and the results are "interesting". I'm having trouble envisioning the biochemical pathway to improved efficacy of HU however.
As for the use of a variety of treatments off-label, my colleagues early in the pandemic were "just doing it" if we saw something that showed promise in the torrent of literature that was coming out. Trials were not randomized but they were coordinated in-house. Management (bean-counters) were rarely involved. Our experiences with HCQ and ivermectin were uniformly, and rapidly bad, so they were abandoned early on. To the best of my knowledge, no one suggested HU in that timeframe.
@Dr Creager: I do appreciate your willingness to dialogue here or privately as you wish. Few physician/scientists seem to have any interest in a potential "sleeper" like hydroxurea (HU) since it is invariably associated with oncology and the PI lists dozens of POTENTIAL ADRs. (Read a PI for COX2's or other NSAIDs and be equally frightened I've told patients). I've yet to see ANY comments about HU's life-altering benefits for sickle cell victims or positive comments about HU safety or utility in SCD from Hematologists in any of the many interactions I've had online over the past 4+ years. Much is known about the pathophysiologies of SCD and only the casual reviewer will focus on abnormally shaped RBC's with attendant micro-vascular occlusions as the single cause of a sicklers grief from generalized pain, thromboembolisms and opioid addictions. The disorder is far more that genetic derangement of the red cell membrane. It's also a system disorder. Multisystems inflammation with associated vasoconstriction, endotheliitis, and tissue hypoxia are significant derangements in SCD crisis must be addressed. The quick and dirty fix for the suffering SCD victim in crisis is hospitalization for IV fluids, morphine, blood exchange transfusions to "dilute" the crenated/sickled cells made worse under the circumstances of the acute inflammatory processes but these modalities merely deals with the crisis temporarily. HU is the mainstay drug for the Hematologists preventive therapy (until the CRISPR gene-molecular editing is a reality for real-world cure) and HU been approved as a safe and durable therapy for decades even advocated for infants at 9 mos of age over a life-time. The literature on HU and SCD provides much basic science and provides a foundation for appreciating some of the same pathophysiologies of inflammation, vasoconstriction with the role of NO in mitigating the tissue hypoxia. I have many references on file after nearly 5 yrs of study. Then there is the new found evidence from the lab. The unique experiments designed by our collaborators defining the role of HU in relation to the viral-host ultimate targets we believe to be a key in understanding the cellular biology and immunology of the disorder COVID19 and possibly PASC. You mentioned difficulties finding articles about HU and COVID19. It's helpful to "buy into" the concept that COVID19 is indeed an immune disorder precipitated by the SARS-Cov2 viral-host interaction and the targets are critical molecular structures right from the first exposure by a susceptible host (includes vaccinated and unvaccinated). Perhaps you located the PISCO trial on ClinicalTrials.gov. It was a Mexican trial relating pyridostigmine for treating COVID19 and was addressing the a7nAChRs but never was completed for unknown reasons but I suspect it related to funding or expertise for analyzing the outcomes since there was no f/u data was never ever submitted to the ClinicalTrials. My attempts to contact the corresponding author were futile. Otherwise, I am not aware of a single published human trial with HU or pyridostigmine. We contend that HU as an immune modulator must initiate any therapy addressing the immune-disabled targets, the a7Rs, prior to treating the neuromuscular pathophysiologies in severe/advance COVID19. That was our experience and we published case reports describing that rationale. At the time we only had a few dozen patients but as time passed many more were treated both inpatient and outpatients having no precedent therapies to offer COVID19 victims. I am gratified to know that others had similar misgivings (and a horror) for doing nothing and recognizing the futility of the HCQ/ivermectin claims. Perhaps your alternatives were being used before the availability of the EUA protocols or possibly after the EUA protocols failed? Or were alternatives used in conjunction with the EUA protocols. Perhaps your hospital leadership recognized that as physicians you and your colleagues were using intellect, expertise and advocacy for trying alternatives. Did you get any negative feedback or outright threats for using "unapproved COVID19" therapies? I can tell you many horror stories from our experiences. HU was the 1st and only plausible drug that popped up into our collective consciousness - the medical LTACH team. The lead hospitalist had hematology experience, a working knowledge of basic cell biology and physiology/immunology and was familiar with SCD crisis management. The principle derangement that was being addressed is tissue hypoxia. In the case of progressive COVID19 as well as sickle crisis, it's multisystems inflammation, etc. The first LTACH patient responded promptly to the HU. Subsequently pyridostigmine was added to a vent-dependent COVID19 victim (long since PCR negative upon admission to the LTACH) since it was an antidote for reversing the toxic effects of vercuronium, the paralytic necessitated for the patients repeatedly "un-weanable" vent tethering in the acute ICU before his "last ditch" referral. Subsequent to a brief course of HU, NG-oral Mestinon was cautiously titrated up and the patient "rose from the dead".
