Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial.

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host's hyperinflammatory response. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04861298.

Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host's hyperinflammatory response. Clinical Trial Registration:clinicaltrials.gov, identifier NCT04861298

A New Strategy for Somatotype Assessment Using Bioimpedance Analysis: Stratification According to Sex.

Body composition assessment is a relevant element in the biomedical field, in research and daily practice in the medical and nutritional fields, and in the management of athletes. This paper aimed to operate in an Italian sample investigating the possibility of predicting the somatotype from bioimpedance analysis and comparing the predicted results with those obtained from anthropometric measurements. This observational study was conducted with retrospective data collected from 2827 subjects. The somatotype of each subject was calculated both with the Heath-Carter method and by a multiple regression model based on bioimpedance and anthropometric parameters. Somatotypes (endomorph, mesomorph, and ectomorph) were predicted with a high goodness of fit (R2 adjusted > 0.80). Two different somatocharts were obtained from anthropometric measures and bioimpedance parameters and subsequentially compared. Bland-Altman plots showed acceptable accuracy. This study could be a first step in developing a new approach that allows the detection of a subject's somatotype via bioimpedance analysis, stratified according to sex, with a time-saving and more standardized procedure. It would allow, for example, during the COVID-19 pandemic, to minimize operator-patient contact in having measurements.

Clinical Effects of Streptococcus salivarius K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study.

Anatomical and physiological considerations indicate that the oral cavity is a primary source of the lung microbiota community, and recent studies have shown that the microbiota in the lungs contributes to immunological homeostasis, potentially altering the organ's susceptibility to viral infection, including SARS-CoV-2. It has been proposed that, in the case of viral infection, lung Gram-negative bacteria could promote the cytokine cascade with a better performance than a microbiota mainly constituted by Gram-positive bacteria. Recent observations also suggest that Prevotella-rich oral microbiotas would dominate the oral cavity of SARS-CoV-2-infected patients. In comparison, Streptococcus-rich microbiotas would dominate the oral cavity of healthy people. To verify if the modulation of the oral microbiota could have an impact on the current coronavirus disease, we administered for 14 days a well-recognized and oral-colonizing probiotic (S. salivarius K12) to hospitalized COVID-19 patients. The preliminary results of our randomized and controlled trial seem to prove the potential role of this oral strain in improving the course of the main markers of pathology, as well as its ability to apparently reduce the death rate from COVID-19. Although in a preliminary and only circumstantial way, our results seem to confirm the hypothesis of a direct involvement of the oral microbiota in the construction of a lung microbiota whose taxonomic structure could modulate the inflammatory processes generated at the pulmonary and systemic level by a viral infection.

Quercetin Phytosome® as a potential candidate for managing COVID-19.

When looking for new antiviral compounds aimed to counteract the COVID-19, a disease caused by the recently identified novel Coronavirus (SARS-CoV-2), the knowledge of the main viral proteins is fundamental. The major druggable targets of SARS-CoV-2 include 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase, and spike (S) protein. Molecular docking studies have highlighted that quercetin, a natural polyphenol belonging to the flavonol class, inhibits 3CLpro, PLpro and S proteins. Biophysical technics have then very recently confirmed that quercetin is reasonably a potent inhibitor of 3CLpro. The likely antiviral properties of quercetin are anyway challenged by its very poor oral bioavailability profile and any attempt to overcome this limit should be welcome. A phospholipid delivery form of quercetin (Quercetin Phytosome®) has been recently tested in humans to evaluate a possible improvement in oral bioavailability. After hydrolysis of the conjugated form (mainly glucuronide) of quercetin found in human plasma, the pharmacokinetics results have demonstrated an increased bioavailability rate by about 20-fold for total quercetin. It has been also observed that the presence of specific glucuronidase could yield free systemic quercetin in human body. Taking also into considerations its anti-inflammatory and thrombin-inhibitory actions, a bioavailable form of quercetin, like Quercetin Phytosome®, should be considered a possible candidate to clinically face COVID-19.

A Practical Perspective on the Use of Botanicals During the COVID-19 Pandemic: From Proven to Potential Interactions.

