scholarly journals 1524 Design and Implementation Of ICE-COVID, A Double-Blind Randomised Placebo-Controlled Trial on The Efficacy of Iota-Carrageenan Nasal and Throat Spray for Covid-19 Prophylaxis

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
J Y Lim ◽  
Z M Jessop ◽  
J A G Gibson ◽  
T H Jovic ◽  
E Combellack ◽  
...  
Keyword(s):  
Viral Entry ◽  
Controlled Trial ◽  
Host Cells ◽  
Upper Respiratory Tract ◽  
Double Blind ◽  
Edible Seaweed ◽  
Surgical Department ◽  
Surface Receptors ◽  
Tract Infections

Abstract Introduction The severity of Covid-19 infection is associated with viral load. For infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus to attach to the host cell surface receptors. Iota-carrageenan (I-C), a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a range of viruses in clinical trials, through prevention of viral entry into respiratory host cells and in-vitro activity against SARS-CoV-2. Our aim, as an academic surgical department, was to design and implement a clinical trial to investigate whether I-C nasal and throat sprays are effective in reducing the rate and severity of Covid-19 infection. Method The study is a single centre, double-blinded randomised controlled trial. Recruitment of 480 participants aged ≥18 years without previous Covid-19 infection and who have not yet been vaccinated, commenced in December 2020. Participants are randomised to either the treatment (0.12% I-C in 0.5% saline spray) or placebo (0.5% saline spray) arm and will prophylactically apply the spray to their nose and throat while completing a daily symptom tracker for a total of 10 weeks. The primary outcome is the acquisition of Covid-19 infection. Secondary outcomes include symptom type, severity and duration, subsequent familial/household Covid-19 infection and infection with non-Covid-19 upper respiratory tract infections. Discussion Our hypothesis is that I-C sprays will reduce SARS-CoV-2 attachment to the naso- and oropharyngeal mucosal epithelial cells thus reducing the effective viral infective dose. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Trial registration number NCT04590365

scholarly journals Multi-Strain Probiotic Supplementation with a Product Containing Human-Native S. salivarius K12 in Healthy Adults Increases Oral S. salivarius

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4392
Author(s):  
Karina Cernioglo ◽  
Karen M. Kalanetra ◽  
Anna Meier ◽  
Zachery T. Lewis ◽  
Mark A. Underwood ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Amplicon Sequencing ◽  
Healthy Adults ◽  
Oral Microbiome ◽  
Placebo Control ◽  
Upper Respiratory Tract ◽  
Double Blind ◽  
16S Rrna Amplicon Sequencing ◽  
Supplementation Period ◽  
Tract Infections

Streptococcus salivarius (S. salivarius) K12 supplementation has been found to reduce the risk of recurrent upper respiratory tract infections. Yet, studies have not reported the effect of supplementation on oral S. salivarius K12 levels or the salivary microbiome. This clinical trial was designed to determine how supplementation with S. salivarius K12 influences the oral microbiome. In a randomized, double-blind, placebo-controlled trial, 13 healthy adults received a probiotic powder (PRO) containing Lactobacillus acidophilus, Bifidobacterium lactis, and S. salivarius K12 and 12 healthy adults received a placebo-control powder (CON) (n = 12) for 14 consecutive days. Oral S. salivarius K12 and total bacteria were quantified by qPCR and the overall oral microbiome was measured using 16S rRNA amplicon sequencing. Supplementation significantly increased mean salivary S. salivarius K12 levels by 5 logs compared to baseline for the PRO group (p < 0.0005), which returned to baseline 2 weeks post-supplementation. Compared with the CON group, salivary S. salivarius K12 was 5 logs higher in the PRO group at the end of the supplementation period (p < 0.001). Neither time nor supplementation influenced the overall oral microbiome. Supplementation with a probiotic cocktail containing S. salivarius K12 for two weeks significantly increased levels of salivary S. salivarius K12.