For 3+ years we have collaborated with a team of Biochemists, Physiologists, Immunologist who have published for decades and their knowledge base for a7Rs seems unlimited. This basic cell biology expertise with the a7Rs was the reason I made contact and introduced the concepts for our clinical therapy with HU in COVID19.
Here is the definitive article:
Ref: https://www.jni-journal.com/article/S0165-5728(23)00230-8/fulltext
Journal of Neuroimmunology "Hydroxyurea interaction with a7 nicotinic acetylcholine receptor can underlie its therapeutic efficacy upon COVID19"
The key concepts derived from these unique experiments is summarized:
HU interacts with a7nAChR resulting in anti-inflammatory and pro-survival effect.
HU treatment prevents a7nAChR-ACE2 interaction in the brain of mice
HU treatment stimulates IgM to IgG class switch in mice immunized with SARS (674- 685 spike protein fragment)
HU affects immunoglobulin glycosylation resulting in anti-inflammatory phenotype
HU treatment prevents memory impairment in mice immunized with SARS (674-685)
Ref: https://www.jni-journal.com/article/S0165-5728(23)00230-8/fulltext
Further information about COVID-19, a7Rs and PASC:
Ref: https://doi.org/10.1016/j.biocel.2024.106519
Case Reports from our very early experiences (lead author is not a Clinician)
Ref: https://doi.org/10.2478/jccm-2021-0019
Ref: https://www.aimspress.com/article/doi/10.3934/medsci.2023010
Ray Sullivan, MD
sullray<at>gmail
I'll be following up. I've been busy of late (will explain in email, you will chuckle). And thanks for the references. I'll start looking at the ones I've not already found.
The group I fell into recognized early on that SARS-CoV-2 was not creating a "normal" ARDS/pneumonia, and started trying other tricks. We'd tried steroids at various dosages, as did other groups, but too early in the course of the disease, and often as a last-ditch measure. And we went away from steroids. Imagine our dismay when dexamethasone in week 2 of the course of illness was found to be effective... and at nearly trivially low doses. We tried the antivirals, and even some anti-retrovirals. To no avail, although there's new research suggesting some of the anti-retrovirals may hold some hope for treating Long-COVID based on a couple of preliminary reports. Mostly, we ended up focusing on delaying intubation and controlled mandatory ventilation for as long as possible, preferring, instead, the non-invasive approaches. Our mortality improved enough to move the needle but early cases, and case fatality rates, were grim regardless. Exposing an immune-naive population to a novel viral agent with a high affinity for human cells had significant consequences.
Our group was one of the first to recognize SARS-CoV-2 as a vascular disease, but it took us a bit longer to recognize this was likely an immune response. This was because autopsy analysis actually found evidence of replicable virus in atheromas, suggesting either an affinity for cholesterol-rich environs, or were clustering in damaged microvascular sites and attracting fatty depositions. We suspected damaged vasculature might have more cells with ACE2 receptors due to the damage but never went beyond hypothesis. In retrospect, an immune-mediated response in the microvascular space makes more sense, but still fails to explain the collections of replicable virus.
