Dosage and utilization of dexamethasone in the management of COVID-19: A critical review.

Abstract

Background: The severe respiratory manifestations observed in severe coronavirus disease 2019 (COVID-19) cases are often associated with an excessive inflammatory response. Dexamethasone, a synthetic glucocorticoid, exerts its anti-inflammatory effects by inhibiting the transcription of pro-inflammatory genes and suppressing the activity of various immune cells. This mechanism has implications for mitigating the cytokine storm observed in severe COVID-19 cases. Early on in the pandemic, the Recovery Collaborative working group showed a mortality benefit of using dexamethasone in decreasing mortality in patients with COVID-19 requiring respiratory support. However, the optimal dosage of corticosteroids remains debatable. Several studies that compare different doses of dexamethasone in COVID-19 exist, but the results are conflicting.

Aim: To review the latest evidence regarding dosage, safety, and efficacy of dexamethasone in severe COVID-19.

Methods: We followed preferred reporting items for systematic reviews and meta-analysis guidelines. A detailed literature search was conducted across PubMed, Google Scholar, and Medline to include publications up to March 2024. Our keywords included "COVID-19" "SARS-CoV-2" "dexamethasone" "corticosteroid" "steroid" and "glucocorticoid"-along with their combinations. We employed the Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale to evaluate the integrity and potential of bias in the included studies. A meta-analysis was conducted using a random-effects model, assessing pooled odds ratios and mean differences, with heterogeneity gauged by the I ² statistic and the χ ² tests.

Results: No statistical differences were found in 28-day all-cause mortality [pooled odds ratio (OR) = 1.109, 95%CI: 0.918-1.340], 60-day all-cause mortality (OR = 0.873, 95%CI: 0.744-1.024; I ² = 47.29%), mean length of hospital stay (mean difference = -0.08 days, 95%CI: -0.001 to 0.161) and adverse events (OR = 0.877, 95%CI: 0.707-1.087).

Conclusion: Differing doses of corticosteroids have no clinical implications on mortality, mean length of hospital stay, and adverse events in COVID-19 patients. Additional research is required in patients requiring invasive or non-invasive ventilation.