Drug combination can be life-saving in Covid-19, say new international guidelines

Drug combination can be life-saving in Covid-19, say new international guidelines

An international panel, led by the University of Dundee’s Professor James Chalmers, has recommended a combination of two drugs that can reduce the complications of Covid-19 by up to 40%.

Professor Chalmers and colleagues from nine other countries have produced best-practice guidelines for the treatment of hospitalised Covid-19 patients based on an analysis of thousands of studies around the world.

The guidelines, developed by the European Respiratory Society (ERS), recommend that the rheumatoid arthritis drug tocilizumab should be used along with the steroid dexamethasone, already widely in use in hospitals, when patients require oxygen or ventilatory support. They also strongly advise against the use of hydroxychloroquine and a number of other drugs to treat Covid-19.

The panel recommend that all patients should receive blood thinning treatments to prevent blood clots and that, where possible, doctors should use alternatives to ventilators such as high flow oxygen or tight-fitting face masks.

During the early stages of the pandemic, antiviral and anti-inflammatory drugs such as hydroxychloroquine, lopinavir-ritonavir and remdesivir were widely used to treat patients. The malaria drug hydroxychloroquine received widespread attention due to the advocacy of world leaders and remains a common form of treatment in many parts of the globe.

Despite this, the ERS panel found no evidence of significant clinical benefits associated with hydroxychloroquine, but did record a high risk of side effects, leading them to advise against this intervention.

The panel also recommended against using the HIV drug lopinavir-ritonavir, the antibiotic azithromycin and the gout drug colchicine. The anti-viral medication remdesivir, which was widely used across the UK last year, is also now not recommended. Further recommendations for research were made in areas where the evidence base was not strong.

Professor Chalmers said, “In the initial scramble to find ways of treating this horrible new disease and, ultimately, save lives, doctors were forced to deploy drugs in the absence of formal guidelines or evidence.

“Because of the contribution of research participants across the world, we now have two drugs that can save lives in hospitals. Knowing what doesn’t work is also very important to avoid wasting time and also putting patients at risk of side effects.

“That is certainly the case with hydroxychloroquine, which perhaps 60-70% of hospitalised patients receive in some countries. Hydroxychloroquine has become something of a celebrity of the drug world and we clinicians are regularly asked by patients and relatives why we are not using it because they have read on the internet that it cures Covid.

“The answer is clear – not only did a vast pool of scientific studies find that hydroxychloroquine does not help Covid-19 patients, it may even be harmful to them. Many Covid patients around the world have not been getting evidence-based care and we hope these guidelines will go a long way to improving this.”

The research does not address in detail the management of Covid-19 in the community, as most of the evidence obtained relates to hospitalised patients. An estimated 5% of Covid-19 patients who experience symptoms require hospitalisation, while up to a quarter of patients admitted to hospital will die of the virus.

The guidelines published by the ERS and endorsed by the Chinese Thoracic Society incorporate data obtained from a comprehensive and systematic literature review of the most recent studies. Health professionals are encouraged to take the guidelines into account in their clinical practice. As this is a living guideline, new areas of Covid-19 management will be addressed while those already covered will be updated when new research becomes available.

Of particular concern are patients who experience respiratory failure and require assistance breathing. The panel recommends non-invasive oxygen treatment, such as the use of tight-fitting face masks, in the first instance and that intubation and mechanical ventilation should only be used when patients fail to respond to a non-invasive approach.

“Reducing the need for invasive ventilation would be highly advantageous,” continued Professor Chalmers. “ICU resources have been overwhelmed at different stages of this pandemic so we need to be sure that we are using them in the way that will benefit the greatest number of patients. The evidence now supports the strategy of providing patients with non-invasive breathing support to try and prevent the need to go on a ventilator.”

Professor Nicolas Roche, ERS Guidelines Director, said, “For scientific societies, as for the Society as a whole, the Covid-19 pandemic underlined how the ability to react quickly to emerging conditions is crucial. In such situations, the initial lack of evidence is followed by a rapidly progressive influx of literature, making it difficult for clinicians to identify the most optimal options.

“To help caregivers, the ERS decided to produce consensus-based guidance initially, followed by evidence-based clinical practice guidelines. These were developed following a fast-track process in a six-month timeframe, despite the constant flow of new evidence on the nine specific therapeutic topics that were addressed. Thanks to the great efforts produced by the team and the ERS office, clear and up-to-date guidelines have been produced, which should be extremely useful to clinicians”.

‘Management of Hospitalized Adults with Coronavirus Disease-19 (COVID-19) : A European Respiratory Society Living Guideline’ is available at https://doi.org/10.1183/13993003.00048-2021.