Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial

DOI record: { "DOI": "10.1007/s10787-022-00939-7", "ISSN": [ "0925-4692", "1568-5608" ], "URL": "http://dx.doi.org/10.1007/s10787-022-00939-7", "abstract": "<jats:title>Abstract</jats:title><jats:p>Recent evidence points to a potential therapeutic role for glycyrrhizin(GR) and boswellic acids (BA) in the treatment of COVID-19 but conclusive evidence is lacking. Our aim is to investigate the efficacy of GR + BA versus placebo for the treatment of hospitalized patients with moderate SARS-CoV-2 or COVID-19 variants infection. The current study is a randomized, double-blind, placebo-controlled, single-center trial. Patients with SARS-CoV-2 or COVID-19 variants diagnosed by PCR test who were admitted to Sohag University hospital were eligible if they were at least 18 years of age and had moderate symptoms. Patients were randomly assigned to receive oral GR capsule (60 mg) and BA (200 mg) twice daily for 14 days or a matching placebo. All patients also received treatment with the institutional protocol for COVID-19. The primary outcome was mortality and time to recovery. Secondary outcome was clinical status score, 14 days after receiving study drugs. Adverse events from use of study drugs have been evaluated for up to 14 days. The trial is registered at ClinicalTrials.gov (Identifier NCT04487964). During the 6-month enrollment period (June-November, 2021) only 50 patients (54% women; median age 60 years, IQR 54–65) met eligibility and were randomly assigned. Evaluation of the primary outcome at 14 days showed that there were five deaths in the placebo group and no deaths in the GR + BA group. With regard to recovery time, it was significantly shorter (<jats:italic>p</jats:italic> = 0.0001) in the group receiving GR + BA capsule compared to the placebo group (median 7.0; IQR 6.0–8.0 days vs. median 12.5; IQR 12–20 days). Clinical status on the ordinal score scale as a secondary outcome showed a significant difference between the GR + BA group (median (IQR) score, 2 [2–3]) and placebo groups (mean (IQR) score, 3 [3–5.5]). There was a significant decrease in CRB (<jats:italic>p</jats:italic> = 0.000041) in GR + BA compared with the placebo group. In conclusion, this safe, inexpensive, antiviral, immunomodulating and anti-inflammatory combination may be considered for use in mild to moderate infections of SARS-CoV-2 or COVID-19 variants. The study is limited by the small sample size; therefore, larger randomized trials are required.</jats:p>", "alternative-id": [ "939" ], "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "4 February 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "8 February 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "1 March 2022" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Conflict of interest", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "All authors declare no competing interests." }, { "group": { "label": "Ethical approval", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "The study was approved by the local ethical committee of the Faculty of Medicine, Assiut University, Egypt, complying with international standards of clinical trials (IRB No: 17101070; 6/5/2020) and was registered on ClinicalTrials.gov (Identifier NCT04487964)." }, { "group": { "label": "Consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "Informed consent to participate in the study has been obtained from participants and a form of consent is included as supplement." } ], "author": [ { "ORCID": "http://orcid.org/0000-0002-6462-0917", "affiliation": [], "authenticated-orcid": false, "family": "Gomaa", "given": "Adel A.", "sequence": "first" }, { "affiliation": [], "family": "Mohamed", "given": "Hamdy S.", "sequence": "additional" }, { "affiliation": [], "family": "Abd-ellatief", "given": "Rasha B.", "sequence": "additional" }, { "affiliation": [], "family": "Gomaa", "given": "Mohamed A.", "sequence": "additional" }, { "affiliation": [], "family": "Hammam", "given": "Doaa S.", "sequence": "additional" } ], "clinical-trial-number": [ { "clinical-trial-number": "nct04487964", "registry": "10.18810/clinical-trials-gov" } ], "container-title": [ "Inflammopharmacology" ], "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2022, 3, 1 ] ], "date-time": "2022-03-01T17:03:13Z", "timestamp": 1646154193000 }, "deposited": { "date-parts": [ [ 2022, 3, 25 ] ], "date-time": "2022-03-25T12:52:04Z", "timestamp": 1648212724000 }, "funder": [ { "DOI": "10.13039/501100009169", "doi-asserted-by": "crossref", "name": "Assiut University" } ], "indexed": { "date-parts": [ [ 2022, 4, 6 ] ], "date-time": "2022-04-06T02:11:00Z", "timestamp": 1649211060561 }, "is-referenced-by-count": 0, "issn-type": [ { "type": "print", "value": "0925-4692" }, { "type": "electronic", "value": "1568-5608" } ], "issue": "2", "issued": { "date-parts": [ [ 2022, 3, 1 ] ] }, "journal-issue": { "issue": "2", "published-print": { "date-parts": [ [ 2022, 4 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 3, 1 ] ], "date-time": "2022-03-01T00:00:00Z", "timestamp": 1646092800000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2022, 3, 1 ] ], "date-time": "2022-03-01T00:00:00Z", "timestamp": 1646092800000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1007/s10787-022-00939-7.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1007/s10787-022-00939-7/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1007/s10787-022-00939-7.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "page": "477-486", "prefix": "10.1007", "published": { "date-parts": [ [ 2022, 3, 1 ] ] }, "published-online": { "date-parts": [ [ 2022, 3, 1 ] ] }, "published-print": { "date-parts": [ [ 2022, 4 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1007/s00894-021-04816-y", "author": "S Ahmad", "doi-asserted-by": "publisher", "first-page": "206", "issue": "7", "journal-title": "J Mol Model", "key": "939_CR1", "unstructured": "Ahmad S, Waheed Y, Abro A, Abbasi SW, Ismail S (2021) Molecular screening of glycyrrhizin-based inhibitors against ACE2 host receptor of SARS-CoV-2. 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