A systematic review on the effects of Echinacea supplementation on cytokine levels: Is there a role in COVID-19?

Abstract

COVID-19 is the respiratory illness caused by the novel coronavirus, SARS-CoV-2. Cytokine storm appears to be a factor in COVID-19 mortality. Echinacea species have been used historically for immune modulation. A previous rapid review suggested that Echinacea supplementation may decrease the levels of pro-inflammatory cytokines involved in cytokine storm. The objective of the present systematic review was to identify all research that has assessed changes in levels of cytokines relevant to cytokine storm in response to administration of Echinacea supplementation. The following databases were searched: Medline (Ovid), AMED (Ovid), CINAHL (EBSCO), EMBASE (Ovid). Title and abstract screening, full text screening, and data extraction were completed in duplicate using a piloted extraction template. Risk of bias assessment was completed. Qualitative analysis was used to assess for trends in cytokine level changes. The search identified 279 unique publications. After full text screening, 105 studies met criteria for inclusion including 13 human studies, 24 animal studies, and 71 in vitro or ex vivo studies. The data suggest that Echinacea supplementation may be associated with a decrease in the pro-inflammatory cytokines IL-6, IL-8, and TNF, as well as an increase in the anti-inflammatory cytokine IL-10. The risk of bias in the included studies was generally high. While there is currently no substantive research on the therapeutic effects of Echinacea in the management of either cytokine storm or COVID-19, the present evidence related to the herb's impact on cytokine levels suggests that further research may be warranted in the form of a clinical trial involving patients with COVID-19.

Keywords: ARDS, acute respiratory distress syndrome; CCL, C–C motif ligand chemokine; COVID-19; COVID-19, coronavirus disease 2019; CSF, Colony-stimulating factor; Cytokine; Cytokine release syndrome; Cytokine storm; Echinacea; GM-CSF, granulocyte-macrophage colony-stimulating factor; Herbal medicine; IFN, interferon; IL, interleukin; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; SARS, Severe acute respiratory syndrome; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TFN, tumor necrosis factor.

Fig. 1

PRISMA flow diagram of included studies.

Fig. 2

Change in cytokine levels following Echinacea exposure. A: Human studies, B: animal Studies, C: Cell culture studies.

Fig. 3

Risk of Bias 2.0 for human randomized controlled trials.

Fig. 4

ROBINS-I Assessment of bias for non-randomized human studies with a comparison.