One benefit we had was that there was never mention on our chats of hospital leadership getting overly involved. In all three institutions, the clinicians had pretty free reign, limited mostly by what the pharmacy could provide: It was hard to get additional supplies by then if we came up with something really hare-brained. Of course, I was not clinically involved, but no one ever said, "Administration told me no". I should follow up with the folks from the past and see if that became an issue later, or if they were simply left alone.
I'll follow up with email.
Our paper describing molecular biological mechanisms for repurposing hydroxyUREA as a credible therapy for COVID19 was just published for all to see. It is our fondest hope that it will alert appropriate clinical research entities (preferably un-affiliated or beholden to big Pharmas) to delve into these heretofore un-described concepts linking the a7nAChRs as the targets for the viral-host-immune response and the role of HU as the preferred therapy as an allosteric immune modulator described exquisitely by Ben Mofftah & Eswayeh pharmacologists as well as the team of Biochemists with whom we have collaborated for over 3 yrs. Our consistently positive clinical experiences using HU as a novel repurposed therapy for severe COVID19 victims have been translated into a unique series of experiments leading to this and other original discoveries about SARS-Cov2 and host mechanisms. As for mortality during the peak of the pandemic without HU it was significant (~25%) but even 2 doses of HU appeared clinically to interfere with the virus' invasiveness, dissemination, endotheliitis, hypercoagulation, and progression to ARDS scenario. Controls were groups that had a common source and declined any therapy (none available until Paxlovid arrived anyway) and active therapy with the HU protocol. NONE that took HU progressed while many (can't give a figure) that declined HU were hospitalized and some of them died within 10-14 days. The rural city of Thomasville NC was especially hit hard as many died of COVID19 and related disorders. Case Reports numbering nearly 500 entered into the CDRC/CURE ID system provided some documentation for the oversight management of the FDA, that chose to ignore any and all of these consistently positive clinical outcomes after taking HU. Aside from HCQ and ivermectin, few other credible RCTs were supported by any clinical research entities and none showed convincingly positive outcomes, aside from Pfizer's pure antiviral Paxlovid.
Ref: https://doi.org/10.1016/j.bbrc.2024.149825
Ref: https://doi.org/10.1016/j.biocel.2024.106519
Ref: Ben Moftah M, Eswayah A. Repurposing of Hydroxyurea Against COVID-19: A Promising Immunomodulatory Role. Assay Drug Dev Technol. 2022 Jan;20(1):55-62. doi: 10.1089/adt.2021.090. Epub 2022 Jan 6. PMID: 34990284
Found that and read the paper. Interesting. Makes this worth looking into more.
No question or random neural firing is off-limits. 😉
As for inquiries about lab techniques, reactants, lab equipment I would have to plead je ne sais being only the pure clinician with medical science gleaned over many years of patient experiences and 5 yrs delving into COVID19 related research topics.
Thanks for your candid remarks. I look forward to further discussion. Our experiences with administration and unit leadership in our host hospital was nothing short of abysmal. Despite a high ICU mortality in the 25% range, the official protocols remained the only game in town in the acute setting. Our lead Hospitalist worked in both the acute ICU as well as the LTACH being officially employed by an ourside Hospitalist group. He saw first hand the failures in the acute setting and even when the early successes from the LTACH experiences were evident, there was no effort to examine those successes or change the EUA (heavily subsidized, I would venture to add….) protocols. The threats to his job security were not subtle at all. Do as we tell you, in essence. Kudos to your administrations and pharmacy for supporting your efforts even if they were not as successful as ours. I view the successful outcomes with the introduction of the Decadron as somewhat serendipitous in the sense that studies showed benefit at that stage of cytokine activity driving the O2 demand higher and higher and mechanical ventilation a necessity over Hi-flow or BiPap O2 support. The cytokine response for most critically ill patients was such a red flag that it’s difficult for me to envision not using a steroid in that setting. Given the utility for reducing brain edema after brain surgery, it made sense to use decadron over hydrocortisone as I view the scenario. I was not clinically active during this pandemic. I am simply being the arm-chair QB and using that ol’ retrospectroscope. My role was to assess the proposed novel therapy by our clinical team fbo post-acute advanced COVID19 victims and provide input as to the credibility for using HU in this setting without the benefit of those EBM and highly powered RCT’s in such an emergent scenario. It made sense to the entire team as well as 2 consultants such that they have continued to support the role of HU based on their own personal and professional experiences with the drug - even after 5 yrs of clinical use. They made the effort to review those novel experiments devised by our International Biochemistry/Immunology collaborators under our clinical directions demonstrating the how and why of our consistently positive outcomes. We have yet to convince any entity to repeat the published experiments or contemplate trials. The window of opportunity for these trials has closed, I fear. Fewer advanced COVID19 patients and more infected people choosing to “take their chances” that the “cold symptoms” aren't so bad and the mindset that only those with advanced age or co-morbidities will suffer with PASC consequences. Paxlovid has its limitations as a pure antiviral in our view.
