Abstract
BackgroundAdministration of glucocorticoids might reduce mortality in patients with severe COVID-19 but have adverse cardiometabolic effects. Objectivesto investigate the effect of systemic administration of glucocorticoids on cardiovascular complications and all-cause mortality in patients hospitalised with respiratory viral infections, including COVID-19, SARS, MERS and influenza. MethodsWe identified randomised trials published prior to July 28th, 2021. The Mantel-Haenszel random effects method and the Hartung and Knapp adjustment were used to obtain pooled estimates of treatment effect with 95% confidence intervals. ResultsNo randomised trials of glucocorticoids for SARS, MERS or influenza reported relevant outcomes. We included eleven COVID-19 randomised trials (8109 patients). Overall, compared to placebo or standard care, glucocorticoids were not associated with a reduction of in-hospital mortality (p = 0.09). In a pre-specified sub-analysis, in-hospital mortality was reduced by 19% when follow-up was restricted to 14 days from randomisation (5/11 trials, 1329 patients, p = 0.02). With longer follow-up (9/11 trials, 7874 patients), administration of glucocorticoids was associated with a trend to benefit for those requiring mechanical ventilation (RR 0.86; 95% CI 0.57–1.27) but possible harm for those not receiving oxygen at randomisation (RR 1.27; 95% CI 1.00 – 1.61), an effect that was significantly different amongst subgroups (p = 0.0359). Glucocorticoids reduced the risk of worsening renal function by 37% (4/11 trials); reported rate of other cardiovascular complications was low. ConclusionsAdministration of systemic glucocorticoids to patients hospitalised with COVID-19 does not lower mortality overall but may reduce it in those requiring respiratory support and increase it in those who do not.
Highlights
Glucocorticoids are potent anti-inflammatory drugs that have been used, without much supporting evidence, as adjuvant therapy for viral pneumonias, including severe acute respiratory syndrome (SARS) [1], Middle East respiratory syndrome (MERS) [2] and influenza [3], but have been more widely studied in patients with COVID-19
With a survival benefit in patients hospitalised with COVID-19, especially amongst those requiring ventilation or oxygen therapy; these findings were supported by a meta-analysis that included an additional six trials, leading to dexamethasone rapidly being recommended in therapeutic protocols for patients with severe COVID-19 [5]
We systematically searched for pre-prints and published peer-reviewed studies in Medline (PubMed), Embase (Ovid), the Cochrane Central Reg ister of Controlled Trials (CENTRAL), and the Cochrane COVID-19 register to identify randomised trials that evaluated the use of glucocorticoids in patients with COVID-19, MERS, SARS and influenza
Summary
Glucocorticoids are potent anti-inflammatory drugs that have been used, without much supporting evidence, as adjuvant therapy for viral pneumonias, including severe acute respiratory syndrome (SARS) [1], Middle East respiratory syndrome (MERS) [2] and influenza [3], but have been more widely studied in patients with COVID-19. Administration of glucocorticoids might reduce mortality in patients with severe COVID-19 but have adverse cardiometabolic effects. Objectives: to investigate the effect of systemic administration of glucocorticoids on cardiovascular complications and all-cause mortality in patients hospitalised with respiratory viral infections, including COVID-19, SARS, MERS and influenza. With longer follow-up (9/11 trials, 7874 patients), administration of glucocorticoids was associated with a trend to benefit for those requiring mechanical ventilation (RR 0.86; 95% CI 0.57–1.27) but possible harm for those not receiving oxygen at randomisation (RR 1.27; 95% CI 1.00 – 1.61), an effect that was significantly different amongst subgroups (p = 0.0359). Conclusions: Administration of systemic glucocorticoids to patients hospitalised with COVID-19 does not lower mortality overall but may reduce it in those requiring respiratory support and increase it in those who do not
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