Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19

{ 'indexed': {'date-parts': [[2023, 1, 19]], 'date-time': '2023-01-19T06:09:29Z', 'timestamp': 1674108569894}, 'reference-count': 56, 'publisher': 'MDPI AG', 'issue': '3', 'license': [ { 'start': { 'date-parts': [[2023, 1, 17]], 'date-time': '2023-01-17T00:00:00Z', 'timestamp': 1673913600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Spore-based Bacillus probiotic treatment improves intestinal health. The intestinal ' 'microbiota influences both the innate and adaptive immune responses. As such, the influence ' 'of ongoing spore-based probiotic treatment (five probiotic strains of Bacillus) on the ' 'clinical outcomes of mild COVID-19 was evaluated in this retrospective, observational study. ' 'Demographics, medical history, probiotic use, and COVID-19 symptom information were ' 'collected. The study included 120 patients with a PCR-confirmed SARS-CoV-2 infection and mild ' 'COVID-19 symptoms. The probiotic group (n = 60) comprised patients with ongoing probiotic ' 'treatment (≥1 month); the control group comprised patients not taking probiotics (n = 60). ' 'The primary outcome was time to symptom resolution; secondary outcomes included time to fever ' 'resolution and presence of digestive symptoms. The probiotic group had a significantly ' 'shorter time to symptom resolution (mean (95% confidence interval) days: control group, 8.48 ' '(6.56, 10.05); probiotic group, 6.63 (5.56; 6.63); p = 0.003) and resolution of fever ' '(control group, 2.67 (1.58, 3.61); probiotic group, 1.48 (1.21, 2.03); p &lt; 0.001). More ' 'patients in the probiotic group (n = 53) than in the control group (n = 34) did not have ' 'digestive symptoms (p &lt; 0.001). Among adults with mild COVID-19, participants receiving ' 'ongoing probiotic treatment had a shorter clinical course, and fewer had digestive symptoms ' 'compared with those not taking probiotics.</jats:p>', 'DOI': '10.3390/nu15030488', 'type': 'journal-article', 'created': {'date-parts': [[2023, 1, 18]], 'date-time': '2023-01-18T07:31:11Z', 'timestamp': 1674027071000}, 'page': '488', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves ' 'Outcomes of Mild COVID-19', 'prefix': '10.3390', 'volume': '15', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-6327-6608', 'authenticated-orcid': False, 'given': 'Adrian', 'family': 'Catinean', 'sequence': 'first', 'affiliation': []}, {'given': 'Anamaria', 'family': 'Sida', 'sequence': 'additional', 'affiliation': []}, {'given': 'Celina', 'family': 'Silvestru', 'sequence': 'additional', 'affiliation': []}, {'given': 'Gheorghe G.', 'family': 'Balan', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2023, 1, 17]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '944', 'DOI': '10.1053/j.gastro.2020.05.048', 'article-title': 'Alterations in Gut Microbiota of Patients with COVID-19 during Time of ' 'Hospitalization', 'volume': '159', 'author': 'Zuo', 'year': '2020', 'journal-title': 'Gastroenterology'}, { 'key': 'ref_2', 'unstructured': 'WHO (2023, January 16). Coronavirus (COVID-19) Dashboard. Available ' 'online: ' 'https://covid19.who.int/#:~:text=Globally%2C%20as%20of%204%3A54pm,vaccine%20doses%20have%20been%20administered.'