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

{ 'indexed': {'date-parts': [[2022, 11, 8]], 'date-time': '2022-11-08T07:41:11Z', 'timestamp': 1667893271435}, 'reference-count': 61, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2022, 11, 8]], 'date-time': '2022-11-08T00:00:00Z', 'timestamp': 1667865600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:p><jats:bold>Background:</jats:bold> 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. ' '<jats:italic>Nigella</jats:italic><jats:italic>sativa</jats:italic> 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.</jats:p><jats:p><jats:bold>Objective:</jats:bold> This ' 'study aims to investigate the effects of <jats:italic>Nigella sativa</jats:italic> 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\xa0days.</jats:p><jats:p><jats:bold>Patients and ' 'Methods:</jats:bold> 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\xa0mg ' '<jats:italic>Nigella sativa</jats:italic> through 450\xa0mg 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\xa0mg of <jats:italic>Nigella sativa</jats:italic> ' '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.</jats:p><jats:p><jats:bold>Results:</jats:bold> The <jats:italic>Nigella ' 'sativa</jats:italic>–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\xa0days, 70% showed an absence of fatigue after 4\xa0' 'days, 80% had no headache after 5\xa0days, 90% were free of rhinorrhea after 7\xa0days, and ' '86.7% of the patients had no dyspnea after 7\xa0days. Moreover, patients in the four studied ' 'groups showed a reduced median temperature after 3\xa0days of treatment. Negative results of ' 'the polymerase chain reaction (PCR) test recorded on the 7th and 14th\xa0day of therapy were ' 'superior in the <jats:italic>Nigella sativa</jats:italic> and vitamin D3 combination arm ' 'compared to those of the other studied arms where the value of the odds ratio (OR) on the ' '7th\xa0day 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.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> The results of this study showed ' 'a promising therapeutic benefit of the administration of <jats:italic>Nigella ' 'sativa</jats:italic> 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.</jats:p><jats:p><jats:bold>Clinical ' 'Trial Registration:</jats:bold><jats:ext-link>ClinicalTrials.gov</jats:ext-link>, Identifier: ' 'NCT04981743.</jats:p>', 'DOI': '10.3389/fphar.2022.1011522', 'type': 'journal-article', 'created': {'date-parts': [[2022, 11, 8]], 'date-time': '2022-11-08T07:02:23Z', 'timestamp': 1667890943000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 ' 'patients: A randomized controlled clinical trial', 'prefix': '10.3389', 'volume': '13', 'author': [ {'given': 'Shimaa A.', 'family': 'Said', 'sequence': 'first', 'affiliation': []}, {'given': 'Alsayyed', 'family': 'Abdulbaset', 'sequence': 'additional', 'affiliation': []}, {'given': 'Amal A.', 'family': 'El-Kholy', 'sequence': 'additional', 'affiliation': []}, {'given': 'Osama', 'family': 'Besckales', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nagwa A.', 'family': 'Sabri', 'sequence': 'additional', 'affiliation': []}], 'member': '1965', 'published-online': {'date-parts': [[2022, 11, 8]]}, 'reference': [ { 'key': 'B1', 'doi-asserted-by': 'publisher', 'first-page': '1914', 'DOI': '10.3390/PLANTS11151914', 'article-title': 'Bio-guided isolation of SARS-CoV-2 main protease inhibitors from ' 'medicinal plants: In vitro assay and molecular dynamics', 'volume': '11', 'author': 'Abdallah', 'year': '2022', 'journal-title': 'Plants'}, { 'key': 'B2', 'doi-asserted-by': 'publisher', 'first-page': '441', 'DOI': '10.1007/978-3-030-73234-9_29', 'article-title': 'Resveratrol as a probable multiheaded treatment approach for COVID-19', 'volume': '1328', 'author': 'Ahmadian', 'year': '2021', 'journal-title': 'Adv. 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