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

Abstract

Background: The coronavirus disease 2019 (COVID-19) is a novel coronavirus that causes severe infection in the respiratory system. Since the immune status plays an essential role in combating COVID-19, herbal medicines, which have an immunomodulatory effect, may help prevent and even treat COVID-19. Nigella sativa is one of the herbal medicines with antiviral and immunomodulatory activities, and its therapeutic effectiveness makes it a promising add-on therapy for COVID-19. In addition, vitamin D3 has an immunomodulatory role, but the effect of therapeutic vitamin D3 supplementation in SARS-CoV-2 infection is still not well-known. Objective: This study aims to investigate the effects of Nigella sativa and vitamin D3 as single supplemental therapies and in combination on viral clearance indicated by a negative polymerase chain reaction and the alleviation of symptoms during the study follow-up duration of 14 days. Patients and Methods: The study design was an open-label randomized controlled clinical trial conducted at the Respiratory Hospital at the Kobry El Qobba Armed Forces Medical Complex. In total, 120 COVID-19 patients with mild to moderate symptoms were randomly assigned to four groups, with thirty patients each, as follows: Group 1 received an oral dose of 900 mg Nigella sativa through 450 mg soft gelatin capsules twice daily for two weeks; Group 2 received 2,000 IU of vitamin D3 through 1000-IU tablets given as two tablets, once daily; Group 3 received 900 mg of Nigella sativa and 2,000 IU of vitamin D3 in the same manner of dosing as in the previous groups; and Group 4 was the control group. All groups received standard therapy for COVID-19 infections and clinical management of COVID-19's clinical symptoms. Results: The Nigella sativa-vitamin D3 combination in addition to the standard therapy for COVID-19 infections significantly contributed to the alleviation of most COVID-19 symptoms: 50% of patients were free of cough after 7 days, 70% showed an absence of fatigue after 4 days, 80% had no headache after 5 days, 90% were free of rhinorrhea after 7 days, and 86.7% of the patients had no dyspnea after 7 days. Moreover, patients in the four studied groups showed a reduced median temperature after 3 days of treatment. Negative results of the polymerase chain reaction (PCR) test recorded on the 7th and 14th day of therapy were superior in the Nigella sativa and vitamin D3 combination arm compared to those of the other studied arms where the value of the odds ratio (OR) on the 7th day was 0.13 with 95% CI: 0.03-0.45 and that of the 14th day was 0.09 with 95% CI: 0.02-0.3. Conclusion: The results of this study showed a promising therapeutic benefit of the administration of Nigella sativa and vitamin D3 combination in COVID-19 patients with mild to moderate symptoms. Additionally, the remarkable viral clearance in a short time interval and reduction in the severity and progression of symptoms recommended the use of this combination as an add-on therapy for the management of COVID-19 patients. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04981743.

Keywords: COVID-19; Nigella sativa; add-on therapy; complementary medicine; immunomodulation; vitamin D3.

FIGURE 1

CONSORT diagram of the study.

FIGURE 2

Stacked bar plot presenting the number (percentage) of patients corresponding to levels of cough severity among the studied groups, pre- and post-intervention. The bar plot presents the effect of the different study interventions on the levels of cough severity in patients of the four groups: (a) Group 1 received standard therapy (controls), Group 2 received NS, Group 3 received VD, and Group 4 received NS-VD combination. (b) Different levels of cough severity were defined in ascending order: absent, dry, and productive with the change in the percentage of patients (number in each group) detected pre- and 7 days post-intervention. (b) The figure clarified the remarkable decrement in the proportion of patients with productive cough among the studied groups, which revealed effect of the intervention. (c) Multiple logistic regression analysis used for evaluating the effect of the interventional therapy versus the standard therapy on cough severity showed that Nigella sativa independently reduced the odds of worsening of cough (odds ratio [OR] = 0.2, 95% CI = 0.07–0.59).

FIGURE 3

Bar plot presenting the percentage (number) of patients with positive polymerase chain reaction test at baseline and after 7 and 14 days among the studied groups. The bar plot indicated treatment failure, evidenced by absence of the viral clearance, detected by positive polymerase chain reaction (PCR) tests among the studied groups: (a) Group 1 received standard therapy (controls), Group 2 received NS, Group 3 received VD, and Group 4 received NS-VD combination. (b) Percentage (number) of patients with positive PCR test (no viral clearance) is presented on the bar chart corresponding to each study group pre- and at 7 and 14 days’ post-intervention. (c) Binary logistic regression analysis used for evaluating the effect of the interventional therapy versus the standard therapy on viral clearance evidenced by results of PCR showed that Nigella sativa alone and the Nigella sativa–vitamin D3 combination significantly reduced the odds of positive PCR at day 7 with odd ratios (OR) = 0.15 and 0.13 and 95% confidence interval (95% CI) = 0.04–0.51 and 0.03–0.45, respectively. However, only the combination significantly reduced the odds of a positive PCR at day 14 post-treatment (odds ratio [OR] = 0.09, 95% CI = 0.02–0.30).