There were some institutions where heavy handed administrations took hold. I was not personally involved clinically, but was invited to join a gaggle of clinicians from at least 3 major institutions mostly in the West. I suspect their various administrators didn't meddle much in the early days because they were too scared to show up on the wards and in the ICUs, but I heard no suggestion that anyone was meddling.
Our discussions of steroids early were meant to try to stave off the cytokine storm we were seeing in patients. And early, we saw this in the first few days of hospitalization, but in retrospect, that was likely 7-10 days into the illness because people were presenting so late, and were so debilitated that high-dose steroids didn't help; in those who were not that far along, steroids likely muted their initial immune response, reducing available humeral antibody production and reducing their chance of dispelling the virus. In other words, while timing was everything, we had no really good handle on the timing to administer steroids, even though it seemed obvious that was going to somehow be useful. Our teams adopted decadron hesitantly because we'd already tried steroids and our results were mixed... at best. But once our clinicians understood the timing requirements, we embraced it.
Your results with HU are interesting. I want to offer that the reticence to look at your results could well have been colored by the scandal engendered by Didier Raoult and his claims of broad success with hydroxychloroquine that were not reproduced in any subsequent study, including several that are still theoretically underway. His claims poisoned the well for a lot who might have otherwise revisited the repurposed drug arena. I'm not sure what he hoped to accomplish but several large-scale studies attempted to reproduce his results and were terminated for futility and increased mortality. That was unfortunate.
I agree that we're likely to see fewer advanced COVID-19 patients in, at least, the near term, but I remain concerned that we're no more than one significant 40-base variant away from another significant peak. On the positive side, enough people have been infected to date, with or without the vaccine, that they likely have trained up the cellular system to recognize S1, as well as nucleocapsid antigens, so the cellular response will be stronger. This doesn't preclude significant cases in immunocompromised individuals, nor in those who are infected with an extreme viral load, but hopefully we will be spared the difficulties of 2020 and into 2021. As you note, too many are discounting the virus' capabilities as a multi-system agent. Our little discussion group began referring to SARS-CoV-2 as a vascular actor by no later than July once we started understanding the impact on lung tissue... and the fact that we were not dealing with the same acute respiratory distress syndrome we were used to. We saw more barotrauma in unaffected lung, found that we were less able to recruit affected alveoli with PEEP/CPAP, and that residual alveolar fluid seen at necropsy was closer to a gel than a liquid (one pathologist described it as an aerogel rather than a liquid). Vascular changes in the alveolar capillary bed were also seen, contributing to microclotting, and this correlated to microclots in solid organs and distal vasculature. What was curious from that was that we saw few real pulmonary embolic phenomena, but that strongly suggests this was acting more on the arterial side than venous. I never fully sorted that out in my mind. That will remain a topic for graduate students and MD/PhD students for a generation.
