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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: final results of a randomized clinical trial.Front Pharmacol. 2023;13:1096853.
Study objective
To assess possible therapeutic effects of quercetin in outpatients with mild to moderate symptoms of early-stage Covid-19.
Key to take away
In this study, patients who took quercetin in the early stages of Covid cleared the virus and experienced significantly earlier improvement in symptoms than those in a control group.
design
Open, randomized, controlled clinical trial.
Participant
There were 108 participants who began the study and were randomly assigned to a treatment or control group in a 1:1 ratio. There were 4 participants per group who dropped out, leaving a total of 50 participants per group (50% women in the control group; 54% women 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 a minimum age of 18 years, positive reverse transcription-polymerase chain reaction (RT-PCR) test results, and mild to moderate Covid-19 symptoms defined as: fever, shortness of breath, dry cough, sore throat, myalgia, and/or weakness. In addition, participants had to have an O2stat over 93% and be suitable candidates for outpatient care.
Exclusion criteria included allergy to quercetin, chronic kidney disease, pregnancy, severe hypotension, moderate to severe thrombocytopenia, and use of an immunostimulant before the time of enrollment.
Comorbidities and symptom profiles between groups were well matched. This trial took place in Lahore, Pakistan. There was no mention of racial identity in the newspaper. Notably, none of the participants were vaccinated.
intervention
Participants received quercetin phytosome 500 mg three times daily and twice daily for 1 week as an adjunct to standard care. The control group received only standardized care; No placebo was used.
Evaluated study parameters
This study measured SARS-CoV-2 infection using RT-PCR testing and the prevalence and severity of symptoms as clinically assessed by outpatient physicians. In addition, researchers assessed laboratory values of C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin and a complete blood count (CBC).
Primary outcome
The primary outcomes assessed in this study were time required to achieve a negative SARS-CoV-2 RT-PCR test and improvement in acute symptoms at 1 and 2 weeks, as assessed by an outpatient clinician. Secondary outcomes included laboratory changes during the same period.
Key findings
In the quercetin treatment group, there were significantly more participants who tested negative for the SARS-CoV-2 virus after one week compared to the control group (68% vs. 24%).P=0.0004). Interestingly, by week 2, almost all participants, regardless of group, had cleared the virus (98% in the treatment group and 94% in the control group).
The clinical resolution of acute symptoms was also faster in the treatment group (52%) than in the control group (24%;P=0.0031). Again, both groups appeared to be doing equally well after two weeks, with “most patients” free of symptoms – although the article did not include that specific data set.
transparency
The quercetin phytosome used in this experiment was donated by two companies (PharmExtracta and Indena) that distribute the quercetin phytosome; 4 of the 13 authors sit on the boards of the companies mentioned.
Implications and limitations for practice
As we learn to coexist with SARS-CoV-2, any information on how we can mitigate its impact and improve patient outcomes is welcome. From a clinical perspective, the most compelling component of this study was the accessibility of the intervention: the quercetin phytosome was dosed at 500 mg three times daily in the first week and 500 mg twice daily in the following week. Furthermore, participants tolerated the intervention well, with no side 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). Since age is one of the main risk factors for acute complications of SARS-CoV-2 infection, it is difficult to say whether we can attribute the benefits observed in the treatment group to quercetin or just to younger age. The small sample size is also a disadvantage – although a common disadvantage when evaluating complementary treatments. Furthermore, we can only guess at how these results translate to a vaccinated population.
Despite these limitations, the results after one week are impressive; Certainly many of our patients would like to get rid of the virus more quickly, thereby reducing the time in which they could potentially infect others. Additionally, many patients would greatly appreciate any intervention that shortens their acute symptomatic phase. With these two things in mind, I think many physicians may be willing to offer this safe, relatively inexpensive, and potentially beneficial procedure.
Another convincing result was the similarity between the two groups after two weeks. At this point, almost all patients had overcome the virus and were asymptomatic. In other words, while phytosomal quercetin appeared to speed recovery, both groups ultimately recovered after two weeks. This rapid recovery could be due in part to the average age of both groups, their outpatient status, and (possibly) the absence of comorbidities (although these were not clearly defined in the article).
Fortunately, most people who get Covid recover. With younger age and the absence of complicating health factors, the likelihood increases significantly. Statistics vary as to what percentage of these patients go on to develop symptoms of Long Covid, and we could certainly use more clarity on the definition and prevalence of this syndrome. It would be interesting to determine whether the quercetin intervention affects the development of Long Covid symptoms, although the small sample size would likely preclude statistically significant data.
Nevertheless, phytosomal quercetin may be an accessible and safe option for patients who want to shorten their symptomatic Covid illnesses, even if clearance is the most likely natural course of the infection.