Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection
Klimke et al.,
Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after..,
Med. Hypotheses, doi:10.1016/j.mehy.2020.109783
Proposal to use HCQ as an aerosol in order to reach sufficient therapeutic levels at the alveolar epithelial cells. Authors suggest this will reduce adverse drug reactions compared with oral application, and the increase in tolerability enables a broader use for prevention and post-exposure prophylaxis, which would be an advantage especially for high-risk, multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application is presented, showing inhalation was well tolerated.
Klimke et al., 27 Apr 2020, peer-reviewed, 4 authors.
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Medical Hypotheses 142 (2020) 109783
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Hydroxychloroquine as an aerosol might markedly reduce and even prevent
severe clinical symptoms after SARS-CoV-2 infection
T
⁎
A. Klimkea,b, , G. Hefnerc, B. Willd, U. Vossa,e
a
Vitos Klinikum Hochtaunus, Friedrichsdorf, Germany
Heinrich Heine University Duesseldorf, Germany
c
Klinik für Forensische Psychiatrie, Vitos Rheingau Eltville, Germany
d
Rheinische Friedrich-Wilhelms-Universität Bonn, University Hospital (UKB), Germany
e
Goethe-Universität Frankfurt am Main, Abt. Allgemeine Psychologie II, Germany
b
A R T I C LE I N FO
A B S T R A C T
Keywords:
COVID-19
Hydroxychloroquine aerosol
Pharmacotherapy
Prevention
SARS-CoV-2
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 h 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..
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