Recommended Use: Hydroxychloroquine, 200 mg three times per day for 10 days and Azithromycin, 500 mg once daily for ten days

Both chloroquine and hydroxychloroquine have been reported to inhibit SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more potent antiviral activity [1].

Chloroquine is included in Chinas National Health Commission treatment guidelines. As per available evidence it has been suggested that the drug is associated with the reduced progression of disease and duration of symptoms [2, 3]. However, primary data supporting these claims have not yet been published [4].

In an open-label study of 36 patients with COVID-19, use of hydroxychloroquine (200 mg three times per day for 10 days) was associated with a higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with no specific treatment (70 versus 12.5 percent) [5].

The same study showed that the use of azithromycin in combination with hydroxychloroquine led to additional benefits, but there are certain methodologic concerns about the control groups included in the study, and the rationale for using azithromycin in this setting was ambiguous.

Even though there is limited availability of clinical data, the relative safety of short-term use of hydroxychloroquine (with or without azithromycin), the lack of known effective interventions, and the in vitro antiviral activity, still some clinicians are of the view that it is reasonable to use one or both of these agents in hospitalized patients with severe or ‘at risk’ for severe infection, particularly if they are not eligible for other clinical trials.

Marseille study has been registered on 5th March in the European Union Clinical Trials Register and approved by the National Medicines Safety Agency (ANSM). The study methodology may include up to 25 COVID-19 positive patients, including five participants between 12–17 years of age; 10 participants aged 18–64 years, and 10 participants more than 65 years.

The study is anon-blinded trial where a strong reduction in viral load with hydroxychloroquine was observed. At the end of 6-day treatment with hydroxychloroquine percentage of patients with confirmed COVID-19 testing was reduced to 25% as compared to 90% reduction in those not receiving any treatment.

In addition, when three groups of patients were compared; group 1 receiving no treatment, group 2 receiving hydroxychloroquine, and group 3 receiving hydroxychloroquine+azithromycin; the results showed that there was a significant reduction in number of positive cases in patients treated with combination therapy. In fact, it was seen that in patients receiving combination therapy for 6 days, the percentage of cases positive for COVID-19 was restricted within 5%.

Infectious disease experts have said that the addition of azithromycin has been justified as it is known to be effective against complications from bacterial lung disease as well as its effective action in the laboratory against a large number of viruses.

Christian Perronne, head of infectious diseases, University Hospital Raymond Poincaré, Garches, Parisopined, “I really believe in hydroxychloroquine. It is a drug I find rather fascinating, that has been used for decades. There have been positive results in an in vitro study and a preliminary Chinese study in 100 patients which showed that hydroxychloroquine reduced the viral load, the symptoms lasted for less time, and they are not as severe. This could reduce the number of carriers, which I find interesting from an epidemiological perspective.”

He also added that from an ethical point of view as well, monitoring of drug effects should be mandatory for all patients with severe disease who are admitted in hospital, are under surveillance, and even on short term treatment especially with respect to drugs that prolong QT interval. It may be possible that the patient may experience pain or fever as adverse effect when drug is given in increased doses, as per a Chinese study. However, so far the adverse effect of hydroxychloroquine has not been reported to be dangerous.

Resources:

1. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020.
2. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020; 14:72.
3. Colson P, Rolain JM, Lagier JC, et al. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020; 105932.
4. Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020.
5. Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 DOI:10.1016/j.ijantimicag.2020.105949.