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

Monique Aucoin,Valentina Cardozo,Meagan D Mclaren,Anna Garber,Daniella Remy,Joy Baker,Adam Gratton,Mohammed Ali Kala,Sasha Monteiro,Cara Warder,Alessandra Perciballi,Kieran Cooley

doi:10.1016/j.metop.2021.100115

Monique Aucoin, Valentina Cardozo + Show 10 more

Open Access

https://doi.org/10.1016/j.metop.2021.100115

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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.

Highlights

Journal Pre-proof In early January of 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the agent responsible for coronavirus disease 2019 (COVID-19)(1)
A recent literature review proposed a unified characterization of cytokine storm based on three criteria: “elevated cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction beyond that which could be attributed to a normal response to a pathogen, if a pathogen is present''(7)
The second most commonly studied species was E. angustifolia; with approximately 8% of studies using it on its own and 18% using it in combination with other species

Summary

Introduction

Journal Pre-proof In early January of 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the agent responsible for coronavirus disease 2019 (COVID-19)(1). When considering the role of cytokines in COVID-19 it has been observed that higher levels of IL-6, IL-8 and TNF, at the time of admission, were associated with significantly lower rates of survival after adjusting for demographics and comorbidities as confounding variables.[8] An association between higher IL-6 and IL-8 levels and increasing disease severity was observed[8]. In another cohort of COVID-19 patients, highly impaired Interferon (IFN) type 1 response was consistent among severe and critically ill patients.[9] Decreased levels of INF-α and IFN-β were associated with ongoing elevation in blood viral load and an over-active response of proinflammatory modulators TNF and IL-6(9)

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