scholarly journals Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial

2021 ◽  
pp. 1-12
Author(s):  
A. Damholt ◽  
M.K. Keller ◽  
K. Baranowski ◽  
B. Brown ◽  
A. Wichmann ◽  
...  
Keyword(s):  
General Practitioner ◽  
Respiratory Tract ◽  
Controlled Trial ◽  
Oral Intake ◽  
Upper Respiratory Tract ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Upper Respiratory ◽  
Tract Infections ◽  
Cluster 2

Acute upper respiratory tract infections (URTIs) are caused by numerous viruses and bacteria. URTIs can be a cause of morbidity and are among the most common reasons for visiting healthcare practitioners and prescribing antibiotics to children in addition to causing absenteeism from school and work. Oral intake of Lacticaseibacillus rhamnosus GG DSM 33156 has shown beneficial health effects in several clinical trials, primarily relating to immune function and gastrointestinal health in children and adults. It has also been suggested that oral intake of L. rhamnosus GG DSM 33156 can reduce the incidence rate and alleviate symptoms of URTIs in children. We here report the results of a randomised, double-blind, placebo-controlled trial of 619 children aged 2-6 years conducted at a single centre in Scotland. The children, who were in day care or primary school, were followed over a 16-week intervention period with 309 randomised in the active group and 310 in the placebo group. The parents or guardians reported a daily healthcare status and any presumed episodes of URTI, which were subsequently confirmed by a general practitioner. The investigational product was well tolerated in the trial. Although a general trend towards a beneficial effect was observed, this trial did not demonstrate that L. rhamnosus GG DSM 33156 significantly reduced the incidence of URTIs, diagnosed by a general practitioner according to prespecified criteria (primary endpoint). Moreover, none of the secondary efficacy endpoints were met. Applying a Ward’s hierarchical clustering, two separate clusters, focussing on four quality of life-related endpoints, were identified. Cluster 1 was associated with more severe URTI characteristics than cluster 2. Cluster 2 was significantly enriched with children who consumed the product, indicating that the symptoms children experience during an URTI are alleviated by the intake of L. rhamnosus GG DSM 33156. The study is registered at ClinicalTrials.gov ID: NCT03636191.

scholarly journals A mixture of essential oils from three Cretan Aromatic Plants (thyme, Greek sage and Cretan dittany, CAPeo) inhibits SASR-CoV-2 proliferation: in vitro evidence and a Proof-of-Concept intervention study in mild ambulatory COVID-19-positive patients

2021 ◽  
Author(s):  
Christos Lionis ◽  
Ioannis Karakasiliotis ◽  
Elena Petelos ◽  
Manolis Linardakis ◽  
Athanasios Diamantakis ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Intervention Study ◽  
Controlled Trial ◽  
Vero Cells ◽  
Upper Respiratory Tract ◽  
Proof Of Concept ◽  
Significant Amelioration ◽  
Tract Infections

AbstractThe need for therapeutic regimens for the non-critically ill patients of the COVID-19 pandemic remains unmet. In this line, repurposing existing drugs, against known or predicted SARS-CoV-2 protein actions, has been advanced, while natural products have also been tested. Previous work has shown that a Cretan Aromatic Plant (Thymbra capitata (L.) Cav., Salvia fruticosa Mill. and Origanum dictamnus L.) essential oil mixture (CAPeo) has a remarkable in vitro antiviral activity against Influenza A & B and Rhinovirus 14 strains, decreasing the symptoms of upper respiratory tract infections, while proven safe in experimental animals and humans. Here, we tested CAPeo in VERO cells infected with SASR-CoV-2. We report that this mixture, at similar concentrations as those previously reported, exhibits a remarkable antiviral activity. Administration of 1 ml of a 1.5% CAPeo in olive oil, in a Proof-of-Concept intervention study in SARS-CoV-2-positive, exhibiting mild COVID-19 symptoms, humans resulted in a significant amelioration of general and local symptoms of the disease. We conclude that CAPeo may be a valuable addition for the prevention and/or treatment of mild COVID-19 ambulatory patients, pending a confirmation through a prospective randomized controlled trial in humans (NCT04705753).

