Prophylactic potential of honey and Nigella sativa L. against hospital and community-based SARS-CoV-2 spread: a structured summary of a study protocol for a randomised controlled trial

Abstract

Objectives Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. Trial design The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial. Participants All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Intervention and comparator In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan. Main outcomes Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. Randomisation Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. Blinding (masking) Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking. Numbers to be randomised (sample size) 1000 participants will be enrolled in the study with 1:1 allocation. Trial Status The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. Trial registration Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Thymoquinone’s Antiviral Effects: It is Time to be Proven in the Covid-19 Pandemic Era and its Omicron Variant Surge

“…Most recently, Molnupiravir as early treatment has shown a reduced risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19 ( Jayk Bernal et al, 2021 ). furthermore, Pfizer released phase 2/3 results from the PAXLOVID trial, confirming the novel COVID-19 oral antiviral treatment’s robust efficacy in reducing the risk of hospitalization or death by 89% (within 3 days of symptom onset) and 88% (within 5 days of symptom onset) compared to placebo; no deaths in non-hospitalized, high-risk adults with COVID-19 compared to placebo ( Archive, 2021 ), in addition, PAXLOVID has been authorized by the United States Food and Drug Administration ( Ashraf et al, 2021 ) as emergency use authorization and became the first oral antiviral authorized by FDA for treatment of COVID-19 ( U.S. Food and Drug Administration, 2021a ).…”

The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial

“…Patients were randomly assigned into one of the following four groups, 30 patients in each: Group (1) patients received a total oral dose of 900 mg Nigella sativa (Baraka ® , Pharco Pharmaceuticals, Cairo, Egypt) in the form of soft gelatin capsules containing 450 mg, given as two capsules twice daily for two weeks ( Mahdavi et al, 2015 ; Ashraf et al, 2021 ) in addition to the standard therapy. Group (2) patients received 2,000 IU of vitamin D3 (Davalindi ® , Medical Union Pharma, Cairo, Egypt) in the form of 1000-IU tablets given as two tablets, once daily, in addition to the standard therapy.…”

Calcium Signals during SARS-CoV-2 Infection: Assessing the Potential of Emerging Therapies

“…Plants have a long history of being rich sources of active ingredients that are helpful against various kinds of disease, including viral infections. Accordingly, a recent study has shown that administration of Nigella sativa L. (black cumin) over 2 weeks reduces the severity of COVID-19 symptoms and elicited viral clearance [ 159 ]. The active compound in N. sativa seems to be thymoquinone, which shows high efficacy against SARS-CoV-2 according to recently published findings [ 160 , 161 ].…”