Honey andNigella sativaagainst COVID-19 in Pakistan (HNS-COVID-PK): A multi-center placebo-controlled randomized clinical trial
Authors: Ashraf Sohaib , Ashraf Shoaib , Ashraf Moneeb , Imran Muhammad Ahmad , Kalsoom Larab , Siddiqui Uzma Nasim , Farooq Iqra , Habib Zaighum , Ashraf Sidra , Ghufran Muhammad , Akram Muhammad Kiwan , Majeed Nighat , Zain-ul-Abdin  , Akmal Rutaba , Rafique Sundas , Nawaz Khawar , Yousaf Muhammad Ismail K , Ahmad Sohail , Shahab Muhammad Sarmad , Nadeem Muhammad Faisal , Azam Muhammad , Zheng Hui , Malik Amber , Ayyaz Mahmood , Mahmud Talha , Saboor Qazi Abdul , Ahmad Ali , Ashraf Muhammad , Izhar Mateen ,   for the COALITION COVID-19 Shaikh Zayed, Hilal Abubakar , Muhammad Arz , Shaukat Zeeshan , Khaqan Ayesha , Hayat Kanwal , Arshad Shahroze , Hassan Muhammad , Abeer-bin-Awais  , Ahmad Ammara , Mughal Tayyab , Virk Abdur Rehman , Umer Muhammad , Suhail Muhammad , Zulfiqar Sibgha , Sarfraz Saulat , Anwar Muhammad Imran , Humayun Ayesha , Khokhar R A , Siddique S 
Published: November 2020

SUMMARYBACKGROUNDNo definitive treatment exists for Coronavirus Disease 2019 (COVID-19). Honey andNigella sativa(HNS) have established antiviral, antibacterial, anti-inflammatory and immunomodulatory properties. Hence, we investigated efficacy of HNS against COVID-19. wideMETHODSWe conducted a multicenter, placebo-controlled, randomized clinical trial at 4 centers in Pakistan. RT-PCR confirmed COVID-19 adults showing moderate or severe disease were enrolled in the study. Patients presenting with multi-organ failure, ventilator support, and chronic diseases (except diabetes mellitus and hypertension) were excluded. Patients were randomly assigned in 1:1 ratio to receive either honey (1 gm/Kg/day) andNigella sativaseeds (80 mg/Kg/day) or placebo up-to 13 days along with standard care. The outcomes included symptom alleviation, viral clearance, and a 30-day mortality in intention-to-treat population. This trial was registered with ClinicalTrials.gov,NCT04347382.RESULTSThree hundred and thirteen patients - 210 moderate and 103 severe - underwent randomization from April 30 to July 29, 2020. Among these, 107 were assigned to HNS whereas 103 to placebo for moderate cases. For severe cases, 50 were given HNS and 53 were given placebos. HNS resulted in ∼50% reduction in time taken to alleviate symptoms as compared to placebo (Moderate (4 versus 7 days), Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23-8.84, P<0.0001 and severe (6 versus 13 days) HR: 4.04; 95% CI, 2.46-6.64, P<0.0001). HNS also cleared the virus 4 days earlier than placebo group in moderate (6 versus 10 days, HR: 5.53; 95% CI: 3.76-8.14, P<0.0001) and severe cases (8.5 versus 12 days, HR: 4.32; 95% CI: 2.62-7.13, P<0.0001). HNS further led to a better clinical score on day 6 with normal activity resumption in 63.6% versus 10.9% among moderate cases (OR: 0.07; 95% CI: 0.03-0.13, P<0.0001) and hospital discharge in 50% versus 2.8% in severe cases (OR: 0.03; 95% CI: 0.01-0.09, P<0.0001). In severe cases, mortality rate was four-fold lower in HNS group than placebo (4% versus 18.87%, OR: 0.18; 95% CI: 0.02-0.92, P=0.029). No HNS-related adverse effects were observed.CONCLUSIONHNS significantly improved symptoms, viral clearance and mortality in COVID-19 patients. Thus, HNS represents an affordable over the counter therapy and can either be used alone or in combination with other treatments to achieve potentiating effects against COVID-19.FUNDINGFunded by Smile Welfare Organization, Shaikh Zayed Medical Complex, and Services Institute of Medical Sciences.