}, { 'key': 'ref_3', 'doi-asserted-by': 'crossref', 'first-page': 'j5145', 'DOI': '10.1136/bmj.j5145', 'article-title': 'The role of the gut microbiome in systemic inflammatory disease', 'volume': '360', 'author': 'Clemente', 'year': '2018', 'journal-title': 'BMJ'}, { 'key': 'ref_4', 'doi-asserted-by': 'crossref', 'first-page': '9', 'DOI': '10.1038/s41577-022-00727-y', 'article-title': 'The impact of the gut microbiome on extra-intestinal autoimmune ' 'diseases', 'volume': '23', 'author': 'Miyauchi', 'year': '2023', 'journal-title': 'Nat. Rev. Immunol.'}, { 'key': 'ref_5', 'doi-asserted-by': 'crossref', 'first-page': '4', 'DOI': '10.4161/gmic.19320', 'article-title': 'The role of gut microbiota in immune homeostasis and autoimmunity', 'volume': '3', 'author': 'Wu', 'year': '2012', 'journal-title': 'Gut Microbes'}, { 'key': 'ref_6', 'doi-asserted-by': 'crossref', 'unstructured': 'Han, S.K., Shin, Y.J., Lee, D.Y., Kim, K.M., Yang, S.J., Kim, D.S., ' 'Choi, J.W., Lee, S., and Kim, D.H. (2021). Lactobacillus rhamnosus ' 'HDB1258 modulates gut microbiota-mediated immune response in mice with ' 'or without lipopolysaccharide-induced systemic inflammation. BMC ' 'Microbiol., 21.', 'DOI': '10.1186/s12866-021-02192-4'}, { 'key': 'ref_7', 'doi-asserted-by': 'crossref', 'first-page': '750969', 'DOI': '10.3389/fimmu.2021.750969', 'article-title': 'SARS-CoV-2 Nsp5 Activates NF-kappaB Pathway by Upregulating SUMOylation ' 'of MAVS', 'volume': '12', 'author': 'Li', 'year': '2021', 'journal-title': 'Front. Immunol.'}, { 'key': 'ref_8', 'doi-asserted-by': 'crossref', 'first-page': '229', 'DOI': '10.1111/lam.13334', 'article-title': 'Probiotics and COVID-19: Is there any link?', 'volume': '71', 'author': 'Akour', 'year': '2020', 'journal-title': 'Lett. Appl. Microbiol.'}, { 'key': 'ref_9', 'doi-asserted-by': 'crossref', 'first-page': 'e00228-20', 'DOI': '10.1128/CMR.00228-20', 'article-title': 'Tools and Techniques for Severe Acute Respiratory Syndrome Coronavirus ' '2 (SARS-CoV-2)/COVID-19 Detection', 'volume': '34', 'author': 'LeBlanc', 'year': '2021', 'journal-title': 'Clin. Microbiol. Rev.'}, { 'key': 'ref_10', 'doi-asserted-by': 'crossref', 'first-page': '648', 'DOI': '10.1053/j.gastro.2021.10.040', 'article-title': 'Potential long coronavirus disease 2019 gastrointestinal symptoms 6 ' 'months after coronavirus infection are associated with mental health ' 'symptoms', 'volume': '162', 'author': 'Blackett', 'year': '2022', 'journal-title': 'Gastroenterology'}, { 'key': 'ref_11', 'doi-asserted-by': 'crossref', 'first-page': '766', 'DOI': '10.14309/ajg.0000000000000620', 'article-title': 'Clinical Characteristics of COVID-19 Patients With Digestive Symptoms ' 'in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study', 'volume': '115', 'author': 'Pan', 'year': '2020', 'journal-title': 'Am. J. Gastroenterol.'}, { 'key': 'ref_12', 'doi-asserted-by': 'crossref', 'unstructured': 'Nguyen, Q.V., Chong, L.C., Hor, Y.Y., Lew, L.C., Rather, I.A., and Choi, ' 'S.B. (2022). Role of Probiotics in the Management of COVID-19: A ' 'Computational Perspective. Nutrients, 14.', 'DOI': '10.3390/nu14020274'}, { 'key': 'ref_13', 'doi-asserted-by': 'crossref', 'unstructured': 'Rossini, V., Tolosa-Enguis, V., Frances-Cuesta, C., and Sanz, Y. (2022). ' 'Gut microbiome and anti-viral immunity in COVID-19. Crit. Rev. Food Sci. ' 'Nutr., 1–16.', 'DOI': '10.1080/10408398.2022.2143476'}, { 'key': 'ref_14', 'doi-asserted-by': 'crossref', 'first-page': '582', 'DOI': '10.1016/j.arcmed.2021.03.002', 'article-title': 'Probiotics in Prevention and Treatment of COVID-19: Current Perspective ' 'and Future Prospects', 'volume': '52', 'author': 'Kurian', 'year': '2021', 'journal-title': 'Arch. Med. Res.'