In this review, we examined the top 10 nutraceutical products sold in Italian pharmacies and parapharmacies as well as hypermarkets and supermarkets; in the first, three product categories saw the greatest increase in sales (vitamins and minerals, immunostimulants, and sleep products) for the 12-month period between October 2019 and October 2020 (including first pandemic wave of SARS-CoV-2). We are investigating their respective formulas and isolating the botanicals that are used to make them. Many of these products have undergone preclinical and clinical studies. We performed a systematic literature search in the MEDLINE database using PubMed and Google Scholar from November 15, 2020 to December 15, 2020 (including studies carried out between 1980 and 2020). The search terms that were used included the complete name of the medicinal plant in English or Latin and the terms "cytochrome" or "drug interactions," crossing, respectively, the Latin name and English common names with "cytochrome" and "drug interactions." The search included in vitro and in vivo studies describing the effects of interaction between the plant (extract or botanical medicine) and human cytochromes. Despite their great complexity, there is decidedly limited clinical data on botanical medicine. In fact, of the 28 botanicals that were examined, only 2 (Citrus paradisi and Rhodiola rosea) show in vivo pharmacological interactions in human subjects. On the contrary, for the other botanicals, there is only weak evidence of dubious clinical significance or potential interactions shown in animal models or in vitro without clinical confirmation. This study provides a rational assessment of the most widely used products, including those used in self-medication, to simplify patient management during the COVID-19 health emergency.

Potential Clinical Benefits of Quercetin in the Early Stage of COVID-19: Results of a Second, Pilot, Randomized, Controlled and Open-Label Clinical Trial.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing global pandemic known as COVID-19. Based on the potential antiviral role of quercetin, and on its described anti-blood clotting, anti-inflammatory and antioxidant properties, we hypothesize that subjects with mild COVID-19 treated with Quercetin Phytosome® (QP), a novel bioavailable form of quercetin, may have a shorter time to virus clearance, a milder symptomatology, and higher probabilities of a benign earlier resolution of the disease. METHODS: In our 2-week, randomized, open-label, and controlled clinical study, we have enrolled 42 COVID-19 outpatients. Twenty-one have been treated with the standard of care (SC), and 21 with QP as add-on supplementation to the SC. Our main aims were to check virus clearance and symptoms. RESULTS: The interim results reveal that after 1 week of treatment, 16 patients of the QP group were tested negative for SARS-CoV-2 and 12 patients had all their symptoms diminished; in the SC group, 2 patients were tested SARS-CoV-2 negative and 4 patients had their symptoms partially improved. By 2 weeks, the remaining 5 patients of the QP group tested negative for SARS-CoV-2, whereas in the SC group out of 19 remaining patients, 17 tested negatives by week 2, one tested negative by week 3 and one patient, still positive, expired by day 20. Concerning blood parameters, the add on therapy with QP, reduced LDH (-35.5%), Ferritin (-40%), CRP (-54.8%) and D-dimer (-11.9%). CONCLUSION: QP statistically shortens the timing of molecular test conversion from positive to negative, reducing at the same time symptoms severity and negative predictors of COVID-19.

Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study.

BACKGROUND: Quercetin, a well-known naturally occurring polyphenol, has recently been shown by molecular docking, in vitro and in vivo studies to be a possible anti-COVID-19 candidate. Quercetin has strong antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties, and it is characterized by a very high safety profile, exerted in animals and in humans. Like most other polyphenols, quercetin shows a very low rate of oral absorption and its clinical use is considered by most of modest utility. Quercetin in a delivery-food grade system with sunflower phospholipids (Quercetin Phytosome®, QP) increases its oral absorption up to 20-fold. METHODS: In the present prospective, randomized, controlled, and open-label study, a daily dose of 1000 mg of QP was investigated for 30 days in 152 COVID-19 outpatients to disclose its adjuvant effect in treating the early symptoms and in preventing the severe outcomes of the disease. RESULTS: The results revealed a reduction in frequency and length of hospitalization, in need of non-invasive oxygen therapy, in progression to intensive care units and in number of deaths. The results also confirmed the very high safety profile of quercetin and suggested possible anti-fatigue and pro-appetite properties. CONCLUSION: QP is a safe agent and in combination with standard care, when used in early stage of viral infection, could aid in improving the early symptoms and help in preventing the severity of COVID-19 disease. It is suggested that a double-blind, placebo-controlled study should be urgently carried out to confirm the results of our study.

Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus.

The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100,000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an α-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.