The linked case report (I'm always concerned about things disappearing). Dr. Scheim, where did the case report come from?

Patient is a 65-year old female living in Atlanta, GA, USA, weight 130 lbs.

Her symptoms began with a dry cough late at night on Tuesday, April 21. The dry cough continued on April 22. The next day, April 23, she “felt awful. head like twice its size, body felt heavy all over, very tired.”

The patient had been practicing social isolation, staying mostly at home, using a mask going shopping, but had stopping briefly at a young friend and greeted her without a mask, someone who turned out to have a family member with COVID-19. COVID-19 at the time was prevalent in her area, and there is little possibility that she caught some other type of serious disease. The symptoms as they developed, in particular rapid deterioration of breathing function on May 6-7 were classic for COVID-19. However, both an antibody test and viral test taken on May 1 came back with negative results; the track record of accuracy for test kits being used in Georgia is not clear.

Cautionary tale: keep the damn mask on, even with friends.

She stayed at home throughout the course of her illness, with her treatments confined to oral medications. On Thursday, April 23, she took 18.2 mg of ivermectin. The next day, April 24, she took 13.6 mg. Over those two days, that was a total of 31.8 mg, for a total dose of 538 µg/kg. She also took chloroquine intermittently from April 23 thru May 4 at a cumulative total dose of 5,650 mg.

On whose advice? An MD's, apparently, since she would need a prescription for both drugs -- assuming she doesn't work in a pharmacy.

On Saturday, April 25, she felt as if she were totally well. She began taking doxycycline at 200 mg per day on that day, which she continued at that dose through May 7.

Again, where is the MD getting his/her treatment ideas? This is before the initial Bangladesh story with 60/60 patients "cured" by ivermectin + doxycycline.

Uh, google informs me that there was considerable interest in doxycycline before the Bangladesh report -- which is probably why they used doxycycline in Bangladesh (also because it's cheap and available in that country).

The patient continued to have assorted minor symptoms through May 5. These included sore throat, headache and tiredness. On Wednesday, May 6, she became out of breath just walking around the house. This shortness of breath escalated until on Thursday, May 7, she sat down and had trouble breathing for five hours, around noon to 5 PM. At about 3 PM, she then took another dose of 18.2 mg of ivermectin. On Friday, May 8, she took an additional 9.1 mg of ivermectin, for a total dose, May 7-8, of 27.3 mg (total 461 µg/kg). Also, on May 8, she took 100 mg of doxycycline in the morning, then 250 mg of azithromycin; she continued azithromycin at 250 mg per day afterwards, through May 12.

Whoever she was, she apparently took excellent notes!

The fact that her symptoms got worse 12 or so days after she stopped dosing with ivermectin implies that ivermectin's effect does not persist, or it just doesn't work?

Difficulty in breathing subsided later in the day on Thursday, May 7, and she had no breathing difficulty afterwards. On Friday, May 8, she took a .3 mile walk and was out of breath afterwards. On Saturday, May 9, she went out on some short errands with a mask and took two walks of .4 miles each, just slightly out of breath afterwards. On Sunday, May 10, she received an oximeter and began using it; her oxygen saturation was 98%, and subsequent readings were in the range of 96-100%. She continued to take walks three times a day beginning that Sunday, slightly out of breath after the first walk on Sunday, but not since. She has felt normal and free of all symptoms since Monday, May 11.

Or it does.

She took ivermectin on 4/23 and 4/24, and felt "cured" on 4/25. Then she became ill with shortness of breath on 5/6. She took ivermectin again on 5/7 and her shortness of breath stopped, but she was winded after a .3 mile walk. She took ivermectin again on 5/8. The next day she could walk further with less difficulty breathing. On May 10 her newly-acquired oximeter showed excellent 02 saturation. She was symtom-free on 5/11.

Sounds like ivermectin did work for her.

Of course, it could have been the chloroquine, but that's less likely since her last dose was on 5/4 -- two days before her illness rebounded. Uh, did it rebound because she stopped taking the chloroquine?

Was it the doxycycline, which she took daily from 4/25 to 5/7? Apparently she didn't think so, since she stopped taking it the day before she resumed taking ivermectin. No, not the doxy.

Azithromycin? She took it from 5/8 through 5/12 -- overlapping with her resumed ivermectin dosing on 5/7 and 5/8. From the data, AZT could have been the magic pill, with ivermectin playing no role.

So this is good evidence of ivermectin's efficacy, but it's ambiguous. It's also just one person.

Edit: The disappearance of the shortness of breath after the second round of ivermectin is consistent with Dr. Scheim's suggestion that ivermectin reduces blood clotting.

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Dr. Scheim, would you please explain hemagglutination (the clumping together of red blood cells) and ivermectin? I'm unaware of ivermectin preventing clumping -- but I don't know much. Thanks in advance!