}, { 'key': 'ref_15', 'doi-asserted-by': 'crossref', 'first-page': '449', 'DOI': '10.2146/ajhp090168', 'article-title': 'Probiotics', 'volume': '67', 'author': 'Williams', 'year': '2010', 'journal-title': 'Am. J. Health Syst. Pharm.'}, { 'key': 'ref_16', 'doi-asserted-by': 'crossref', 'first-page': '4347', 'DOI': '10.3390/nu13124347', 'article-title': 'Effect and Tolerability of a Nutritional Supplement Based on a ' 'Synergistic Combination of beta-Glucans and Selenium-and Zinc-Enriched ' 'Saccharomyces cerevisiae (ABB C1((R))) in Volunteers Receiving the ' 'Influenza or the COVID-19 Vaccine: A Randomized, Double-Blind, ' 'Placebo-Controlled Study', 'volume': '13', 'author': 'Rodriguez', 'year': '2021', 'journal-title': 'Nutrients'}, { 'key': 'ref_17', 'doi-asserted-by': 'crossref', 'unstructured': 'Leal-Martinez, F., Abarca-Bernal, L., Garcia-Perez, A., Gonzalez-Tolosa, ' 'D., Cruz-Cazares, G., Montell-Garcia, M., and Ibarra, A. (2022). Effect ' 'of a Nutritional Support System to Increase Survival and Reduce ' 'Mortality in Patients with COVID-19 in Stage III and Comorbidities: A ' 'Blinded Randomized Controlled Clinical Trial. Int. J. Environ. Res. ' 'Public Health, 19.', 'DOI': '10.3390/ijerph19031172'}, { 'key': 'ref_18', 'doi-asserted-by': 'crossref', 'first-page': 'e0168222', 'DOI': '10.1128/spectrum.01682-22', 'article-title': 'Randomized, Double-Blind, Placebo-Controlled Trial of a Throat Spray ' 'with Selected Lactobacilli in COVID-19 Outpatients', 'volume': '10', 'author': 'Cauwenberghs', 'year': '2022', 'journal-title': 'Microbiol. Spectr.'}, { 'key': 'ref_19', 'doi-asserted-by': 'crossref', 'unstructured': 'Marzorati, M., Abbeele, P.V.D., Bubeck, S.S., Bayne, T., Krishnan, K., ' 'Young, A., Mehta, D., and DeSouza, A. (2020). Bacillus subtilis HU58 and ' 'Bacillus coagulans SC208 Probiotics Reduced the Effects of ' 'Antibiotic-Induced Gut Microbiome Dysbiosis in an M-SHIME® Model. ' 'Microorganisms, 8.', 'DOI': '10.3390/microorganisms8071028'}, { 'key': 'ref_20', 'first-page': '15', 'article-title': 'The effect of Probiotic Bacillus Subtilis HU58 on Immune Function in ' 'Healthy Human', 'volume': '70', 'author': 'Dound', 'year': '2019', 'journal-title': 'Indian Pract.'}, { 'key': 'ref_21', 'doi-asserted-by': 'crossref', 'first-page': '117', 'DOI': '10.4291/wjgp.v8.i3.117', 'article-title': 'Oral spore-based probiotic supplementation was associated with reduced ' 'incidence of post-prandial dietary endotoxin, triglycerides, and ' 'disease risk biomarkers', 'volume': '8', 'author': 'McFarlin', 'year': '2017', 'journal-title': 'World J. Gastrointest Pathophysiol.'}, { 'key': 'ref_22', 'doi-asserted-by': 'crossref', 'first-page': '1307', 'DOI': '10.2217/fmb-2022-0066', 'article-title': 'Effects of combined prebiotic, probiotic, IgG and amino acid ' 'supplementation on the gut microbiome of patients with inflammatory ' 'bowel disease', 'volume': '17', 'author': 'Marzorati', 'year': '2022', 'journal-title': 'Future Microbiol.'}, { 'key': 'ref_23', 'doi-asserted-by': 'crossref', 'first-page': '110676', 'DOI': '10.1016/j.foodres.2021.110676', 'article-title': 'Treatment with a spore-based probiotic containing five strains of ' 'Bacillus induced changes in the metabolic activity and community ' 'composition of the gut microbiota in a SHIME(R) model of the human ' 'gastrointestinal system', 'volume': '149', 'author': 'Marzorati', 'year': '2021', 'journal-title': 'Food Res. Int.'