COVID-19 preprint data led to ‘immediate, dramatic change’ in critical care practice

ByErin T. Welsh, MA

Preprint data on the use of dexamethasone influenced clinical practice in treating patients with COVID-19 in Australia, researchers reported.

Researchers aimed to examine the impact of preprint data — scientific papers that are posted online rapidly before peer review — on the management of critically ill patients with COVID-19. Preprint services have been increasingly used by researchers since the beginning of the COVID-19 pandemic to disseminate findings quickly and prior to peer-review publication, according to a press release issued by the American Thoracic Society.

Corticosteroid use in patient with COVID-19 before and after preprint release of the RECOVERY trial.

“We were interested to quantify the impact of the RECOVERY trial findings on clinical practice in ICUs in Australia, so as to assess the speed and extend of uptake of corticosteroid therapy,” Andrew A. Udy, PhD, professor of critical care research in the Australian and New Zealand Intensive Care Research Centre in the School of Public Health and Preventive Medicine at Monash University and clinician and researcher in the department of intensive care and hyperbaric medicine at The Alfred Hospital, Melbourne, told Healio. “Our data confirm rapid, wholesale implementation of this treatment. It is interesting to contrast this with the ‘typical’ time frame over which clinical trial results are translated into clinical practice, which is often many years.”

As Healio previously reported, the RECOVERY trial evaluated the corticosteroid dexamethasone in patients hospitalized with clinically suspected or confirmed SARS-CoV-2 infection. Results demonstrated a reduction in 28-day mortality in patients receiving mechanical ventilation or oxygen supplementation. Preprint results from the RECOVERY trial were released in the preprint server for health sciences, medRxiv, June. The final paper was published in The New England Journal of Medicine in July without any major changes.

Udy and colleagues analyzed SPRINT-SARI, a multicenter, prospective, observational database of all patients with laboratory-confirmed COVID-19 admitted to 53 ICUs in Australia from Feb. 27 to Nov. 11. The researchers compared corticosteroid use in 461 adults (mean age, 61 years; 64% men) before preprint release, after preprint release and after formal publication.

Mechanical ventilation was used in 37% of patients on the first day of hospitalization and in 55.3% at any point during the ICU stay. Overall in-hospital mortality was 13.2%, according to the study.

Researchers observed an increase in corticosteroid use over time: 29.5% of patients were receiving corticosteroids before preprint release compared with 92% of patients after preprint release (absolute difference, 62.5 percentage points; 95% CI, 51.3-73.6; P < .001). Use increased to 95.8% of patients after formal publication of results from the RECOVERY trial (absolute difference, 3.8 percentage points; 95% CI, –5.4% to 13.1%; P = .275).

“[P]reprint release of the RECOVERY trial findings led to an almost immediate, dramatic change in corticosteroid use in critically ill COVID-19 patients across Australia,” the researchers wrote in the letter published in the American Journal of Respiratory and Critical Care Medicine. Corticosteroid use also increased after preprint release in patients requiring no respiratory support (from 4% to 66.7%), patients requiring low-flow oxygen (from 7.7% to 100%), patients requiring high-flow nasal cannula or noninvasive ventilation (from 35.9% to 100%) and patients requiring mechanical ventilation (from 48.6% to 93.1%).

The researchers reported an increase in corticosteroid use in ICUs with 10 or fewer beds (from 45.2% to 95.8%), 11 to 20 beds (from 28.9% to 88.9%) and more than 20 beds (from 25.8% to 96.4%) after the preprint release.

Before the results of the RECOVERY trial, the Australian and New Zealand Intensive Care Society recommended against corticosteroid use in COVID-19 guidelines.

“This highlights the potential impact of preprint services, in terms of immediate clinical translation,” Udy told Healio. “Whether this applies to all preprint publications is, of course, debatable and our findings likely reflect the current climate — that of a global, viral pandemic — the appetite of clinicians to provide some form of disease-modifying treatment and the very high-quality nature of the RECOVERY trial.”