Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial.

BACKGROUND: Corticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS and thereby reduce death. METHODS/DESIGN: This is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission but are at risk factors for the development of ARDS. Risk for the development of ARDS is defined as levels of lactate dehydrogenase > 245 U/L, C-reactive protein > 100 mg/L, and lymphocyte count of < 0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive a dose of 6 mg once daily during 7 days. The primary outcome is a composite of the development of moderate or more severe ARDS and all-cause mortality during the 30-day period following enrolment. DISCUSSION: If our hypothesis is correct, the results of this study will provide additional insights into the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Impact of Systemic Corticosteroids on Mortality in Older Adults With Critical COVID-19 Pneumonia.

BACKGROUND: The most susceptible population group to critical and fatal coronavirus disease 2019 (COVID-19) is older adults. In severe acute respiratory syndrome coronavirus 2 infection, the host immune response is thought to play a key role in the pathophysiological effects of lung damage. Therefore, corticosteroid therapy could modulate inflammation-mediated pulmonary injury and thereby reduce progression to severe respiratory failure and death. The aim of this study was to analyze the safety and clinical efficacy of corticosteroid therapy in older adults with severe COVID-19 pneumonia. METHOD: We reviewed the clinical records of confirmed COVID-19 patients aged 75 years or older admitted to our hospital over a 3-month period (March 1-May 31, 2020). A total of 143 patients were included in the study cohort. From 2 April, 2020, in accordance with World Health Organization guidance on COVID-19, our hospital protocol added corticosteroid for COVID-19 treatment. We compared in-hospital mortality among patients with critical COVID-19 who received corticosteroids therapy and those who did not. RESULTS: In total, 88 patients (61.5%) were treated with corticosteroids, and 55 patients (38.4%) were not. Both groups were similar in baseline characteristics. The median age was 85 years (interquartile range: 82-89), and 61.5% (88/143) were male. In-hospital mortality was lower in the corticosteroid group (68.2%) compared with patients in the noncorticosteroid group (81.8%). Treatment with corticosteroids was an independent survival factor (hazard ratio: 0.61; 95% CI: 0.41-0.93; p = .006). CONCLUSIONS: In critically ill older adults with COVID-19 pneumonia, the use of corticosteroid treatment resulted in lower mortality without severe adverse events.