Efficacy of Supplemental Hemoadsorption Therapy on Severe and Critical Patients With Covid-19: An Evidence-Based Analysis

Abstract

Background The COVID-19 pandemic has posed a disproportionately high threat to the global health system and social stability. COVID-19 damage can lead to hyperinflammation and tissue damage due to a "cytokine storm", which in turn contributes to an increase in the mortality rate. Extracorporeal hemoadsorption therapy (HAT) in patients with severe COVID-19 may improve organ function and stabilize hemodynamic status; however, the effects of supplemental HAT remain controversial. Methods The Cochrane Library, Embase and PubMed databases were comprehensively searched from inception to August 20, 2022 for potential studies. Results A total of 648 patients with severe COVID-19 in 3 randomized controlled trials and 11 observational studies met the inclusion criteria. A meta-analysis indicated that supplemental HAT significantly improved the mortality rate of patients with severe COVID-19 compared with conventional therapy (CT) (RR = 0.74, 95% CI: [0.56, 0.96], P = 0.026). In subgroup analyses, supplemental HAT significantly decreased mortality rates in patients without extracorporeal membrane oxygenation (ECMO) support (RR = 0.59, 95% CI: [0.44, 0.79], P < 0.0001), while a significant difference was not observed in patients requiring ECMO support (RR = 1.61, 95% CI: [0.63, 4.09], P = 0.316). Standardized mean difference (SMD) meta-analysis showed that IL-6 removal was more significant in HAT group than CT group (SMD = 0.46, 95% CI: [0.01, 0.91], P = 0.043), followed by CRP (SMD = 0.70, 95% CI: [-0.04, 1.44], P = 0.065) and IL-8 (SMD = 0.36, 95% CI: [-0.34, 1.07], P = 0.311). No evidence of substantial publication bias concerning mortality was observed. Conclusion Given the better mortality outcomes, HAT confers clinical benefits to patients with severe COVID-19, which correlated with cytokine removal by HAT. Cytokine adsorption may not provide clinical benefits for patients with severe COVID-19 requiring ECMO and should be used with caution. However, due to the very low quality of evidence, multicenter randomized trials with large sample sizes are required to verify these findings.

Higher levels of IL-1ra, IL-6, IL-8, MCP-1, MIP-3α, MIP-3β, and fractalkine are associated with 90-day mortality in 132 non-immunomodulated hospitalized patients with COVID-19

“…This indicates that many molecules can function as drug targets in COVID-19 associated cytokine storm if they are part of central inflammatory pathways. Reducing the general levels of circulating cytokines through hemoadsorption, remains more controversial, as some studies report a decrease in mortality, while others have found no improvement or even negative effects on survival [ 40 , 41 ].…”

Evidence from fatal COVID-19 for targeting the bradykinin metabolism - a single-center cohort study

“…In particular, initial mutants of the virus cause severe COVID-19, and infected patients admitted to the intensive care unit (ICU) usually first present with pneumonitis combined with increased oxygen demand, often leading to acute respiratory distress syndrome (ARDS) and multiple additional symptoms, for example, vasculitis or renal failure, frequently linked to increased inflammation. Addressing the inflammatory processes has become an elementary therapeutic concept but is not highly specific (2)(3)(4)(5). It has been postulated that inflammatory symptoms can be linked to a dysregulated kinin-kallikrein-system (KKS) and renin-angiotensin-aldesterone system (RAAS), leading to a "bradykinin storm" in multiple tissues and systems, resulting finally in observed COVID-ARDS and multiple organ failure (6)(7)(8)(9)(10).…”