Higher-dose corticosteroids are linked to a 60% increased risk of death in hospitalized COVID-19 patients with low oxygen levels, finds a randomized, controlled trial published yesterday in The Lancet.

The study will also be presented at the April 15 to 18 European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen, Denmark.

For the open-label platform trial, RECOVERY Collaborative Group researchers evaluated the outcomes of 1,272 adult COVID-19 patients receiving no oxygen and 1,264 receiving noninvasive oxygen in Asia, Africa, and the United Kingdom from May 25, 2021, to May 13, 2022. Recruitment of these patients stopped on May 11 for safety reasons.

The patients were randomly assigned to receive high-dose corticosteroids (659 patients) or standard care (613; 87% received low-dose corticosteroids). The high-dose regimen consisted of 20 milligrams (mg) dexamethasone once daily for 5 days followed by 10 mg for 5 days, while the low-dose regimen included 6 mg once daily for 10 days. Of all patients, 19% had diabetes, and 60% were men.

The authors had already shown that low-dose corticosteroids reduce deaths among COVID-19 patients needing supplemental oxygen.

Higher rates of pneumonia, hyperglycemia

Among the 659 high-dose recipients, 123 (19%) died, compared with 75 of 613 (12%) usual-care patients, a 59% difference. The high-dose group also had more non-COVID pneumonia than usual-care patients (10% vs 6%; absolute difference, 3.7%) and hyperglycemia requiring more insulin (22% vs 14%; absolute difference, 7.4%).

The researchers continue to study whether a higher corticosteroid dose benefits patients requiring ventilation.

In a related commentary, Anders Perner, MD, PhD, of Copenhagen University Hospital, and Balasubramanian Venkatesh, MD, of Australia's University of New South Wales, said that evolving SARS-CoV-2 variants and increased vaccination rates complicate prediction of the use of anti-inflammatory strategies in these patients.

"We will be better informed when the results of the subgroup of patients on ventilation or ECMO [extracorporeal membrane oxygenation] in the RECOVERY trial become available and when all trials of higher-dose versus standard-dose dexamethasone in patients with COVID-19 and hypoxaemia have undergone meta-analysis," they wrote.

The University of Oxford announced today that Ghana has become the first country in the world to approve the malaria vaccine that it developed, R21/Matrix-M, which is licensed and made by the Serum Institute of India (SII).

Regulatory officials in Ghana approved the vaccine for use in children ages 5 to 36 months, the group at highest risk of death from malaria. The vaccine, which contains the Novavax Matrix-M adjuvant (immune-booster), is given in three doses.

The clearance was based on efficacy and safety results from phase 2 trials, including one that suggests an extra booster dose given 1 year after the primary series maintained high efficacy and meets the World Health Organization malaria vaccine roadmap goal of providing efficacy of at least 75%. The trials took place in the United Kingdom, Thailand, and several African countries.

A phase 3 trial that enrolled about 4,800 children is still under way, with results expected later this year.

SII said it has the capacity to make more than 200 million doses a year. Oxford said in its statement that the low-dose vaccine can be made at mass scale at moderate cost, which could help ease the significant burden of malaria in African countries.