The association of sickle cell disorder with adverse outcomes in COVID‐19 patients: A meta‐analysis

Abstract

The aim is to elucidate the relationship between sickle cell disorder and severe COVID‐19. We systematically searched the required articles in three electronic databases, extracting and pooling effect sizes (ES) and 95% confidence interval (CI) from each eligible study to evaluate the effect of combined sickle cell disorder on adverse consequences in patients with COVID‐19. This meta‐analysis included 21 studies. Sickle cell disease (SCD) was a risk factor for mortality (pooled ES = 1.70, 95% CI: 1.00–2.92, p = 0.001), hospitalization (pooled ES = 6.21, 95% CI: 3.60–10.70, p = 0.000) and intensive care unit (ICU) admission (pooled ES = 2.29, 95% CI: 1.61–3.24, p = 0.099) in COVID‐19 patients. Patients with SCD had an increased risk of respiratory failure/mechanical ventilation, but a statistical association was not found (pooled ES = 1.21, 95%CI: 0.74‐1.98, p = 0.036). There was significant heterogeneity between SCD and death, hospitalization, and respiratory failure/mechanical ventilation. The results of meta‐regression of SCD and hospitalization suggested that the tested variables including Area (p = 0.642), study design (p = 0.739), sample size (p = 0.397), proportion of males (p = 0.708), effect type (p = 0.723), whether confounding factors are adjusted (p = 0.606) might not be the source of heterogeneity. In addition, sickle cell trait (SCT) was significantly associated with the mortality (pooled ES = 1.54, 95% CI: 1.28–1.85, p = 0.771) and hospitalization (pooled ES = 1.20, 95% CI: 1.07–1.35，p = 0.519) in patients with COVID‐19. But any increased risk of ICU admission/severe (pooled ES = 1.24, 95% CI: 0.95–1.62, p = 0.520) and mechanical ventilation (OR = 1.00, 95%CI:0.59‐1.69) in COVID‐19 patients with SCT was not observed. Sensitivity analysis demonstrated that the results were robust. The results of the funnel plot and Egger's test did not support the existence of publication bias. Current meta‐analysis indicated that sickle cell disorder has a meaningful impact on COVID‐19 progression to severe cases and associated deaths. However, further investigations and research to validate the current findings is indispensable.

Comment on “The association of sickle cell disorder with adverse outcomes in COVID‐19 patients: A meta‐analysis”

“…The analysis by Liang et al 1 provided evidence that patients with SCD are particularly vulnerable during the pandemic. The authors should be congratulated for their efforts to characterize the risk and fill the knowledge gaps around COVID-19 and SCD.However, we wish to emphasize a significant issue that could enhance the comprehensiveness of the study by Liang et al 1 The authors found that SCD significantly increased the risk of hospitalization (pooled odds ratio: 6.21) compared with other outcomes such as mortality (pooled odds ratio: 1.7) and intensive care unit (ICU) admission (pooled odds ratio: 2.29). 1 This highlights that hospitaliza-…”

“…However, we wish to emphasize a significant issue that could enhance the comprehensiveness of the study by Liang et al 1 The authors found that SCD significantly increased the risk of hospitalization (pooled odds ratio: 6.21) compared with other outcomes such as mortality (pooled odds ratio: 1.7) and intensive care unit (ICU) admission (pooled odds ratio: 2.29). 1 This highlights that hospitaliza-…”

“…We propose that patient age could be a contributing factor given the inclusion of various age groups (i.e., children, adolescents, and adults) in the original meta-analysis. 1 To investigate this, we conducted an additional subgroup analysis, splitting the studies into adults (≥18 years old), mixed-age populations (including both children/adolescents and adults), and children/ adolescents (<18 years old). The raw data in the original metaanalysis 1 were analyzed using the Cochrane Review Manager (RevMan 5.3; Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2014).…”

“…1 To investigate this, we conducted an additional subgroup analysis, splitting the studies into adults (≥18 years old), mixed-age populations (including both children/adolescents and adults), and children/ adolescents (<18 years old). The raw data in the original metaanalysis 1 were analyzed using the Cochrane Review Manager (RevMan 5.3; Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2014). As shown in Figure 1, heterogeneity was reduced within all subgroups, suggesting that age may be another contributing factor to heterogeneity.…”