(We recommend reading this post for information regarding basic concepts of evidence-based medicine relevant to recent discoveries about COVID-19)
Based on: Direct evidence of VERY LOW CERTAINTY and indirect evidence of LOW CERTAINTY.
The results of the studies carried out to date do not confirm any kind of benefits derived from the use of azithromycin or other macrolides for treating patients with COVID-19.
It is understandable that, when facing a new disease with no known treatment such as COVID-19, professionals may rush to identify the interventions that might lead to a cure. One of the proposals for COVID-19 patients is azithromycin. This drug is an antibiotic that belongs to the family of the macrolides, which are most commonly used for treating bacterial infections. The question of whether laboratory findings and evidence from research on other viral infections (indirect evidence) do or do not make azithromycin and other macrolides good candidates for treating COVID-19 patients could lead to a long discussion. The point, however, is that azithromycin has sparked great enthusiasm among scientists and authorities.
This enthusiasm is mostly explained by a non-randomised study conducted in France, released on March 19th, 2020, and read by our researchers via WhatsApp even before it was published in a scientific database. Within a few hours of its dissemination, it had already been critically analysed by several experts worldwide. There was consensus that the study showed severe methodological limitations, and questions about its scientific integrity have also been raised.
But is there any other evidence to add to the discussion?
What evidence tells us about the efficacy of macrolides for COVID-19
As members of the COVID-19 L·OVE Working Group, we performed an exhaustive search of studies that might answer this question. Based on the results we found, we can communicate the following:
- We confirm that the non-randomised study previously mentioned does not provide evidence useful to make any valid or trustworthy conclusions, necessary for decision-making.
- After a systematic search and review of the existing literature, we could not identify further studies in COVID-19 patients.
- We identified a single study, in patients with MERS-CoV infection, another coronaviral disease, which assesses the use of macrolides in hospitalised patients with MERS-CoV. It found that there were no differences neither in the effect on mortality nor the presence of the virus in respiratory secretions. Nevertheless, this study:
a. Constitutes a piece of indirect evidence, which can indeed be extrapolated, but does not provide the same certainty as direct evidence.
b. Presents a methodological design that is inadequate for the assessment of the effects of a treatment. For this reason, the certainty of the results is even lower.
Therefore, we concluded that, in order to determine the effects of the use of these antibiotics in COVID-19, further experimental trials are required, ideally, sound randomised trials with a sufficient number of patients, and following international quality standards.
Will we obtain new information about macrolides for COVID-19 in the near future?
We searched for ongoing studies assessing the use of macrolides in COVID-19 and found 5 officially registered trials. Four of these aim to assess the combined therapy of azithromycin and hydroxychloroquine, while the other will evaluate therapy with carrimycin (another macrolide) in comparison to antivirals or chloroquine. None of these studies has begun to recruit patients yet, so we can only state that, at least in the near future, there will not be evidence available to conclude whether it is effective or not to use azithromycin or other macrolides in the treatment of COVID-19 patients.
How can we make a good decision?
At the moment of making decisions, we need to balance the benefits and risks of every specific therapy. On one hand, we have the potential benefit of azithromycin or other macrolides in COVID-19, which is uncertain due to the limitations of the relevant studies. And, on the other hand, we have the secondary effects of the drug, which include diarrhoea and allergic skin reactions, although do not appear to be serious. These elements must be pondered according to the patients´ characteristics, besides ensuring a safe administration, supervised by health professionals.
In the context of the COVID-19 pandemic, it is crucial to consider the impact of indiscriminate use of antibiotics on bacterial resistance rates, and the need to use these drugs in the treatments of other infections, for which these drugs hold a proven efficacy. Additionally, we must consider the negative impact that inadequate prescriptions might have on an individual patient’s health, as well as on the economy of the healthcare systems of the affected countries.
As COVID-19 L·OVE Working Group, we understand that, all around the world, people handling COVID-19 patients are making important decisions which require trustworthy evidence. So we have ensured to update our systematic review as soon as new evidence emerges. For now, while we wait for the publication of the scientific paper with our findings, we will upload a preliminary report to our platform, with all the data necessary for an accurate analysis of risks and benefits of this therapy for COVID-19.
In this link to the L·OVE platform, you can keep updated with the new evidence collaboratively identified by our group, that we will be critically appraising and summarizing as soon as it emerges.