Higher dose corticosteroids associated with a 60% increased risk of death in hypoxic COVID-19 patients requiring only non-invasive oxygen therapy

Newswise —

A recent study, set to be presented at the upcoming European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2023) in Copenhagen from 15-18 April, and published in The Lancet, has revealed that using higher doses of corticosteroids to treat hypoxic COVID-19 patients who require only oxygen therapy or no breathing support, as opposed to standard care with low dose corticosteroids, is linked to a significant 60% higher risk of mortality.

The RECOVERY Collaborative Group, led by Prof Sir Peter Horby and Prof Sir Martin Landray from the University of Oxford, UK, previously conducted a study that demonstrated the efficacy of low-dose corticosteroids in reducing mortality for COVID-19 patients requiring oxygen or ventilatory support. Subsequently, starting from May 2021, the RECOVERY trial evaluated the use of higher doses of corticosteroids in this patient population. However, in May 2022, the independent Data Monitoring Committee recommended discontinuing this treatment assessment for patients who only required oxygen therapy or no breathing support. The trial is ongoing to further investigate the effects of high-dose corticosteroids for patients who require non-invasive or invasive mechanical ventilation.

The study enrolled adult patients with COVID-19 who met the criteria of having clinical evidence of hypoxia, including those receiving oxygen therapy or with oxygen saturation levels below 92% in room air. These eligible patients provided consent and were randomly assigned in a 1:1 ratio to two groups. The first group received usual care along with higher doses of corticosteroids, specifically dexamethasone at a dose of 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner. The second group received the usual standard of care alone, which included dexamethasone at a lower dose of 6 mg once daily for 10 days or until discharge if sooner. The primary outcome measured was 28-day mortality among all participants who were randomly assigned to either group.

Between May 25, 2021, and May 13, 2022, a total of 1272 patients with COVID-19 and hypoxia, out of which eight (1%) did not receive any oxygen and 1264 (99%) received simple oxygen only, were randomly assigned to receive either usual care along with higher dose corticosteroids (659 patients) or usual care alone (613 patients, with 87% receiving low-dose corticosteroids during the follow-up period). Among those randomly assigned, 745 (59%) were located in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. Out of the total, 248 (19%) had diabetes and 769 (60%) were male. The study found that 123 (19%) of the patients in the higher dose corticosteroid group and 75 (12%) of the patients in the usual care group died within 28 days, indicating a 60% increased risk of mortality in the higher dose corticosteroid group.

Additionally, the study found that there was an excess of pneumonia cases attributed to non-COVID infections in the higher-dose corticosteroid group, with 64 cases (10%) compared to 37 cases (6%) in the usual care group. Furthermore, there was an increase in hyperglycemia (high blood sugar episode) that required an increased insulin dose in the higher-dose corticosteroid group, with 142 cases (22%) compared to 87 cases (14%) in the usual care group. These findings suggest potential adverse effects associated with the use of higher-dose corticosteroids in patients with COVID-19 and hypoxia.

The authors of the study concluded that low-dose corticosteroids reduce the risk of death among hospitalized patients with COVID-19 who require oxygen or ventilatory support. However, among patients who only require simple oxygen, higher doses of corticosteroids were associated with an increased risk of death compared to low-dose corticosteroids. It remains uncertain whether the use of higher doses of corticosteroids is beneficial for patients requiring non-invasive or invasive ventilation, as the RECOVERY trial is ongoing and continues to study this aspect.

The RECOVERY trial is conducted by Oxford Population Health's registered clinical trials units in partnership with the Nuffield Department of Medicine. The trial is supported by a grant to the University of Oxford from UK Research and Innovation/the National Institute for Health Research (NIHR), as well as core funding from various sources including the Bill and Melinda Gates Foundation, the Foreign, Commonwealth & Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, NIHR Oxford Biomedical Research Centre, NIHR Clinical Trials Unit Support Funding, and Wellcome. Funding for RECOVERY outside the UK is provided by Wellcome through the COVID-19 Therapeutics Accelerator.

The RECOVERY trial is a large-scale effort that involves thousands of healthcare professionals, including doctors, nurses, pharmacists, and research administrators, across 178 hospitals throughout the UK. The trial is supported by various organizations and entities in the UK, including the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. This collaborative effort brings together expertise and resources from multiple sources to conduct the trial effectively.

*Note: this is a joint press release from the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and The Lancet.  Please credit both the congress and the journal in your stories*