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Nitric Oxide Spray... a cure for COVID19??

by shminux1 min read15th Mar 202111 comments

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Covid-19
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According to https://www.biospace.com/article/releases/uk-clinical-trial-confirms-sanotize-s-breakthrough-treatment-for-covid-19/  

Patients with a self-administered nasal spray application found to have reduced SARS-CoV-2 log viral load by more than 95% in infected participants within 24 hours of treatment, and by more than 99% in 72 hours.

Update: the link to the company's site: https://sanotize.com/covid-19/

This sounds too good to be true, but says it's been RCT'd. What are the odds that by using a nasal spray for 3 days once you get positive test results, or even once you have symptoms would protect you from complications?

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Is the source legitimate? The article isn't an actual paper it reads like a scammy ad for the product. With red flag words like referring to nitrous oxide as a "nano molecule". Technically correct but in context we wouldn't call a simple small molecule a form of nanotechnology, when the word is used we mean complex atomic scale structures.

I mean if it were legit, I am thinking how the flu and common cold would be vulnerable to the same mechanism.

The linked site appears to be down, which is definitely not making this seem more trustworthy.

EDIT: I guess that's just one random site with the press release.

Interestingly, the clinical trial seems to be pre-registered: https://clinicaltrials.gov/ct2/show/NCT04443868 Not sure how much I should infer from that about how good it was.

1Gerald Monroe2moThat's a piece of evidence that there even was a real clinical trial and not random lies typed onto the internet. So maybe there is something here. I'm just noting the inverse - if this worked, was it always this easy? The flu and the cold have taken away a lot of lives and caused bad periods in countless more. All it took was huffing some toxic gas as a spray?

The pharma research company appears to be very real https://sanotize.com/covid-19/

I read the clinical trial registration and it seems like there's a lot of Goodharting going on when you pass this off as a cure for COVID-19.

From the preregistration it's interesting what endpoints they have. The primary endpoint is "Measure the efficacy of NONI compared to saline placebo control to shorten the duration of COVID-19 viral infectivity".

That sounds to me like the idea is if you put the stuff in your nasal pathways then you kill the virus in the nasal pathways and as a result it's less likely that you infect other people.

In the list they have as outcomes: 

3. To Measure the efficacy of NONI in prevention of progression of COVID-19 [ Time Frame: 28 days ]

Measure the proportion of subjects requiring hospitalization or ER/ED visits for COVID-19/flu-like symptoms

4. To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life (QoL) in subjects with COVID-19 [ Time Frame: 6 days ]

5. To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life in subjects with COVID-19 

The press release doesn't seem to indicate that they found a statistical significant result on either of those outcomes and I would expect that they would have put it into the press release if they found it. 

This suggests the treatment might make you less infectious to other people but at the same time it doesn't provide clinical benefits to the person being treated. 

It might be clinically useful to be able to reduce the infectiousness of patients but that's far from a cure for COVID-19.

Not implausible, similar RCTs exist for other nasal sprays ( But it would be important to know how many hours after application of the spray viral load was measured). This is for iota-carrageenan from a month ago, and widely available in some European countries. 

"In the multicenter, randomized, double-blind, controlled CARR-COV-02 study, 394 healthcare staff were randomly assigned to receive iota-carrageenan nasal spray (N = 199) or placebo (N = 195) four times per day. [...]The percentage of participants that developed COVID-19 was significantly lower in the group that received the iota-carrageenan spray compared to placebo (1.0% vs 5.1%, respectively; relative risk reduction for disease of 80.4 %; 95 % CI = 25-95 % )."   

 

 But it would be somewhat surprising if it were to protect you from complications once you are actually infected, as viral load in the throat or lungs would not be reduced. 

https://www.marinomed.com/en/news/marinomed-biotech-ag-announces-clinical-trial-at-swansea-university-medical-school-to-investigate-efficacy-of-carragelose-in-preventing-covid-19-infections

It might help if you have an infection in your nasal pathways to prevent that infection from spreading to other body parts. 

1MichaelLowe2moYes, but only if you do it early enough. By the time you are PCR positive I would assume it is already too late.
2ChristianKl2moYes. Maybe it still manages to reduce the amount of COVID-19 in the nose (and that's what the standard PCR tests measure) and thus would produce a false result.
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It's worth noting that this is a very similar treatment as Taffix/Nasaleze. The substance that's supposed to kill the virus in the mucus system is different but otherwise it's about spraying something into your nose that kills virus in there. 

I don't know how plausible the mechanism of action is here, but it's interesting that Scott mentioned nitric oxide being generated from sunlight as a potential confounder with Vitamin D effects in his COVID/Vitamin D post:

The loose ends that bother me the most are the seasonal pattern, the latitude data, plus the increased risk of hospitalization and death in Asians. I don't have a great explanation for those. One possibility is that sunlight does help prevent coronavirus, it just isn't Vitamin D mediated. I suspect that the "anything involving sunlight is Vitamin D" assumption a lot of epidemiologists have isn't going to hold up very well - this seems especially true for cancer, where sunlight matters a lot but study after study has shown Vitamin D doesn't help at all. It may also be true for schizophrenia, although I'm going off one really pathetic study there and it could very well turn out to be Vitamin D after all. Some people are doing a little bit of work to clear up what the sunlight-related-Vitamin-D-independent pathways might be; I think nitric oxide has come up a few times.

This would explain the failed RCT and Mendelian randomization. But if it were true, we would expect to see more of a correlation in observational data - the people with more nitric oxide (or whatever) would be the people who get the most sunlight would be the people who have the most Vitamin D.

I've been taking l-arginine (gets converted to nitric oxide in the body) for various reasons including this.