key: cord-1011753-5x7uvaoh
authors: Aucoin, Monique; Cooley, Kieran; Saunders, Paul Richard; Cardozo, Valentina; Remy, Daniella; Cramer, Holger; Abad, Carlos Neyre; Hannan, Nicole
title: The effect of quercetin on the prevention or treatment of COVID-19 and other respiratory tract infections in humans: a rapid review
date: 2020-07-30
journal: Adv Integr Med
DOI: 10.1016/j.aimed.2020.07.007
sha: 1c7a6d4478c7f99582a13207dcb4dc43aac4a02f
doc_id: 1011753
cord_uid: 5x7uvaoh

Brief overview There is currently insufficient evidence to recommend quercetin supplementation as a therapy for the treatment or prevention of COVID-19. Three human clinical trials with low risk of bias suggest that oral quercetin may have a beneficial effect on the incidence and duration of respiratory tract infections in certain populations; however, further research is needed. Verdict Current evidence on the efficacy of quercetin supplementation in the treatment and prevention of COVID-19 is insufficient for its clinical recommendation at this time. Quercetin exhibits both immunomodulatory and antimicrobial effects in preclinical studies; however, only three human clinical trials, each with a low risk of bias rating, were identified in this rapid review. One study reported a decrease in incidence of upper respiratory tract infections following a competitive athletic event. A larger community clinical trial reported a benefit in older, athletic adults only.

Quercetin is a polyphenolic compound, a type of flavonoid which is found in a variety of plants consumed by humans and available as a dietary supplement. Its physiologic effects include antioxidant, anti-inflammatory, immunomodulatory and anti-pathogenic properties (1) (2) (3) 

have demonstrated effects of quercetin on immune activity including increased neutrophil chemotaxis, macrophage phagocytosis, NK cell lytic activity and mitogen-stimulated lymphocyte proliferation.

Quercetin regulates the expression of some genes related to cytokine production (2) . When added to cell cultures, quercetin exerts antiviral and antibacterial properties, including inhibition of influenza A strains H1N1, H3N2 and inhibition of H5N1 entry (4) . Quercetin supplements are used by some naturopathic doctors to support healthy immune function and response to inflammation. Research has been undertaken using quercetin supplementation in the general population and in competitive athletes as it is established that intense and prolonged exercise is responsible for a transient decrease in immune function and increase in risk of infection (2) .

What is the role of quercetin in the treatment and recovery of COVID-19 and other respiratory tract infections? OR historical article/)) AND ((Quercetin or Quercetol or 3,3′,4′,5,7-pentahydroxylavone.af) AND ("avian J o u r n a l P r e -p r o o f influenza (H5N1)"/ or "influenza A (H1N1)"/ or Influenza A virus/ or influenza C/ or exp influenza/ or highly pathogenic avian influenza/ or Influenza B virus/ or highly pathogenic avian influenza virus/ or avian influenza virus/ or seasonal influenza/ or "Influenza A virus (H1N1)"/ or Asian influenza/ or swine influenza/ or influenza A/ or pandemic influenza/ or Influenza C virus/ or influenza B/ or avian influenza/ or Influenza virus or SARS or MERS or respir$ or Middle East Respiratory Syndrome Coronavirus or severe acute respiratory syndrome/) Screening Titles and abstract screening and full text screening were completed by one reviewer and checked for accuracy by a second reviewer. Similarly, data extraction was completed by a single reviewer and checked for accuracy by a second reviewer. Any discrepancies were resolved by consensus.

The risk of bias (RoB) of study findings was assessed using the revised Cochrane RoB tool for randomised trials (RoB 2) https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/current-version-of-rob-2?authuser=0.

The search identified 138 results, including 22 duplicates. 116 citations were screened. The citations were screened by title and abstract against the inclusion and exclusion criteria, and 112 citations were excluded. The full text of the remaining four articles were assessed for eligibility and one was excluded due to an incorrect intervention. The remaining three studies underwent extraction.

All three studies were double-blind, placebo-controlled randomized clinical trials and were conducted in outpatient settings in the World Health Organization (WHO) region of the Americas. Two of the studies involved participants who were trained athletes (1,2) (n=40 and n=39 respectively), while the third involved a diverse range of 1023 healthy and unhealthy individuals from the community (3). The studies involving athlete participants delivered the intervention for 3 weeks before and 2 weeks after a competitive athletic event in order to assess for the prevention of immune disturbance (blood and salivary immune markers) and respiratory tract infection (questionnaire).

The two studies assessing the impact on athletic-event-related immune perturbation assessed blood levels of immune components (1, 2) . All 3 studies assessed the incidence and duration of respiratory tract infections using a symptom survey or checklist. 

The two studies involving athletes assessed for the potential of quercetin to counter the immune perturbations that occurred as a result of participation in the competitive athletic event; however, no statistically significant difference was observed between the treatment and control groups with respect to natural killer cells, granulocyte respiratory burst activity, monocyte cell counts or salivary IgA output (1, 2) .

In one post-athletic event study, no statistically significant difference was found in the duration of illness, as measured by total post-race illness days (2) . In the other, a statistically significant decrease in the incidence of upper respiratory tract infection symptoms in the two-week period following the event was reported (3).

In the study that included a large community sample, no statistically significant difference was observed in the incidence, severity or duration of respiratory tract infection between the intervention and control group (3). However, a priori sub-group analysis revealed two statistically significant differences favouring oral quercetin. Subjects older than 40 years of age who self-rated in the top half of the population for fitness level experienced a 36% reduction in Upper Respiratory Tract Infection (URTI) severity and 31% reduction in total URTI sick days compared to placebo when taking the 1000mg per day dose. Of the two studies reporting statistically significant benefits, one used quercetin as a monotherapy and the other used it in combination with vitamin C and nicotinamide.

Based on the evidence identified in this rapid review, quercetin may be an effective intervention to decrease the frequency and duration of respiratory tract infections; however, more research is needed. 

Quercetin reduces illness but not immune perturbations after intensive exercise

Post-160-km race illness rates and decreases in granulocyte respiratory burst and salivary IgA output are not countered by quercetin ingestion. International journal of sports medicine

Quercetin supplementation and upper respiratory tract infection: A randomized community clinical trial. Pharmacological research

Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry. Viruses