When I was commissioned to write a few lines on the possible efficacy of a novel treatment for coronavirus with the combination of Hydroxychloroquine and Azithromycin proposed by Dr. Didier Raoult and his team of infectologists at the Mediterranee Hospital in Marseille (1) less than a week ago, it coincidentally became the subject of several controversies on social networks.
Didier Raoult’s therapeutic protocol, soon to be published in the International Journal of Antimicrobial Agents, consisted of administering hydroxychloroquine 600mg per day, monitoring viral load by daily PCR in patients, and adding Azithromycin 500 mg/day on the third day, if there was no response.
What was achieved in the study of Hydroxychloroquine together with Azithromycin?
This results in three groups of patients, unfortunately very small in number, but which allow to be expressed in a curve graph, which describes the evolution of the viral load (PCR) in patients who were administered the two drugs, in patients who received only hydroxychloroquine, and in the control group.
In this experimental treatment, in addition to being debated by colleagues involved in the epidemic, the results were also disseminated by President Trump, igniting controversies, more against than in favor, from the director of the CDC in Atlanta, base, etc. to various experts and opinionators on social networks.
Hydroxyloroquine, a drug already used for arthritis and malaria, but also in other epidemics.
The use of Hydroxychloroquine has a strong rationale or basis, since it is a drug known since 1934, with extensive experience in application in long-term treatments, such as rheumatoid arthritis and malaria, available and very cheap. There is, in addition, previous experience, albeit limited, of such therapy in SARS1 (Severe Acute Respiratory Syndrome) infections in 2002 and MERS (Middle East Respiratory Syndrome) in 2012. But, above all, there is a paper published in 2005 (2) where, with in vitro experiments, it demonstrates the virucidal power of Hydroxychloroquine.
Azithromycin was added somewhat intuitively, based on its antibiotic, immunomoderator and anti-cytokine effect.
How does COVID-19 manifest itself and what does this study involve?
COVID-19, which we have had to learn quickly from patients and in the medical literature (about 1,000 publications in PubMed), seems to have three forms of expression, although there are cases in which the infection is practically asymptomatic:
- The pseudo-flu form, which occurs in 80% of cases, with fever, dry cough, asthenia and some case has been described with anosmia, or with abdominal pain and diarrhea. The flu picture is self-limiting and cures in most cases.
- The pneumonic form, which occurs in 15% of cases, is preceded by the pseudo-influenza form, with severe respiratory involvement, most frequently bilateral.
- Evolution of the pneumonic form to acute respiratory distress syndrome (ARDS), which affects 5% of cases, with a high risk of morbidity and mortality.
A therapeutic protocol such as that of the Marseilles school therefore seems consistent, in order to try, from the outset, to block viral progression.
The trials carried out at the beginning of the epidemic in Wuhan are being published and, at present, more than thirty trials are underway worldwide, which may increase tenfold in a few days.
Different drugs with different rationales have also been used, both in our hospitals and in hospitals in other countries:
- Kaletra (Lopinavir + Ribonavir), protease inhibitor.
- Oseltamivir, for neuraminidase inhibitor.
- Remdesivir as antiretroviral.
- Interferon B, as a non-specific antiviral.
- Corticoids, for their anti-inflammatory effect in patients in distress or at high risk of distress, an indication that has been fully recovered at the last minute.
- Tocilimulab as anti-interleukin 6, also in cases of distress.
- Sirolimus as m-TOR inhibitor.
Therefore, although with weak evidence, but with no other better demonstrated option, the protocol would be to start with 600mg of Chloroquine and 500mg of Azithromycin for 6 days, in patients with confirmed diagnosis in the early pseudo-influenza stages and in confirmed asymptomatic contacts.
Sources:
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial 2. Gautret P1, Lagier JC2, Parola P1, Hoang VT3, Meddeb L4, Mailhe M4, Doudier B4, Courjon J5, Giordanengo V6, Vieira VE4, Dupont HT2, Honoré S7, Colson P2, Chabrière E2, La Scola B2, Rolain JM2, Brouqui P2, Raoult D8. Int J Antimicrob Agents. 2020 Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949. [Epub ahead of print]
2. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Vincent MJ1, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, Seidah NG, Nichol ST. Virol J. 2005 Aug 22;2:69.
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