Safety and Tolerability of Anti-IL-5 Monoclonal Antibody (Mepolizumab) Therapy in Patients with HES: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2694-2694
Author(s):  
Amy D. Klion ◽  
Marc E. Rothenberg ◽  
John J. Murray ◽  
Anish Singh ◽  
Hans-Uwe Simon
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Eosinophil Count ◽  
Controlled Trial ◽  
Blood Eosinophil ◽  
Upper Respiratory Tract ◽  
Double Blind ◽  
Blood Eosinophil Count ◽  
Double Blind Placebo ◽  
Tract Infections

Abstract Mepolizumab is a fully humanized monoclonal IgG antibody which binds to interleukin 5 (IL-5) with high affinity and specificity, preventing it from binding to IL-5 receptors on the eosinophil cell surface. Since IL-5 is central in eosinophil proliferation, differentiation, mobilization, activation, and survival, yet has limited effects on other cell types, IL-5 inhibition should inhibit the production and activity of eosinophils without affecting the function of other immune cells. Reducing the blood eosinophil count is a critical therapeutic objective in patients with eosinophil-driven diseases, such as hypereosinophilic syndrome (HES). The safety and tolerability of mepolizumab has been evaluated, as a secondary endpoint, in a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. The trial enrolled 85 patients with HES (blood eosinophil count >1500/μl for ≥6 months with documented eosinophilia-related organ involvement or dysfunction and no known cause of eosinophilia), who were negative for the FIP1L1-PDGFRα gene rearrangement. Blood eosinophil levels were stabilized at <1000 cells/μL on 20–60 mg/day prednisone monotherapy during a run-in period of up to 6 weeks, then patients were randomized to intravenous mepolizumab 750 mg (n=43) or saline (placebo; n=42) every 4 weeks for 36 weeks (final infusion at Week 32). Overall, 98% of placebo-treated and 93% of mepolizumab-treated patients reported an adverse event during treatment. The most common of these were fatigue (26% on placebo vs 30% on mepolizumab), pruritus (21% vs 28%), headache (21% vs 23%), and arthralgia (17% vs 21%). The only significant differences between the treatment groups were in pharyngolaryngeal pain (14% on placebo vs 2% on mepolizumab; P=0.027) and pain in extremity (12% on placebo vs 2% on mepolizumab; P=0.047); none of the adverse events was significantly more frequent with mepolizumab than with placebo. A greater than 8% difference in adverse event reporting for the mepolizumab vs placebo arms was noted for upper respiratory tract infections, myalgia, rhinitis, bronchitis, and urticaria. Serious adverse events were reported in 5 patients on placebo (7 events) and 7 patients on mepolizumab (14 events, including 1 death due to a cardiac arrest), but none was considered treatment related. Withdrawals due to adverse events (4 patients on placebo; 1 patient on mepolizumab) were also considered unrelated to treatment. Laboratory tests (hematology, clinical chemistry, and urinalysis), vital signs, and ECG findings did not raise any major safety concerns. In conclusion, this study, which is currently the largest placebo-controlled trial involving exclusively patients with HES, indicates that mepolizumab is safe and well tolerated in this patient population.

scholarly journals Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 437
Author(s):  
Dean Gilham ◽  
Audrey L. Smith ◽  
Li Fu ◽  
Dalia Y. Moore ◽  
Abenaya Muralidharan ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Host Cells ◽  
Protein Inhibitor ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Surface Receptors ◽  
Bet Inhibitor ◽  
Epigenetic Machinery ◽  
Unexplored Area

Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression of cell surface receptors involved in SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4 or CD26) in SARS-CoV-2 permissive cells. Moreover, we show that apabetalone inhibits SARS-CoV-2 infection in vitro to levels comparable to those of antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics.

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