Hydroxychloroquine, Azithromycin in the Treatment of Covid-19

There is a critical need to identify effective treatments and a number of molecules have been
suggested, but The investigators still do not have enough evidence about their efficacy, to
treat COVID-19 pneumonia.

One of the most tested treatments was the use of Chloroquine or Hydroxychloroquine associated
or not to azithromycin.

Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. It's
known to block virus infection by increasing endosomal pH required for virus/cell fusion, as
well as interfering with the glycosylation of cellular receptors of SARS-CoV. It's also
demonstrated that CQ functioned at both entry, and at postentry stages of the 2019-nCoV
infection in Vero E6 cells. Besides its antiviral activity, CQ has an immune-modulating
activity, which may synergistically enhance its antiviral effect in vivo.

However, evidence regarding its effects in patients is limited. Among patients with COVID-19,
the use of Hydroxychloroquine (HCQ) could significantly shorten time to clinical recovery
(TTCR) and promote the absorption of pneumonia. This result has been presented in a
randomized controlled trial using two arms HCQ versus conventional treatment. The beneficial
effect of HCQ has been proven among mild severity COVID-19 pneumonia but the sample size of
this study was limited to 31 patients in each group.

Gautret et al also reported that HCQ treatment is significantly associated with viral load
reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. A
study showed that azithromycin concentration in phagocytic cells is 40× to 150× higher than
plasma concentrations. However, Gautret study has many limitations including selection biases
because of non-randomization, a small sample size, and dropout of six patients from the
study.

In terms of treatment duration, there is no study supporting a long course treatment of 10
days versus a short course treatment of 5 days for HCQ. This treatment is known to have a
large distribution volume of 73 l/kg and a plasma half life going from 22 days to 123 days.
This suggests that a short course treatment of Hydroxychloroquine and/or azithromycin could
be as effective as a long course treatment.

On the other hand, there are currently no effective specific antivirals or drug combinations
supported by high-level evidence, and The investigators don't know if HCQ could be effective
or if it's effectiveness may be improved if it's associated with Azithromycin. In fact, this
association can lead to improve pneumonia but can also increase the risk of treatment side
effects.