The American public has gotten over this virus, but doesn't seem to understand that the virus is still around and still looking for ways to reproduce. Until it settles into a ladder-like mutation scheme, the random mutation pathways will render us vulnerable. A lot of effort has to go into PASC, and we need to restore faith in the Public Health community, as that group (and I tend to drop myself in there) did a pretty good job of meeting and understanding the virus and pandemic, but we failed in our attempts, for the most part, to communicate what we knew to the public, and even when we had sufficient time to talk to decision makers and answer their questions. they often went looking for another position or opinion that better fit their preconceived notions. Too often, they found those in social media or "news sources" that were not playing with all the info, or worse, were manufacturing information for the purposes of explaining things as they best understood them (without the benefit of clinical and educational experience), or worse, with an intent to mislead. I saw this too many times.
As for PASC, in our concepts and the research of Dr. Maryna Skok, the basis is the immune response to the virus gone amok and it's a consequence of the anti-idiotypic antibody network - the antibodies to antibodies. Therapy should begin with an immune modulator, specifically, HU that restores the function of the a7Rs. My colleague has some early limited therapy experience with a brief HU course followed by a low dose titration of the more centrally acting enzyme inhibitor Exelon approved for AD having much the same pathophysiologies involving the a7Rs. You might say that AD is the proxy disorder for Long Covid brain fog as we envision the multisystemic pathophysiologies of Sickle Cell crises the proxy for COVID19. They both respond to the ACh enzyme inhibitor.
Dr. Skok's paper on a7Rs and PASC:
Skok M. The role of α7 nicotinic acetylcholine receptors in post-acute sequelae of covid-19. Int J Biochem Cell Biol. 2024 Jan 11;168:106519
With regard to our clinical approach treating Covid , we were dealing with post-acute ICU patients that were aggressively managed with the usual approach for any progressive respiratory failure. Like The clinicians in your arena, steroids were used Liberally and much like a shotgun approach. As you described, often it was too little too late or too much too soon. Steroids were parsed for individual scenarios. Various intravenous, antivirals and immune globulins were used as well as diuretics, and often antibacterials were added. It was all hit and miss. As The EUA protocols appeared things didn’t change a whole lot But there were suspicions that drugs like remdesivir were adding insult to injury, especially in the cardiac and renal areas. Many of the physicians started getting used to the increased mortality. Burned out with all the death and dying, and a sense of futility or what they were doing, but they wouldn’t admit it and administrations wouldn’t let them try other things. Those patients that had more aggressive family/advocates and physicians that heard about our successes, began the referral process in that early stage of 2020. In the post- acute LTACH setting, there were no precedents for therapy of COVID-19 so we had to dig deeper. Our lead hospitalist focused on the fact that some patients came in with low oxygen saturations, but a relatively Mild ARDS picture, coupled with declining respiratory parameters. Also there was evidence suggestive of significant respiratory muscle fatigue. Tissue hypoxia was quickly adopted as a Target and with his experience taking care of sickle cell patients, being from the eastern Mediterranean area, he raised the issue of using hydroxyurea a mainstay for SCD. We immediately did some in-depth reviewing of The pharmacology and physiology having been well-studied with sickle cell disease. Hydroxyurea met all the criteria, and it was decided that a trial course of five days would be reasonable and safe. Many of the patients came in with elevated white counts as one would expect with a viral or bacterial pneumonitis so a slight diminished white count after 3 to 4 days was not deemed worrisome, but a reasonable response. Well, it wasn’t just the white count that diminished, so did the oxygen demand, the respiratory settings declined, respiratory effort was improved, and the patient’s entire picture changed in just a matter of 2 to 3 days. We knew we were on to something. One particular patient came in with a particularly bad picture and weaning was a real challenge, even after a few days of hydroxyurea. It turns out he probably was a slow metabolizer of vercuronium , A curare like paralytic enabling him to stay on the ventilator without violent resistance. He had failed multiple weaning attempts in the acute ICU, and we were charged with trying to wean him, given our good experience in that realm over several years. The antidote for the vercuronium