By Grant M. Gallager
In laboratory trials, hydroxychloroquine and chloroquine have shown antiviral effects against SARS-CoV-2. However, the clinical literature that emerged from their use among patients with coronavirus disease 2019 (COVID-19) has been much more ambiguous.
A recent review, published in the Annals of Internal Medicine by a team of researchers supported by the Healthcare Research and Quality Agency, sought to summarize the evidence on the benefits and harms of hydroxychloroquine and chloroquine as treatments or prophylaxis for COVID-19. The study team ultimately concluded that the evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting, along with a lack of empirical studies on their use as prophylaxis.
The study team was guided by a series of clinically relevant questions for the treatment of COVID-19:
1. Is hydroxychloroquine or chloroquine effective in treating children or adults with COVID-19 infections in any setting?
2. Is hydroxychloroquine or chloroquine effective in preventing SARS-CoV-2 or COVID-19 infections in children or adults?
3. What are the potential harms and adverse events associated with the use of hydroxychloroquine or chloroquine for the treatment or prevention of COVID-19 infection?
Data were reviewed from December 1, 2019 to May 8, 2020 and were collected through PubMed, Cochrane Library, EMBASE, Scopus, preprints, ClinicalTrials.gov, the World Health Organization's International Clinical Trials Registry Platform, bioRxiv and the China Clinical Trials Registry.
The selection criteria for the studies included articles in any language that reported efficacy or safety results for the two drugs in question, in any setting, in adults or children with suspected COVID-19 or at risk of SARS-CoV-2 infection. Several researchers performed independent data extractions and quality assessments.
Finally, 4 randomized controlled trials, 9 case series, and 10 cohort studies were identified for analysis of hydroxychloroquine treatment. No studies evaluating prophylaxis were available.
"The evidence was contradictory and insufficient regarding the effect of hydroxychloroquine on outcomes such as all-cause mortality, progression to severe disease, clinical symptoms, and virologic clearance from the upper respiratory tract by antigen testing," the study authors wrote.
Several articles in the review found that some patients who received hydroxychloroquine developed a QTc interval of 500 or more, although the proportion of patients with adverse effects varied.
There were two studies on the efficacy of chloroquine. One trial compared the highest dose (600 mg twice daily for 10 days) with the lowest dose (450 mg twice daily on day 1 and once daily for 4 days). The trial was stopped due to concerns that the higher dose therapy might have increased mortality and prolonged the QTc interval.
The other efficacy data for chloroquine came from an observational study. The study compared adults with COVID-19 who received 500 mg of chloroquine phosphate once or twice daily with patients who did not receive chloroquine. The results indicated a minor benefit in fever resolution and viral clearance.
Both drugs have been subject to immense media attention, both positive and negative. But for doctors, science likely hasn't resolved the issue enough to justify the widespread use of these controversial antimalarial medications.
" There were few controlled studies, and control was inadequate in the observational studies," the authors cautioned.
From: https://www.contagionlive.com/news/systematic-review-hydroxychloroquine-ambiguities