The SARS-CoV-2 pandemic was declared by the World Health Organization (WHO) on March 11, 2020. The SARS-CoV-2 infection causes COVID-19. Doctors initially did not know how best to treat patients with COVID-19. Thus, in the first few months, clinical care was dominated by opinion, anecdotes and dogma. An example is the hype surrounding hydroxychloroquine as a potential cure for COVID-19. It took a huge global effort to prove that hydroxychloroquine does not benefit COVID-19 patients. One year on, there is still rampant misinformation on cures for COVID-19, with steam inhalation, multivitamins, mineral supplements, and drugs such as ivermectin, and chloroquine, all of which have not been demonstrated to treat COVID-19, still being prescribed.
Clinical trials
High-quality evidence that informs best practice for treatments comes from randomised clinical trials. Until these trials produced results, what doctors did was treat symptoms and provide life support. Treatments include oxygen, breathing support in the form of mechanical ventilation in severely ill patients, and supporting other vital organs such as kidneys with dialysis and heart with blood pressure medications. Many COVID-19 patients developed blood clots and were therefore treated with blood thinning medications.
COVID-19 was a clarion call for generating such high-quality evidence at pace, in particular designing trials to test multiple treatments simultaneously with innovative designs such as platform trials and adaptive trials. The RECOVERY trial network in the U.K., the REMAP-CAP trial globally focusing on critically ill patients, and the WHO-led SOLIDARITY trial globally are examples of this approach. RECOVERY demonstrated the lack of benefit with hydroxychroloquine, azithromycin, lopanivir-ritonavir, colchicine and convalescent plasma. REMAP-CAP highlighted harm with use of hydroxychroloquine and lopanivir-ritonavir and demonstrated that there is no benefit with convalescent plasma. SOLIDARITY also highlighted the lack of benefit from many of these drugs, including Remdesivir, an antiviral drug that perhaps shortens the illness duration. It is important that lack of benefit of these drugs reported in well-conducted clinical trials should be translated into clinical practice by healthcare professionals managing COVID-19 patients.
Drugs that work
Let us also consider the drugs that have been proven to benefit COVID-19 patients. We have learnt that corticosteroids (dexamethasone) is effective in COVID-19 patients who need oxygen and in critically ill patients (hydrocortisone). These cheap and universally available drugs have saved thousands of lives. More recently, we have emerging evidence that two interleukin-6 receptor blocking drugs (tocilizumab and sarilumab) benefit COVID-19 patients, including enhanced benefit when used in combination with corticosteroids, particularly in patients with moderate and severe COVID-19. It is important to note the emerging evidence with heparin (a blood thinning medication). Heparin possibly harms critically ill COVID-19 patients whilst potentially benefiting non-critically ill COVID-19 patients. Therefore translating these high-quality evidence into clinical practice by healthcare professionals would involve administering corticosteroids and interleukin-6 receptor blocking drugs when treating COVID-19 patients who are moderate to severely ill as per the WHO clinical criteria. Indiscriminate use of steroids and blood thinners in mildly ill patients with COVID-19 who do not need oxygen or any other organ support must be avoided.
The pandemic continues to exert pressure on healthcare systems. It is important that apart from supportive care (oxygen, ventilatory support), the only drugs shown to reduce mortality are steroids and interleukin-6 receptor blocking drugs. Do not prescribe ineffective treatments to patients with COVID-19.
A.V. Ramanan is Professor of Paediatric Rheumatology, University Hospitals Bristol NHS Foundation Trust, and M. Shankar-Hari is Professor of Critical Care Medicine, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London
