More evidence that hydroxychloroquine plus azithromycin dramatically improves COVID-19 outcomes

Here is a link to the latest paper from the French Doctor you have heard about and his collaborators.

The title is: "Clinical and microbiological effect of a combination of hydroxychloroquine and
azithromycin in 80 COVID-19 patients with at least a six-day follow up: an
observational study".

Randomized clinical trials are great - but there are other kinds of evidence that change the probability of efficacy, too.

Here is the paper's Discussion section.

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COVID-19 poses two major challenges to physicians.

The first is the therapeutic management of patients. In this context, it is necessary to avoid a
negative evolution of pneumonia, which usually occurs around the tenth day and may result in
acute respiratory distress syndrome, the prognosis of which, in particular in the elderly, is
always poor, whatever the cause. The primary therapeutic objective is therefore to treat people
who have moderate or severe infections at an early enough stage to avoid progression to a
serious and irreversible condition. By administering hydroxychloroquine combined with
azithromycin, we were able to observe an improvement in all cases, except in one patient who
arrived with an advanced form, who was over the age of86, and in whom the evolution was
irreversible. For all other patients in this cohort of 80 people, the combination of
hydroxychloroquine and azithromycin resulted in a clinical improvement that appeared
significant when compared to the natural evolution in patients with a definite outcome, as
described in the literature. In a cohort of 191 Chinese inpatients, of whom 95% received
antibiotics and 21% received an association of lopinavir and ritonavir, the median duration of
fever was 12 days and that of cough 19 days in survivors, with a 28% case-fatality rate (18).
The favourable evolution of our patients under hydroxychloroquine and azithromycin was
associated with a relatively rapid decrease in viral RNA load as assessed by PCR, which was
even more rapid when assessed by culture. These data are important to compare with that of
the literature which shows that the viral RNA load can remain high for about three weeks in
most patients in the absence of specific treatment (18;22) with extreme cases lasting for more
than a month. A study conducted in 76 Chinese COVID-19 in patients showed that high viral
RNA load is associated with the severity of the disease (23). Furthermore, in a study
conducted on a small group of 16 Chinese COVID-19 inpatients, viral RNA was positively
detected in 50% of them, after resolution of symptoms for a median duration of 2.5 days and a
maximum of eight days (24). Therefore, the rapid decrease in viral RNA load is one element
suggesting the effectiveness of this treatment. Furthermore, to our knowledge, the
measurement of viral culture during treatment was also evaluated for the first time. The fall in
culture positivity from the 48th day is spectacular, although, in a relatively small number of
cases, some people maintain a positive culture. 

 
The second challenge is the rapid spread of the disease in the population through contagious
individuals. The elimination of viral carriage in the human reservoir of the virus has recently
been recognised as a priority (25). To this end, the rapid negativation of cultures from
patients’ respiratory samples under treatment with hydroxychloroquine plus azithromycin
shows the effectiveness of this association. In addition, and in parallel to this study, we
evaluated in vitro the association of hydroxychloroquine and azithromycin on SARS-CoV-2
infected cells, and showed that there was a considerable synergy of these two products when
they were used at doses which mimic the concentrations likely to be obtained in humans
(https://www.mediterranee-infection.com/pre-prints-ihu2/). Thus, in addition to its direct
therapeutic role, this association can play a role in controlling the disease epidemic by
limiting the duration of virus shedding, which can last for several weeks in the absence of
specific treatment. In our Institute, which contains 75 individual rooms for treating highly
contagious patients, we currently have a turnover rate of 1/3 which allows us to receive a
large number of these contagious patients with early discharge.

 
Chloroquine and hydroxychloroquine are extremely well-known drugs which have already
been prescribed to billions of people. Because of anecdotical reports of heart complications
with such drugs in patients with underlying conditions, it would be useful to perform an ECG
before or at the very beginning of the treatment (26). This problem is solved by hospitalising
patients at risk with multiples pathogens in continuing care units with ECG monitoring
allowing for the early detection and treatment of these rare but possible cardiac side-effects.
Azithromycin is the drug that has been the most widely prescribed against respiratory
infections and a recent (2010) study showed that one in eight American out-patients, has been
prescribed azithromycin (27). Indeed, there have probably been more than a billion
azithromycin prescriptions around the world since it was first discovered. The toxicity of each
of these two drugs does not, therefore, pose a major problem. Their possible toxicity in
combination has been suggested in a few anecdotal reports but, to our knowledge, has never
been demonstrated. 

In conclusion, we confirm the efficacy of hydroxychloroquine associated with azithromycin
in the treatment of COVID-19 and its potential effectiveness in the early impairment of
contagiousness. Given the urgent therapeutic need to manage this disease with effective and
safe drugs and given the negligible cost of both hydroxychloroquine and azithromycin, we
believe that other teams should urgently evaluate this therapeutic strategy both to avoid the
spread of the disease and to treat patients before severe irreversible respiratory complications
take hold.