et al., bioRxiv, doi:10.1101/2020.06.19.159053 (Peer Reviewed) (not included in the study count)
Animal study with Syrian hamsters, showing treatment of SARS-CoV-2-infected hamsters with favipiravir or HCQ (with and without AZ). Treatment with HCQ alone resulted in a very modest reduction of 0.3 log10 viral RNA copies/mg lung, and no reduction in viral RNA load in the ileum or stool.
Therapeutic levels of HCQ may not have been reached. Cytosolic concentrations in the lung were far below the EC90 target.
A number of issues have reportedly been raised, including the following, for which the authors did not respond:
- HCQ was administered with DMSO and Cremophor - why were non-neutral carriers chosen? DMSO has anti-inflammatory properties and Cremophor has a range of side effects : "use has been associated with severe anaphylactoid hypersensitivity reactions, hyperlipidemia, abnormal lipoprotein patterns, aggregation of erythrocytes and peripheral neuropathy". Why weren't the same amounts of solvent applied to the non-treated animals? Shouldn't favipiravir have been dissolved in the same way to avoid bias?
- Why is the method of administration different for both products (oral gavage/intraperitoneal injection)?
- One of the HCQ protocols used in France (IHU Marseille) prescribes 600mg of HCQ per day to patients. For a body weight of 60kg, this corresponds to a dose of 10mg/kg. How is a dose of 50 mg/kg in this study justified, i.e. 5 times more, with possible systemic effects on the animals and possible influence on the results?
- Why were the animals killed after 4/5 days and did the treatment not continue? Unfortunately, this does not allow us to know the real course of the disease or the mortality of the animals beyond day 4. Is it because the animals spontaneously improve without treatment as Professor Neyts seems to say in his webinar for the GVN? And if this is indeed the case, isn't the use of these hamsters exactly an objection as a model for COVID-19 research?
Kaptein et al., 6/19/2020, peer-reviewed, 35 authors.