Hypothesis
Version 1
Preserved in Portico This version is not peer-reviewed
Hydroxychloroquine as an Aerosol Might Markedly Reduce and Even Prevent Severe Clinical Symptoms after SARS-CoV-2 Infection
Version 1
: Received: 5 April 2020 / Approved: 7 April 2020 / Online: 7 April 2020 (11:11:09 CEST)
A peer-reviewed article of this Preprint also exists.
Abstract
Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.
Keywords
COVID-19: hydroxychloroquine aerosol; pharmacotherapy; prevention; SARS-CoV-2
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (7)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment
Commenter: Dr. P. Mahesh Shanmugam
The commenter has declared there is no conflict of interests.
It is the need of the hour for pharmacology specialists and internists evaluate this mode of delivery considering its potential as prophylactic treatment and as addendum to life saving therapy.
Commenter: Dr.med. Herwig Lange
The commenter has declared there is no conflict of interests.
I hope, his idea is put to test in a trial.
Commenter:
The commenter has declared there is no conflict of interests.
Commenter:
The commenter has declared there is no conflict of interests.
Nebulizer (Adult), with aerosol mask, 7' (2,1 m) supply tube, female thread grip connector, elastic strap fixation. and 2) Mesh Nebulizer with bubble size < 5 um (usually used in the therapy of asthma with corticosteroid solutions)
Dosages:
A.K.: Day 1: 2 x 0.5 ml = 0.8 mg HCQ/d, Day 2-7: 2 x 1 ml = 1.6 mg HCQ/d – no side effects well tolerated, interval was 12 h
B.W.: Day 1: 1 ml = 0.8 mg HCQ/d, Day 2: 2x1 ml = 1.6 mg/d, Day 3-6: 2x2 ml = 3.2 mg/d, Day 7: 4 x 5 ml = 16 mg/d
Commenter:
The commenter has declared there is no conflict of interests.
We would be glad to help for free with our inhalation PBPK for HCQ
using our tools developed for US Pharma and FDA.
Andrzej.przekwas@cfdrc.com
Commenter: Alexey Kachan
The commenter has declared there is no conflict of interests.
I performed an experiment - dissolved pill of hydroxychloroquine in saline water (0.9%), removed sediment from solution (pill have many extra non-soluble components you shouldn't have to inhale) and inhale it via nebulaiser (about 5mg). I had felt nothing bad an the moment and further, so I knew - it has no side effects. It had bitter taste - that's it.
Two weeks ago (16.08.2020) my wife returned from trip with something like flu. At the moment I didn't know if it is COVID or just common cold - but I've started to make inhalation of aerosole of hydroxychloroquine according to mentioned scheme.
Twice per day, 5-10mg dissolved in 1-2 cm3, via nebulaiser.
After couple days we got tests from laboratory - it was COVID-19.
20-Aug-2020 I got my own first symptoms - it was sore bronchys, but not much. What was bad - it was my intestine, I was really ill for two days, and also headache. Temperature was 37.7 at one day, 37 at the next day. I had diet, so I recovered in few days, and then got rare dry cough.
In next few days I also got 100% deprivation of sense of smell.
It was quite interesting, because I lost it during two days, and first day I lost many smells, but not all of them. For example I didn't feel at all alcohol (etyl spirit), but feel sense of isopropilen. At the next day I lost all other smells.
All these days from the beginning I performed inhalation of hydroxychloroquine.
24-Aug-2020 I had test in lab and got positive result for COVID-19, so it's additional proof of nature of my disease.
Now I feel good, yesterday (31-Aug-2020) I did another test for COVID, this time it's negative. I still have deprivation of sense of smell, and rare dry cough, but all other things are good, and my SPO (oxygen) is 98%.
My conclusions :
1. Hydroxychloroquine as aerosol can't prevent you to get COVID-19.
2. It has no significant side effects.
3. It has no visible effects against virus, but it requires more statistics.
4. It has very clear antiflammatory effect : if you have dry cough (I still have it), hydroxychloroquine as aerosole immediately reduce sense of sore throat and sore bronchys. Dry cough just stops immediately. Quite interesting effect. Saline water without hydroxychloroquine don't have same effect.
5. I know nothing about long-term effect and can't recommend to do the same to anyone.
But you are free to use all this information at your risk.
This is my personal experiment with COVID-19.
Commenter: Betty Klein
The commenter has declared there is no conflict of interests.