Thread by @IngredientsbyL

@FurnessColin I think we should approach the results of the studies of NO nasal spray with caution. Here is the most recent one: thelancet.com/journals/lanse…

@FurnessColin The authors tested for viral clearance using RT-PCR of nasal swabs, ie. they could only determine "clearance of nasal viral RNA". However, SARS-CoV-2 infects the rest of the body - the nasal passage & respiratory tract is only the entry point.

@FurnessColin There's no way an NO nasal spray can prevent the spread of the virus to the rest of the body, also no way it can prevent viral persistence in the brain and other organs: nature.com/articles/s4158…

@FurnessColin "Recovery" in this study was defined as a negative Rt-PCR, ie, "clearance of nasal viral RNA", but that does not equal actual recovery from the virus lurking in other parts of the body.

@FurnessColin The study also says nothing about follow-up with study participants to identify markers of COVID infection, such as microclots, organ (brain/heart/lung) damage, and long Covid symptoms.

@FurnessColin We already know that how mild or severe symptoms were upon initial infection have little association with development of Long Covid; vascular damage and organ damage occurs regardless of symptoms of initial infection. pubs.rsna.org/doi/10.1148/ra…

@FurnessColin I also wish to point out that a key ingredient in the NO spray is hypromellose, a gelling agent. Hypromellose is used to form a gel that sticks to the nasal passage, allowing for extended release of NO, and keeping it in place (otherwise the spray would just drain off)

@FurnessColin However, the placebo is just saline & preservative (benzalkonium chloride, a quaternary ammonium surfactant). Hypromellose, or hydroxypropyl methylcellulose is a cellulose derivative that can form a gel with water, similar to carrageenan..

@FurnessColin There's a number of studies showing carrageenan nasal spray may have use against respiratory pathogens - it's been studied for at least the past 10 years e.g.: pubmed.ncbi.nlm.nih.gov/24219370/

@FurnessColin And more recently, iota-carrageenan spray as a prophylactic against COVID: pubmed.ncbi.nlm.nih.gov/34629893/

@FurnessColin The mechanism of action for iota-carrageenan is believed to be its ability to trap virus particles and prevent them from binding to and infecting cells. respiratory-research.biomedcentral.com/articles/10.11…

@FurnessColin (Another possible mechanism is carrageenan gel acting as a humectant, thus supporting the protective function of nasal mucus and the microbiome that exists in the nasal passage.)

@FurnessColin Anyway, given that hypromellose functions in a similar fashion to carrageenan to form an aqueous gel, this begs the question, is it the hypromellose or the NO that's providing the protective effect? We don't know as the placebo is just saline + preservative.

@FurnessColin There's already researchers looking at the possibility of using hypromellose nasal spray as a protective barrier against infection: pubmed.ncbi.nlm.nih.gov/34960612/

@FurnessColin Finally, in the NO nasal spray cited above, the study participants applied the spray 6x daily. That's a lot of spray solution needed, and as you said, once the bottle is opened, the shelf life is very short.

@FurnessColin A bottle of Enovid is 25 mL, ~$60 CAD, while a bottle of Betadine Cold Defence containing iota-carrageenan is 20 mL, ~$14. I wonder how these two would compare head-to-head in real-world usage, ie. not sprayed 6x daily?

@FurnessColin Regardless, for the price difference, I'd rather put that money towards N95/KN95 respirators & HEPA filters, things which will for sure work to cut transmission of airborne pathogens.

@FurnessColin I know everyone is looking for a magic bullet, but really, a nasal spray is going to be flawed from the outset: it has to be sprayed liberally and often, because its effect is temporary AND the entire nasal passage has to be coated (difficult to achieve).

@FurnessColin 1 more note: in Enovid, NO is generated by sodium nitrite in acidic solution. Under acidic conditions, sodium nitrite can react with 2ndary/tertiary amines to form nitrosamines, which are potentially carcinogenic. Perhaps I missed something but why is this issue not addressed?

@FurnessColin @threadreaderapp Please unroll