Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

Original: N Engl J Med. 2020 May 7

Author(s): Geleris J, Sun Y, Platt J et al

Reviewer: Stylianos Loukides, e-Learning Director

Published: 10 May, 2020

Chloroquine and hydroxychloroquine are widely used in the treatment of malaria and rheumatic diseases. Hypothetically, they have been suggested as effective treatments for coronavirus disease 2019 (Covid-19). The hypothesis was mainly based on both antiinflammatory and antiviral effects. However, despite their wide use as a first step treatment for COVID-19 infection several concerns have been raised which are mainly attributed either to the lack of a supportive well designed study or/and the safety issues mainly arisen from cardiovascular effects. Previous studies supported a beneficial effect but several concerns have been raised regarding methodology and number of study participants.

In this observational study the authors wanted to determine whether the use of hydroxychloroquine is associated with a lower risk of intubation and death. Proper adjustments to co-variates affecting the statistical model were performed.

1446 consecutive patients were initially recruited and 70 were excluded mainly due to early intubation or death within the first 24 hours. The remaining 1376 patients were followed up for 23 days and 800 of them received hydroxychloroquine (600 mg twice on day 1, then 400 mg daily for a median of 5 days). Interestingly half of them received the drug within 24 hours post admission and 85% within 48 hours.

346 patients (25.1%) had a primary end-point event (180 patients were intubated, of whom 66 subsequently died, and 166 died without intubation).

The use of hydroxychloroquine failed to show any beneficial effect regarding primary end point events. Similar results were observed in the multiple sensitive analysis.


  • In the unmatched patients, those received hydroxychloroquine had a lower PaO2/FiO2 ratio which means that the underlying severity was quite different.
  • Second, as the authors mentioned in the discussion, this was a single center study which means that we cannot generalize the results.
  • Finally, in the clinical setting we need to define whether the treatment interventions are targeting the mild to moderate or the severe and life threating disease.
Respiratory critical care
Respiratory digests
Respiratory infections