Never mind, you explain in the PDF. Fascinating idea! Sounds totally plausible to me.

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The preprint's full text (preprints go away, e.g. the Surgisphere ivermectin article that was posted to SSRN). This is just the abstract on SSRN; there's a PDF accessible from the SSRN page (where the preprint appears).

Two important take-aways:

• Ivermectin could reduce/prevent the blood clotting that is such a deadly hazard to those with severe covid-19 disease.

• From the PDF, "It would thus be possible to use a higher dose regimen of IVM for COVID-19, for example, 500 µg/kg and then 250 µg/kg every three days following."

Dr. Scheim makes both points in his post, but doesn't explain the basis for his blood-clotting theory. That's in the PDF.

Dr. Scheim's case study supports the higher dosing.

#Ivermectin for COVID-19 Treatment: Clinical Response at Quasi-Threshold Doses Via Hypothesized Alleviation of CD147-Mediated Vascular Occlusion

Posted: 1 Jul 2020 David Scheim US Public Health Service

Date Written: June 26, 2020

#Abstract The worldwide spread of the COVID-19 pandemic has prompted clinical testing of existing drugs with indicated activity against the SARS-CoV-2 virus. Among antimalarial drugs of such potential is ivermectin (IVM), a macrocyclic lactone of Nobel Prize-winning distinction. A retrospective study of 173 COVID-19 patients treated with IVM in four Florida hospitals at a dose of 200 µg/kg yielded a 40% reduction in mortality compared with 107 controls (15.0% vs. 25.2%, p=0.03). Mortality was cut by 52% with IVM for patients having severe pulmonary disease (38.8% vs. 80.7%, p=0.001). Stabilization and then improvement over 1-2 days frequently occurred for patients who had rapidly deteriorating oxygen status.

Is the breathing difficulty due to blood clumping?

The fact that ICON showed a larger reduction in fatalities among patients on ventilators supports this theory -- right?

It is proposed that higher doses of IVM could yield sharply greater clinical benefits. In several clinical studies, IVM at doses of up to 2,000 µg/kg, ten times that used in the Florida study, were well tolerated. The potential for major dose-response gains is evaluated based upon studies indicating that IVM shields SARS-CoV-2 spike protein and that this spike protein binds to the CD147 transmembrane receptor as well as to ACE2. The abundant distribution of CD147 on red blood cells (RBCs) suggests a hypothesized “catch” and “clump” framework whereby virally-mediated bindings of RBCs to other RBCs, platelets, white blood cells and capillary walls impede blood flow, which in turn may underlie key morbidities of COVID-19.

Several studies? Look at the PDF for citations; I'm only away of the one safety study Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects, which found that 2000mcg/kg did not produce Central Nervous System problems.

The proposed catch and clump scenario for COVID-19 has a parallel in malaria, for which CD147 is central to the infectious process. The core morbidity of severe malaria is caused by similar clumps and adhesions to endothelium centering around infected RBCs. These underlie the much greater incidence of severe malaria for blood groups A or B vs. O, caused by adhesive RBC membrane trisaccharides associated with blood groups A and B. COVID-19 is likewise much more prevalent for blood groups A or B vs. O. More generally, hemagglutination, the formation of such RBC-pathogen clusters, is common for enveloped viruses. Under this hypothesized framework, a significantly higher rate of capillary flow in younger people could explain a corresponding decreased severity of COIVD-19. This proposed hypothesis and the associated potential for major IVM dose-response gains could be tested, for example, by monitoring blood flow in COVID-19 patients before and after IVM intake using nailfold capillaroscopy.

This is the first explanation I have heard of (but I haven't been looking) for the observed hazard of blood types A and B with covid19 (I'm type A dammit).

#Note: Funding: This research received no external funding.

Conflict of Interest: The author declares no conflict of interest.

Keywords: SARS-CoV-2, COVID-19, ivermectin, CD147, basigin, BSG, EMMPRIN, red blood cell, RBC, erythrocyte, hemagglutination, spike glycoprotein, ACE2, hydroxychloroquine, chloroquine, azithromycin, doxycycline

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I posted this to Dr. Rajter (Broward County ICON author) on Facebook:

This is a new preprint that begins with the results of the ICON study. I am very interested in your comments, esp. around blood clotting, which isn't mentioned in your report. It would be great if you could comment on the reddit post; you'll have to sign up but that's painless, no email required.

https://www.reddit.com/r/ivermectin/comments/hjxchk/new_preprint_dramatically_better_response_for_ivm/

Or comment here, and I'll move your comments to reddit, if that's OK with you (tell me!).

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/u/strongerthrulife posted this preprint to /r/covid19 (thanks, STL!). Someone there misconstrued the article as a safety study (which it's not).

Here is my long response to that post, which musters some evidence that ivermectin is useful for severely-ill covid19 patients, among other things.

