Honey and Nigella sativa against COVID‐19 in Pakistan (HNS‐COVID‐PK): A multicenter placebo‐controlled randomized clinical trial

Abstract

Until now, no specific and effective treatment exists for coronavirus disease 2019 (COVID‐19). Since honey and Nigella sativa (HNS) have established antiviral, antibacterial, antiinflammatory, antioxidant, and immunomodulatory properties, we tested their efficacy for this disease in a multicenter, placebo‐controlled, and randomized clinical trial at four medical care facilities in Pakistan. RT‐PCR confirmed COVID‐19 adults showing moderate or severe disease were enrolled in the trial. Patients were randomly assigned in a 1:1 ratio to receive either honey (1 g kg−1 day−1) and Nigella sativa seeds (80 mg kg−1 day−1) or a placebo for up to 13 days along with standard care. The outcomes included symptoms' alleviation, viral clearance, and 30‐day mortality in the intention‐to‐treat population. Three hundred and thirteen patients, 210 with moderate and 103 with severe disease, underwent randomization from April 30 to July 29, 2020. Among the moderate cases, 107 were assigned to HNS, whereas 103 were assigned to the placebo group. Among the severe cases, 50 were given HNS, and 53 were given the placebo. HNS resulted in ~50% reduction in time taken to alleviate symptoms as compared to placebo (moderate cases: 4 vs. 7 days, Hazard Ratio [HR]: 6.11; 95% Confidence Interval [CI]: 4.23–8.84, p < 0.0001 and for severe cases: 6 vs. 13 days, HR: 4.04; 95% CI: 2.46–6.64; p < 0.0001). HNS also cleared the virus earlier than placebo in both moderate cases (6 vs. 10 days, HR: 5.53; 95% CI: 3.76–8.14, p < 0.0001) and severe cases (8.5 vs. 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% vs. 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, the mortality rate was less than 1/4th in the HNS group than in placebo (4% vs. 18.87%, OR: 0.18; 95% CI: 0.02–0.92, p = 0.029). No HNS‐related adverse effects were observed. HNS, compared with placebo, significantly improved symptoms, expedited viral load clearance, and reduced mortality in COVID‐19 patients. This trial was registered on April 15, 2020 with ClinicalTrials.gov Identifier: NCT04347382.

The effect of Nigella sativa on the risk of mortality in patients with COVID‐19: A systematic review and meta‐analysis of randomized trials

“…Of these, two studies were excluded since they were observational studies. Eventually, three randomized trials (Al-Haidari, Faiq, & Ghareeb, 2021;Ashraf et al, 2022;Karimi et al, 2021) were included in this meta-analysis, with a total of 1,113 patients with COVID-19. Characteristics of the included trials is summarized in Table 1.…”

“…Two of the included trials (Al-Haidari et al, 2021;Karimi et al, 2021) which evaluated the effect of the use of N. sativa on the risk of mortality in patients with COVID-19 were of randomized, open-label design. In contrast, the remaining trial (Ashraf et al, 2022) was of randomized, double-blind, placebo-controlled design. The three included trials (Al-Haidari et al, 2021;Ashraf et al, 2022;Karimi et al, 2021) were performed in Pakistan (Ashraf et al, 2022), Iraq (Al-Haidari et al, 2021), and Iran (Karimi et al, 2021) respectively.…”

“…In contrast, the remaining trial (Ashraf et al, 2022) was of randomized, double-blind, placebo-controlled design. The three included trials (Al-Haidari et al, 2021;Ashraf et al, 2022;Karimi et al, 2021) were performed in Pakistan (Ashraf et al, 2022), Iraq (Al-Haidari et al, 2021), and Iran (Karimi et al, 2021) respectively. The regimen of N. sativa administered to the intervention group varied across the three trials: in the trial reported by Ashraf et al (2022), N. sativa was administered orally at a dose of 80 mg/kg in 2-3 divided doses for 13 days; in the trial reported by Al-Haidari et al (2021), N. sativa was administered orally at a dose of 40 mg/kg once daily for 14 days; whereas in the trial reported by Karimi et al (2021), N. sativa was administered orally at a dose of 500 mg twice daily for 7 days.…”

“…The overall risk of bias assessed by RoB 2 is presented in Table 1 The meta-analysis of three trials (Al-Haidari et al, 2021;Ashraf et al, 2022;Karimi et al, 2021) revealed significantly reduced odds of mortality with the use of N. sativa relative to the non-use of N. sativa in patients with COVID-19. The estimated effect indicates mortality benefits (Figure 1; pooled odds ratio = 0.22; 95% confidence interval 0.08 to 0.62, I 2 = 0%, p = .38, n = 1,113), and with adequate evidence to refute the null hypothesis of "no significant difference," at the current sample size.…”

Culinary spices and herbs in managing early and long‐COVID‐19 complications: A comprehensive review

“…However, these findings are inadequate to establish that Giloy Ghan Vati lowers the incidence of COVID‐19 (Thakar, Panara, Shah et al, 2022). In another clinical trial, where honey and Nigella sativa was given along with standard care, it was observed that this treatment improves symptoms, expedites viral clearance, and reduces mortality in COVID‐19 patients (Ashraf et al, 2023). In another clinical trial, AYUSH‐64 (a multi‐herbal formulation of Alstonia scholaris , Picrorhiza kurroa Royle , Swertia chirata Pexbex .…”