Early Versus Late Use of Dexamethasone in Critically Ill Patients With COVID-19: A Multicenter, Prospective Cohort Study

Abstract

Background: Corticosteroids, especially dexamethasone, showed a survival benefit in critically ill COVID 19 patients. However, it is unclear whether the timing of dexamethasone initiation is associated with positive outcomes. The aim of this study is to evaluate the timing of dexamethasone initiation and 30-day ICU mortality in critically ill patients with COVID19. Methods: A multicenter, non-interventional, prospective study for all adult COVID19 admitted to intensive care units (ICUs) who received systemic dexamethasone between March 01 to December 31, 2020. Patients were divided into two groups based on the timing for dexamethasone initiation (early vs. late). Early use defined as the initiation of dexamethasone within three days of ICU admission. Multivariate logistic and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. Results: A total of 475 patients were included in the study; dexamethasone was initiated early within three days of ICU admission in 433 patients. Early initiation of dexamethasone was associated with lower 30-day ICU mortality (OR [95%CI]: 0.43 [0.23, 0.81], p-value = 0.01), and acute kidney injury during ICU stay, (OR [95%CI]: 0.45 [0.21, 0.94], p-value = 0.03). Additionally, among survivors, early initiation was associated with shorter MV duration (beta coefficient [95% CI]: -0.94 [-1.477, -0.395], p-value = 0.0001), ICU length of stay (LOS) (beta coefficient [95%CI]: -0.73 [-0.9971, -0.469], p-value = 0.0001), and hospital LOS (beta coefficient [95%CI]: -0.68 [-0.913, -0.452], p-value = 0.0001). Conclusion: Early initiation of dexamethasone within three days of ICU admission in COVID-19 critically ill patients was associated with a mortality benefit. Additionally, it was associated with shorter MV duration, hospital, and ICU LOS.

The Impact of ACE2 Polymorphisms on COVID-19 Disease: Susceptibility, Severity, and Therapy

“…Therefore, it is reasonable to assume ACE2 variant rs2106809 T allele or some other SNPs in the same linkage disequilibrium block, may be functional and could decrease the sACE2 expression and increase the susceptibility to hypertension. Considering the double effect of sACE2 on hypertension and antiviral activity, this may partly explain the high incidence rate of hypertension (58%) in critically ill patients with COVID-19 (Sulaiman et al, 2021). By the way, ACE2 rs2074192 T allele and rs2285666 G allele, which are listed in the Table 2, have been reported to be associated with more severe clinical outcomes of SARS-CoV-2 infection (Cafiero et al, 2021;Mohlendick et al, 2021).…”

Potential Adverse Effects of Dexamethasone Therapy on COVID-19 Patients: Review and Recommendations

“…However, many researchers pointed out that, in practice, the symptom onset is usually impossible to ascertain, and the signs of severity often appear late. In a study that assessed the association between the dexamethasone initiation time and mortality benefits, Sulaiman et al (2021) found survival benefits with the early initiation in critically ill COVID-19 patients [26]. The WHO panel concluded that it is preferable that critical COVID-19 patients receive corticosteroids (even if within 7 days of symptom onset) but noncritical patients do not (even if after 7 days of symptoms onset) [27].…”