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I feel they are going way overboard with mega doses like that

they do it do extend the half-life so the drug sticks around over days, that's idiotic, just do 200mcg/kg for a few days, maybe a week

wtf do they resist doing multiple days, the virus needs to be constantly attacked as it tries to replicate, a "one shot" dose is not the right approach

I tried 600mcg/kg for the second round of ivermection (out of three) and I had severe visual problems, the smallest amount of light would cause massive strobbing in my head even with my eyes closed, I could see patterns of light everywhere, it took like 48 hours to stop happening which makes sense as the half-life would take that long to fade

it took three rounds to kill the virus enough for my body's own immune system to finally finish the task, to me that is a clear indication it takes TIME not mega-doses to persistently work

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Some notes from the PDF:

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The content of my long post about this study to /r/covid19:

Uh, no, not a safety study. It mentions that a study found that 2000mcg/kg is safe. This is the study, which was discussed in this sub here.

The author Dr. Scheim posted his preprint to the /r/ivermectin sub here. With his post, he says:

IVM at a low dose of 200 µg/kg is sufficient to begin to reverse key morbidities of COVID-19 for three or four days. But IVM at, for example, 500 µg/kg and then repeated at 250 µg/kg every three days (with azithromycin for 10 days) could be sufficient to competitively block viral bindings both to CD147 and ACE2 receptors, reversing morbidities of COVID-19 and also stopping viral replication.

He also says this in the PDF accessible from the preprint page.

He is suggesting a trial applying the higher doses.

This is probably a sound suggestion, but AFAIK Dr. Scheim doesn't have a basis for asserting it other than being a smart guy. The "every three or four days" is logical, since ivermectin has a half-life of 18 hours. Ivermectin is ridiculously safe, so there's little risk in trying it, IMO.

An Italian trial is testing higher doses, 1200mcg/kg for 5 consecutive days.

To me, the important take-away from Dr. Scheim's article (esp. the PDF) is that ivermectin could reduce/prevent the blood clotting that is such a deadly hazard to those with severe covid-19 disease. His assertion is based on a malaria model.

Ivermectin as anti-coagulant is new, AFAIK.

There are a number of news stories and reports that support the idea that ivermectin is helpful for severely-ill patients, who encounter the blood-clotting problem.

• The ICON study that /u/strongthrulife included in his post found that ivermectin reduced fatalities 52% for patients who were so sick they needed ventilators.

• Sermo surveys about 4600 doctors weekly to find out what covid-19 therapies they are using and how effective the MDs think they are. This excellent chart from @jjchamie on twitter shows that 70 or so doctors in their survey were using ivermectin during the last week of April and throughout May. 57% of them said that in the ICU ivermectin was extremely or very effective; another 36% said that it was moderately effective.

• Several protocols being applied in Latin America call for heavier doses as patients get sicker. Here is an example posted by a Peru MD.

However, no one has suggested why ivermectin works with severely-ill patients -- aside from suggestions (IIRC) that it can help calm the cytokine storm. I don't know if that's true.

The idea that ivermectin may prevent blood-clotting by binding to the CD147 receptor is NEW.

I contacted the main MD who did the ICON research to ask if he had observed anything about blood-clotting as he was treating patients with ivermectin. No reply so far.

If you're interesting in his reasoning about the possible blood-clotting benefit of ivermectin, look at the PDF.

Edit: In his post to /r/ivermectin, Dr. Scheim does offer a case report as evidence that heavy dosing of ivermectin is safe. Here is my recap of the case report:

She took ivermectin on 4/23 and 4/24, and felt "cured" on 4/25. Then she became ill with shortness of breath on 5/6. She took ivermectin again on 5/7 and her shortness of breath stopped, but she was winded after a .3 mile walk. She took ivermectin again on 5/8. The next day she could walk further with less difficulty breathing. On May 10 her newly-acquired oximeter showed excellent 02 saturation. She was symtom-free on 5/11.

The doses she took were quite a bit higher than the usual 200mcg/kg: 538 mcg/kg in total over two days, the first time she took ivermectin, and 461 µg/kg over two days, the second time.

Go to the post to see the caveats, esp. the patient was taking other drugs that might have contributed to her "cure".

Edit: In the abstract that /u/strongerthrulife posted, Dr. Scheim wrote:

These underlie the much greater incidence of severe malaria for blood groups A or B vs. O, caused by adhesive RBC membrane trisaccharides associated with blood groups A and B. COVID-19 is likewise much more prevalent for blood groups A or B vs. O.

Here is a study supporting the last sentence.

I'm blood type A so it caught my attention when the study was posted to /r/covid19 a couple months ago.

This is the first explanation I've heard of, for why blood type matters -- because until just now, I overlooked this study posted to this sub a couple months ago, that suggests a genetic basis for the blood type effect. The genetics = blood type study doesn't mention the trisaccharides that Dr. Scheim wrote about.

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