Steroid therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials

Abstract

There is an urgent need for effective treatment modalities for coronavirus disease 2019 (COVID-19). Data for the use of steroids in COVID-19 is emerging. We conducted this systematic review and meta-analysis to estimate the effectiveness of steroid administration in mortality reduction due to COVID-19 compared to the control group. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of steroid therapy for COVID-19. An overall and subgroup (based upon the type of steroid) pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Six RCTs, including 7707 patients, were selected for review. Three trials reported 28-day mortality, and two trials reported 21-day mortality, and one trial reported in-hospital mortality. There were 730 deaths among 2837 participants in the steroid group while 1342 deaths among 4870 patients randomized to the control group (Odds ratio 0.76, 95% confidence interval 0.58-1.00, p=0.05). The effect was significant in patients on oxygen or mechanical ventilation. There was no difference in the various preparations and doses of the steroids. There was heterogeneity among the trials as the I2 value was 53%, with a p-value of 0.06. There was no indication of increased serious adverse events. This meta-analysis of RCTs demonstrated that the use of systemic corticosteroids is associated with a reduction in all-cause mortality in patients with COVID-19 on oxygen or mechanical ventilation.

Effect of glucocorticoids on the development of COVID‐19‐associated pulmonary aspergillosis: A meta‐analysis of 21 studies and 5174 patients

“…However, the RECOVERY trial demonstrated the impact of dexamethasone treatment on COVID‐19 overall mortality only but did not study its effect on the risk of developing secondary infections, including CAPA. Many clinical trials after the RECOVERY trial also reported the impact of GC on COVID‐19 mortality but with conflicting results, and there are limited data concerning the effect of GC on the risk of CAPA 51,52 . In addition to immunomodulation, 53 GC are also potent immunosuppressive agents, and they quantitatively and qualitatively affect cells of the innate and adaptive immune systems, making patients prone to developing secondary infections 14,15 .…”

“…Many clinical trials after the RECOVERY trial also reported the impact of GC on COVID-19 mortality but with conflicting results, and there are limited data concerning the effect of GC on the risk of CAPA. 51,52 In addition to immunomodulation, 53 GC are also potent immunosuppressive agents, and they quantitatively and qualitatively affect cells of the innate and adaptive immune systems, making patients prone to developing secondary infections. 14,15 In patients with COVID-19, who are inherently immunocompromised and have defective antifungal immunity, 48 GC treatment may further impair antifungal immunity and thereby increase susceptibility to developing CAPA.…”

Untitled

“…Boppana [37] 6 LOS was similar among pts receiving low-dose steroids, and those receiving high-dose steroids Footnotes. RCT, randomized clinical trial; SARS, severe acute respiratory syndrome; MERS, Middle East respiratory syndrome; pts, patients; OR, odds ratio; RR, risk ratio; RD, risk difference; HR, hazard ratio; ROB, Risk of bias; SOC, standard of care.…”

“…The tool is suitable for reviews including randomised and non-randomised studies. It includes 16 domains (7 considered critical) relating to the research question, review design, search strategy, study selection, data extraction, justification for excluded stud- Lee, 2020 [13] Li, 2020 [14] Yang, 2020 [15] Cantini, 2020 [16] Cheng, 2020 [17] Wang, 2020 [18] Sarma, 2020 [19] Tlayjeh, 2020 [20] WHO REACT Working Group, 2020 [21] Ye, 2020 [22] Van Paassen, 2020 [23] Chaudhuri, 2021 [24] Hasan, 2021 [25] Ma, 2021 [26] Pasin, 2021 [27] Pulakurthi, 2021 [28] Sahu, 2021 [29] Tu, 2021 [30] Cano, 2021 [31] Moosazadeh, 2021 [32] Nguyen, 2021 [33] Ferreto, 2021 [34] Yu, 2021 [35] Sahilu, 2021 [36] Boppana, 2021 [37] Wagner, 2021 [38] ies, description of included studies, risk of bias, sources of funding, meta-analysis, heterogeneity, publication bias, and conflicts of interest (see Table 2 for details of each question). Two review authors (MC, IP) independently assessed the quality of evidence in the included reviews and the methodological quality of the SRs.…”

The State-of-the-Art of Gene Editing and its Application to Viral Infections and Diseases Including COVID-19

“…Furthermore, a metanalysis of other RCTs declared that using systemic corticosteroids (prominent anti-inflammatory drugs) resulted in a decline in the mortality rate in ICU ill COVID-19 patients ( Boppana et al., 2021 ). For COVID-19 patients with stable conditions, adding Mefenamic acid (non-steroidal anti-inflammatory) to the standard care regimen on ambulatory COVID-19 patients was associated with a significant reduction in symptoms and shortage of the recovery period in comparison to the control group.…”