This article is part of our May 2023 Immune Health special issue. Download the full issue here.
Reference
Di Pierro F, Kham A, Iqtadar S, et al. Quercetin as a possible complementary agent for early-stage COVID-19: concluding results of a randomized clinical trial. Front Pharmacol. 2023;13:1096853.
Study Objective
To assess possible therapeutic effects of quercetin in outpatients with early-stage, mild-to-moderate symptoms of Covid-19.
Key Takeaway
In this study, patients taking quercetin during early-stage Covid cleared the virus and experienced symptom resolution significantly earlier than those in a control group.
Design
Open-label, randomized, controlled clinical trial.
Participants
There were 108 participants who started the trial and were randomly assigned in a 1:1 ratio to a treatment or control group. There were 4 participants per group who dropped out, leaving a total of 50 participants per group (50% female in the control group; 54% female in the quercetin group). A significant difference between the groups was that the treatment group had a mean age of 41.1 years and the control group had a mean age of 54.1 years.
Inclusion criteria included being 18 years or older, positive RT-PCR (reverse transcription–polymerase chain reaction) test results, and mild-moderate Covid-19 symptoms defined as: fever, dyspnea, dry cough, sore throat, myalgia, and/or weakness. In addition, participants had to have an O2 stat over 93% and be appropriate candidates for outpatient care.
Exclusion criteria included allergy to quercetin, chronic kidney disease, pregnancy, severe hypotension, moderate-to-severe thrombocytopenia, and being on an immune stimulant prior to time of enrollment.
Comorbidities and symptom profile between groups were well-matched. This trial took place in Lahore, Pakistan. The paper made no mention of racial identity. Notably, none of the participants were vaccinated.
Intervention
Participants received 500 mg quercetin phytosome 3 times daily for 1 week and 2 times daily for week 2 as an add-on to standardized care. The control group received only standardized care; no placebo was used.
Study Parameters Assessed
This study measured SARS-CoV-2 infection by RT-PCR testing and symptom prevalence and severity as clinically assessed by outpatient physicians. Additionally, investigators assessed laboratory levels of C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), ferritin, and complete blood count (CBC).
Primary Outcome
The primary outcomes assessed in this study were the time needed to achieve a negative SARS-CoV-2 RT-PCR test and improvement in acute symptoms at the 1- and 2-week mark as assessed by an outpatient physician. Secondary outcomes included laboratory changes over the same period.
Key Findings
The quercetin treatment group had significantly more participants test negative for the SARS-CoV-2 virus at 1 week compared to the control group (68% vs 24%, P=0.0004). Interestingly, by week 2 nearly all participants, regardless of group, had cleared the virus (98% in treatment group and 94% in control).
Clinical resolution of acute symptoms also occurred more quickly in the treatment group (52%) vs the control (24%; P=0.0031). Again, both groups seemed to fare equally well at the 2-week mark, with “most of patients” being free of symptoms—although the article did not show this specific dataset.
Transparency
The quercetin phytosome used in this trial was donated by 2 companies (PharmExtracta and Indena) that distribute the quercetin phytosome; 4 of the 13 authors are on the boards of said companies.
Practice Implications & Limitations
As we are learning to coexist with SARS-CoV-2, any information on how to mitigate the impact and improve patient outcomes is welcome. The most compelling component of this study from a clinical standpoint was the accessibility of the intervention: The quercetin phytosome was dosed at 500 mg 3 times a day for the first week and 500 mg 2 times a day for the subsequent week. Additionally, participants tolerated the intervention well, with no adverse effects reported.
However, the study has some significant limitations. The first is the significant age difference between the treatment group (mean age 41.1 years) and the control group (mean age 54.1 years). With age being one of the main risk factors for acute complications from SARS-CoV-2 infection, it is hard to know if we can attribute the benefits seen in the treatment group to quercetin or just younger age. The small sample size is also a drawback—although one that is common in the evaluation of complementary treatments. Additionally, we can only hypothesize how these findings may translate into a vaccinated population.
Despite these limitations, the outcomes at 1 week are impressive; certainly many of our patients would love to clear the virus more quickly and, thus, decrease the timeframe in which they could possibly infect others. Moreover, many patients would be quite thrilled with any intervention that reduces their acute symptomatic phase. With these 2 things in mind, I think many clinicians might be willing to offer this safe, relatively inexpensive, and possibly beneficial intervention.
Another compelling finding was the similarity between the 2 groups after 2 weeks. At this point, nearly all patients had cleared the virus and were asymptomatic. Put another way, while the phytosomal quercetin seemed to speed recovery, both groups eventually recovered by the end of 2 weeks. This rapid recovery may have been in part due to the mean age of both groups, their outpatient status, and (possibly) their lack of comorbidities (though the article did not clearly define these).
Fortunately, most people who contract Covid will recover. The odds greatly increase with lower age and lack of complicating health factors. The statistics vary around what percentage of these patients go on to develop symptoms of long Covid, and certainly we could use more clarity about the definition and prevalence of this syndrome. It would be interesting to note if the quercetin intervention affected the development of long-Covid symptoms, though the small sample size would likely preclude any statistically significant data.
Nevertheless, phytosomal quercetin may be an accessible and safe option to offer patients looking to shorten their symptomatic Covid, even though clearance is the most likely natural course of the infection.
