TrumpLyftAlles | 10 points
Antiviral Effect of High-Dose Ivermectin in Adults with COVID-19: A Pilot Randomised, Controlled, Open Label, Multicentre Trial (Argentina 2020-11-11) Result: Higher IVM plasma => lower viral load[-] TrumpLyftAlles | 2 points
@AOlavarria (on twitter) offers this:
It is a study carried out in healthy patients and the immunosuppressed were excluded. That is, the immune system was "like clockwork." For this reason, the IVM and control groups fall in viral load in the same way, except for those with a high concentration in plasma, where it falls faster.
[-] TrumpLyftAlles | 2 points
On 2020-09-23 @AOlavarria posted this 25-minute video about his research (Spanish with English subtitles) featuring the lead author Alejandro Krolewiecki.
He also posted this article, which has been posted to the sub, with the finding:
The study evaluating the effect of ivermectin on the replication of SARS-CoV-2 in patients with COVID-19 found that the administration of ivermectin at a dose of 0.6 milligrams per kilogram of weight (three times the usual amount) produces the faster and deeper shedding of the virus when treatment is started early in the infection (up to 5 days from the onset of symptoms).
That's not in the abstract.
[-] David_1226_ | 2 points
Note that the severity and mortality of a COVID-19 infection can be radically reduced by IVM without necessarily lowering the viral load. SARS-CoV-2 is much more virulent than the closely related betacoronavirus common cold strains, yet viral loads may be the same. A key difference is that SARS-CoV-2 promotes hemagglutination, which accounts for COVID-19 morbidities, both pulmonary and systemic. Six independent studies identify that the biological mechanism of IVM is blocking viral spike protein bindings to cellular receptors. This may apply more to SA than ACE2 receptors, in which case virus will multiply but won't attach to blood cells, won't clog up pulmonary capillaries, and will progress harmlessly in the body, even if viral loads are the same. We can't be sure that binding to viral spike protein is the actual mechanism of IVM, but six different studies point to this, and I haven't seen any other credible study or body of studies that actually apply to SARS-CoV-2, an RNA virus, at physiological concentrations. (see my paper at http://ssrn.com/abstract=3706347 )
This study is noteworthy in finding that there were no significant adverse consequences to a 3 mg/kg dose administered over a 5-day period. It would of course have been helpful to follow outcomes other than change in viral load over 5 days.
[-] David_1226_ | 2 points
In addition to my comments below, one point of interest as reported by various researchers is that viral load as measured by different PCR testing techniques can pick up viral fragments and read these as positive even without live, intact virus. These results are in conflict with others showing a sharp reductions in viral loads within days of IVM administration. Still, as I wrote in my prior comment, IVM could radically reduce severity of COVID-19 without reducing viral load. And again, having a patient series showing no adverse effects of note for 3 mg/kg over five days is quite an important finding.
[-] SwiftJustice88 | 1 points
Color me confused on this one, are some people’s bodies just responding differently to the same dose? If so it would be interesting to know what outside factors increase plasma levels.
[-] FoolsAndMoney | 2 points
From the paper:
" IVM plasma concentrations 160ng/mL were measured in 9 (45%) patients included in the efficacy analysis population. In another trial using a 3-day regimen of 0·6mg/kg for mosquitocidal activity and malaria control among adults, median Cmax (CI95%) was 119ng/mL (45-455).8 Diet is a key variable affecting the oral bioavailability of IVM, with increased plasma concentrations achieved with fed state, mostly related to the fat content of the meal; still other variables probably play significant roles since IVM is characterized by a high intra and interindividual variability in key PK parameters .21,22 The interaction of IVM with ABC transporters as P-glycoprotein 23 and the modulation of P-glycoprotein activity after oral This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3714649 18 administration is well known.24 Thus, variable constitutive and/or induced level of expression and activity of intestinal P-glycoprotein in treated patients, may have contributed to the observed large variability in the pattern of IVM absorption and systemic exposure. "
I have read elsewhere that the bio-availability of Ivermectin can be increased 2.5 times with a high fat meal over a fasted state.
[-] TrumpLyftAlles | 1 points
Nice catch.
Note to ivermectin researchers: define a regimen so all IVM recipients get similarly-fatty meals.
[-] No-Sandwich-777 | 1 points
A burger and a beer, then shut off alcohol consumption.
[-] No-Sandwich-777 | 1 points
Another low p group, btw.
[-] Ok-Film-9049 | 3 points | Nov 11 2020 23:38:27
Splitting the IVM group could introduce a confounders e. g the lower IVM conc may have poor health and things aren't working well. Maybe IVM is acting to stop the thrombi and fibrosis in the lungs as its main action. This may be what kills people, not lots of virus or dead virus.
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[-] akaariai | 4 points | Nov 12 2020 16:27:43
Splitting the group means also viral clearance was significantly slower in low IVM plasma group compared to control! That doesn't make much sense so the confounding factor seems more likely possibility (or the truth that if you play with the data enough you'll find something significant).
Seem likely IVM's mechanism of action (if any) is something different than pure virus clearance.
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[-] TrumpLyftAlles | 1 points | Nov 12 2020 23:55:11
Seem likely IVM's mechanism of action (if any) is something different than pure virus clearance.
I like this.
A Bangladesh trial focused on days to PCR- with ivermectin + doxycyline. IIRC 83.6% of patients went PCR- by day 6. Those on HCQ + AZT had a lower percent (81.X?) cleared on day 12. In that study, I thought clearing the virus was well established.
This study didn't include doxycycline.
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