Chloroquine was identified in February as a drug with potent in vitro activity against SARS-CoV-2, and its analog hydroxychloroquine also demonstrated in vitro activity in March. These are both antimalarial drugs with anti-inflammatory and immunomodulatory activities.

 

These drugs were used to treat COVID-19 in China as early as February, with a small study from France indicating reduction in viral load (in association with azithromycin) and good prospects, despite the study’s methodological limitations. Further studies in France and the USA, the latter of which included the association with azithromycin, did not provide clear conclusions, tending towards no statistically significant differences in efficacy compared to standard of care being demonstrated in randomized studies.

 

Many clinical trials were established all over the world, including the Solidarity clinical trial run by the WHO, with few having been properly reported as of yet. As the pandemic spread, hydroxychloroquine and chloroquine were also included in COVID-19 treatment guidelines emitted by authorities in several countries, including Portugal, Spain, Brazil, Italy, among others. These guidelines caution the use of these drugs and recommend in-hospital monitoring, due to the well-known safety issues associated to these drugs, including cardiac risks related to its QT interval-prolonging effect.

 

On 22 May, The Lancet published a multinational registry analysis of over 96 000 patients from 671 hospitals all over the world, conducted by the private company Surgisphere, finding not only no benefit in the use of these drugs to treat COVID-19, but also decreased in-hospital survival.

 

This led to the temporary pause of the hydroxychloroquine arm of the WHO Solidarity trial on 27 May in order to reassess and review the safety data. Following suit, in the next few days, several countries revoked authorizations or recommended suspension of use, including Portugal and France. However, countries like Spain and Brazil made no such changes. The latter country had just published guidelines recommending the out-of-hospital use of hydroxychloroquine+azithromycin on 20 May.

 

On 3 June, a letter of concern was published, expressing the concern of multiple scientists in regards to the origin and validity of the data of the observational study published by The Lancet on 22 May.

 

In the meantime, the WHO, who had just temporarily paused the hydroxychloroquine arm of the Solidarity trial as mentioned above, announced on 3 June, only a week later, that, based on the available mortality data, the trial would resume after all and without changes to the protocol.

 

As Surgisphere, a company with questioned competencies for this type of analysis, was unable to provide the full data set for independent third-party review due to confidentiality requirements and client agreements, the study was retracted by its authors on 5 June.

 

The need for quality clinical research is of paramount importance in providing the best care in a timely fashion for COVID-19 patients all over the world.

 

Melanie Salgado

Pharmacist and Medication Content Analyst

ALERT Life Sciences Computing