Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial

{ 'indexed': { 'date-parts': [[2023, 11, 11]], 'date-time': '2023-11-11T20:41:15Z', 'timestamp': 1699735275155}, 'reference-count': 69, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 11, 11]], 'date-time': '2023-11-11T00:00:00Z', 'timestamp': 1699660800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2023, 11, 11]], 'date-time': '2023-11-11T00:00:00Z', 'timestamp': 1699660800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>In the severe forms of COVID-19 and many other infectious diseases, ' 'the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as ' 'IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron ' 'are two important trace minerals, and their metabolism is tightly connected to immune system ' 'function. Numerous studies highlight the role of selenium and iron metabolism changes in the ' 'procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are ' 'synthesized based on nanochelating technology has been proved in previous studies. In the ' 'present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S ' '(containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate ' 'COVID-19 patients were evaluated.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>Laboratory-confirmed moderate COVID-19 patients were enrolled to ' 'participate in a randomized, double-blind, placebo-controlled study in two separate groups: ' 'combination of BCc1 and Hep-S (<jats:italic>N</jats:italic>\u2009=\u200962) (treatment) or ' 'placebo (<jats:italic>N</jats:italic>\u2009=\u200960) (placebo). The blood samples were taken ' 'before medications on day zero, at discharge, and 28 days after consumption to measure ' 'hematological and biochemical parameters and cytokine levels. The clinical symptoms of all ' 'the patients were recorded according to an assessment questionnaire before the start of the ' 'treatment and on days 3 and discharge day.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>The results revealed that consumption of the nanomedicines led to a ' 'significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there ' 'was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the ' 'placebo group (<jats:italic>p</jats:italic>\u2009&lt;\u20090.05). In addition, the patients ' 'in the nanomedicines group had lower TNF-α levels; accordingly, there was a 21% decrease in ' 'TNF-α level in the treatment group, while a 31% increase in this cytokine level in the ' 'placebo was observed (<jats:italic>p</jats:italic>\u2009&gt;\u20090.05). On the other hand, ' 'in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen ' 'therapy improved.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a ' 'highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising ' 'view for immunomodulation that can manage CSS.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Trial registration</jats:title>\n' ' <jats:p>Iranian Registry of Clinical Trials <jats:ext-link ' 'xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" ' 'xlink:href="https://en.irct.ir/trial/48049">RCT20170731035423N2</jats:ext-link>. Registered ' 'on June 12, 2020.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1186/s13063-023-07624-2', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 11]], 'date-time': '2023-11-11T08:02:00Z', 'timestamp': 1699689720000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in ' 'hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled ' 'clinical trial', 'prefix': '10.1186', 'volume': '24', 'author': [ {'given': 'Maryam', 'family': 'Hafizi', 'sequence': 'first', 'affiliation': []}, {'given': 'Somayeh', 'family': 'Kalanaky', 'sequence': 'additional', 'affiliation': []}, {'given': 'Saideh', 'family': 'Fakharzadeh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Pegah', 'family': 'Karimi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Atefeh', 'family': 'Fakharian', 'sequence': 'additional', 'affiliation': []}, {'given': 'Somayeh', 'family': 'Lookzadeh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Esmaeil', 'family': 'Mortaz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Maryam Sadat', 'family': 'Mirenayat', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jalal', 'family': 'Heshmatnia', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Mehrdad Bakhshayesh', 'family': 'Karam', 'sequence': 'additional', 'affiliation': []}, {'given': 'Homa', 'family': 'Zamani', 'sequence': 'additional', 'affiliation': []}, {'given': 'Alireza', 'family': 'Nadji', 'sequence': 'additional', 'affiliation': []}, { 'given': 'Mihan Pourabdollah', 'family': 'Toutkaboni', 'sequence': 'additional', 'affiliation': []}, {'given': 'Saeed', 'family': 'Oraee-Yazdani', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohammad Esmaeil', 'family': 'Akbari', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hamidreza', 'family': 'Jamaati', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9413-2295', 'authenticated-orcid': False, 'given': 'Mohammad Hassan', 'family': 'Nazaran', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2023, 11, 11]]}, 'reference': [ { 'key': '7624_CR1', 'volume-title': 'Clinical management of severe acute respiratory infection (SARI) when ' 'COVID-19 disease is suspected: interim guidance, 13 March 2020', 'author': 'Organization, W.H', 'year': '2020', 'unstructured': 'Organization, W.H. 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