toxicity was pyridostigmine. Within hours his scenario showed dramatic improvement starting with eyelids, ocular motions, improved swallowing, cognition, respiratory efforts, etc. The AChEI was titrated up and then down until he was able to be extubated and his clinical picture became so much improved. Thereafter it was felt that a cautious trial of the same AChEI might benefit other post acute Covid patients, and indeed the rehabilitative efforts were greatly shortened. Patients with multiple chest tubes to drain effusions, residual fevers, renal dysfunctions, cardiac arrhythmias, all showed striking improvement with a short three day course of the HU followed by titration of the ACHEI. During that time, I was doing the research on the a7 receptors and found the expertise in an unlikely place, Kyiv, under siege by the Russians. One of the biochemists also a molecular biologist, immunologist responded to my inquiries and we developed a collaborative relationship thereafter. She is the corresponding author on that recent paper on several papers as I noted on other comments. Additional studies have been performed and are in publications. She had planned additional collaborations with German electrophysiologists with whom she had worked in the past. Sadly, on April 11, she had a sudden death, possibly “a clot or MI” and I have yet to hear what will become of our momentum. We are all at a loss at this stage. Large scale studies and comparison trial are needed but with the significant decreases in hospitalizations and acute infections the window for that may have closed (temporarily). Anecdotally (on top of anecdotes!) my Hospitalist colleague has continued to treat outpatients who have heard of him word of mouth or were treated 1 or more times in the past with other variants. He also believes that Flu A & B respond to his HU protocol since many signs and symptoms point to the same a7Rs as targets so this type of PAM2 allosteric modulator HU is effective for those viruses as well. “They do very well with 5 days of HU” he declares.
My suggestion: do what the HCQ/Ivermectin doctors did. Create your own website about HU treatment for COVID. Include your dosage level, when to use it, what drugs or treatments work well in combination, scientific studies, how to contact you for questions. Don't try to go through the system anymore, go around it. You might increase knowledge of your treatment and more doctors using it. You might use it to raise money.
You wrote:
"Repurposing has been poisoned and there is little to no ROI potential for commercial purposes." I think repurposing was poisoned long before COVID. Big Pharma has an outsized influence on top medical journals and federal regulatory agencies. Eliminating the competition is good for business. Pharma is the biggest spending lobbyist category in DC by far and has a revolving door for high level regulatory officials that retire and then go to high level executive position at Pharma companies, and vice versa.
Funny how your complaints about the medical system are very similar to those that came from the HCQ/Ivermectin doctors. Example from your post: "It was deemed inappropriate, in fact, job-terminating to Rx anything but official protocols whether the first round or the last round and the patients were deteriorating, nonetheless." This happened to HCQ/Ivermectin doctors who were fired and lost academic careers. One of the top advocates for Ivermectin was out front in 2020, advocating for the use of corticosteroids for COVID treatment. The entire world medical system including the WHO was against it, and said he was wrong. But within a year a corticosteroid -dexamethasone - became widely adopted and standard practice.
@Doug Cragoe: Another point about my own website relates to some of the folks that tout HCQ/Ivermectin. I do not want to get lumped into that sort of hype. The most egregious example is a physician named Kory. Surely you've heard of him. Touting ivermectin for prevention, active infection, lingering infection and when all that proved to be bogus, he went after the vaccine ADRs and characterized the ivermectin almost as an antidote "for those horrible shots". His website gives you more insight into the motives. For a mere $350 he will consult with you and give you an RX for his wonder drug. Discounted if you speak with his NP. I've heard that he also took it as a weekly preventive and got a bad case of COVID. He recovered and I have a pretty good idea what he was given and it wasn't ivermectin or HCQ . No, I want to have a credible presence and a clinical confirmation from researchers that buy into our 5 yrs of research and sound pharmacology principles. The numbers of infected people are lower and fewer are hospitalized currently , but I do think this coming Fall we will see another variant and those number won't remain low. Recipients of HU have all been pleased with the rapidity of response, the durability, absence of side effects and low cost.