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Even cough syrup might actually work against Coronavirus

I didn’t think cough syrups even worked against coughs, but one new paper suggests that bromhexine in common cough syrups reduces both Covid-19 rates of ICU and of mortality.

The era of antivirals has come, not that Big Pharma want you to know that cheap out-of-patent drugs might help. But for years we were told that medical science didn’t have an answer to viruses.

Bromhexine was patented in 1961 and is commonly found in OTC pharmacy cough syrups with names like Bisolvon, Robitussin, and Duro-Tuss (Wiki has a long list).

Theoretically Bromhexine sabotages one of our molecules — with the snappy name of TMPRSS2 (which is shorter than saying Transmembrane protease S2).  A protease is a fancy pair of molecular scissors, it chops or tweaks the viral spike and if that doesn’t happen, the virus can’t get into the cell (at least not through its favourite path).

The nice thing about an antiviral acting against our  molecules, rather than against the virus itself, is that it’s harder for the virus to mutate to get around it. That means it’s less likely the virus can develop resistance. The downside of targeting our own molecules is that it might fritz things up. Presumably this protease does something useful sometime. To that end, mice that don’t have this protein at all, seem to do OK. And then, there is fifty five years of drug store sales. How bad can cough syrup be?

Bromhexidine, mechanism of action, TMPRSS2, Spike activation. diagram.

Bromhexidine, mechanism of action, TMPRSS2, Spike activation. diagram.

It is not at all certain that this drug would thwart the virus. Viruses can get into cells through another method called endocytosis. Possibly bromhexine might not make much difference.  Luckily for us, a group in Iran were desperate enough to try it in a small, but reasonable trial, and the results are enticing.

Basically, 39 people were picked at random out of 78 to try the bromhexine. In the half that missed out on Bromhexine, 11 went on to need ICU and 9 died. In the half who got the bromhexine, only 2 went into ICU and none died.

We might feel a bit sorry for the nine in the first trial that didn’t get lucky. We won’t know how unlucky until someone has done a bigger trial. For the moment the p value of avoiding ICU was 0.007. And a p value of 0.027 for avoiding death.

Where are the media?

This paper was published on July 19th. In a world full of journalists, doctors and a million interested onlookers all connected at the speed of light, it’s curious that it hasn’t garnered attention. At this point I can’t find a single news story mentioning these results. There is one Swiss  niche group which mentions it (at a dose of 50 – 100mg). And there is a $3,500 market report available from 2 days ago cryptically suggesting the “bromhexine market will grow a significant rate…”. Nearly every pharma company makes it. I’m curious to do this search now, because if the drug is useful, it will be near impossible to search in a few weeks and find “something that wasn’t there”. Not that I’m certain this drug is the answer, but years from now historians will be looking at how well the news got filtered.

There are a few mentions months ago in medical niche outlets (March 2nd),  clinical trials in China, and obviously some awareness that this drug might be useful. The wonder then, is that with all the billions being thrown at the virus, it was left up to an Iranian lab to pursue this possibility?

According to the Swiss group:

The efficacy of bromhexine in blocking cell entry of coronaviruses was established in 2017.

So we had a three year head start and yet, seven months into a global pandemic and almost no one has studied whether cough syrup might help? There are lessons in there for the ways we structure our research, and how useless our universities are.

And it seems frivolous, but Iran’s death toll peaked the week after this study was published and has declined since then. (There is a swamp of factors: It could be bromhexine, or treatment changes, vitamin D levels, a younger age group, or it could be that Iran doesn’t test enough people, and the true number of infections has declined, even though the official daily new cases is steady on 2,000 a day.) But if word is spreading and Iranian drug stores are running out of cough syrup that would be interesting. Anyone know?


Eyeballing table 1 of the paper there’s no obvious reason why the drug group would have done so much better. On average both groups waited about 7 to 8 days after symptoms showed up before going to hospital. Their blood oxygen was 88%. The treatment group may have been slightly less sick, with lower levels of lassitude, headache and tummy aches, was slightly younger (58 not 61) but had more diabetes.

The treatment group was given 8mg, three times a day. Imagine if they had started treatment as soon as they felt sick?

h/t thanks to TedM, who heard it from a Dutch doctor.

UPDATE: As TedM notes, Iran may be using low dose HCQ as standard and Bromhexine may only be useful in combination with HCQ:

In another publication from Iran on the trial is this comment: “Whether this promising result is because of bromhexine alone or combination of low dose HCQ [200 mg/d] and bromhexine is not clear at this point.”

200mg/d is half that in the Zelenko protocol. Both groups were on the 200mg/day HCQ, so it would appear that this dose of HCQ alone is too low to be effective.

The article here: http://www.immunopathol.com/Files/Inpress/ipp-14214.pdf


Ansarin et al, (2020) Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial, BioImpacts, 10(4), 209-215 doi: 10.34172/bi.2020.27 http://bi.tbzmed.ac.ir/

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