}, { 'key': 'ref_24', 'doi-asserted-by': 'crossref', 'unstructured': 'Kalman, D.S., Schwartz, H.I., Alvarez, P., Feldman, S., Pezzullo, J.C., ' 'and Krieger, D.R. (2009). A prospective, randomized, double-blind, ' 'placebo-controlled parallel-group dual site trial to evaluate the ' 'effects of a Bacillus coagulans-based product on functional intestinal ' 'gas symptoms. BMC Gastroenterol., 9.', 'DOI': '10.1186/1471-230X-9-85'}, { 'key': 'ref_25', 'doi-asserted-by': 'crossref', 'first-page': '905', 'DOI': '10.1007/s10096-020-04138-6', 'article-title': 'COVID-19: Angiotensin-converting enzyme 2 (ACE2) expression and tissue ' 'susceptibility to SARS-CoV-2 infection', 'volume': '40', 'author': 'Beyerstedt', 'year': '2021', 'journal-title': 'Eur. J. Clin. Microbiol. Infect. Dis.'}, { 'key': 'ref_26', 'doi-asserted-by': 'crossref', 'first-page': '631', 'DOI': '10.1002/path.1570', 'article-title': 'Tissue distribution of ACE2 protein, the functional receptor for SARS ' 'coronavirus. A first step in understanding SARS pathogenesis', 'volume': '203', 'author': 'Hamming', 'year': '2004', 'journal-title': 'J. Pathol.'}, { 'key': 'ref_27', 'doi-asserted-by': 'crossref', 'unstructured': 'Tanikawa, T., Kiba, Y., Yu, J., Hsu, K., Chen, S., Ishii, A., Yokogawa, ' 'T., Suzuki, R., Inoue, Y., and Kitamura, M. (2022). Degradative Effect ' 'of Nattokinase on Spike Protein of SARS-CoV-2. Molecules, 27.', 'DOI': '10.3390/molecules27175405'}, { 'key': 'ref_28', 'doi-asserted-by': 'crossref', 'first-page': '21', 'DOI': '10.1016/j.bbrc.2021.07.034', 'article-title': 'Natto extract, a Japanese fermented soybean food, directly inhibits ' 'viral infections including SARS-CoV-2 in vitro', 'volume': '570', 'author': 'Oba', 'year': '2021', 'journal-title': 'Biochem. Biophys. Res. Commun.'}, { 'key': 'ref_29', 'doi-asserted-by': 'crossref', 'first-page': '782', 'DOI': '10.1001/jama.2020.12839', 'article-title': 'Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus ' 'Disease 2019 (COVID-19): A Review', 'volume': '324', 'author': 'Wiersinga', 'year': '2020', 'journal-title': 'JAMA'}, { 'key': 'ref_30', 'doi-asserted-by': 'crossref', 'first-page': '667', 'DOI': '10.1016/S2468-1253(20)30126-6', 'article-title': 'Manifestations and prognosis of gastrointestinal and liver involvement ' 'in patients with COVID-19: A systematic review and meta-analysis', 'volume': '5', 'author': 'Mao', 'year': '2020', 'journal-title': 'Lancet Gastroenterol. Hepatol.'}, { 'key': 'ref_31', 'doi-asserted-by': 'crossref', 'first-page': 'e0139621', 'DOI': '10.1128/JVI.01396-21', 'article-title': 'Direct Activation of Endothelial Cells by SARS-CoV-2 Nucleocapsid ' 'Protein Is Blocked by Simvastatin', 'volume': '95', 'author': 'Qian', 'year': '2021', 'journal-title': 'J. Virol.'}, { 'key': 'ref_32', 'doi-asserted-by': 'crossref', 'unstructured': 'Catinean, A., Neag, M.A., Krishnan, K., Muntean, D.M., Bocsan, C.I., ' 'Pop, R.M., Mitre, A.O., Melincovici, C.S., and Buzoianu, A.D. (2020). ' 'Probiotic Bacillus Spores Together with Amino Acids and Immunoglobulins ' 'Exert Protective Effects on a Rat Model of Ulcerative Colitis. ' 'Nutrients, 12.', 'DOI': '10.3390/nu12123607'}, { 'key': 'ref_33', 'doi-asserted-by': 'crossref', 'unstructured': 'El-Radhi, A.S. (2019). Clinical Manual of Fever in Children, Springer.', 'DOI': '10.1007/978-3-319-92336-9'}, { 'key': 'ref_34', 'doi-asserted-by': 'crossref', 'first-page': '296', 'DOI': '10.12998/wjcc.v9.i2.296', 'article-title': 'Effect of a fever in viral infections—The ‘Goldilocks’ phenomenon?', 'volume': '9', 'author': 'Belon', 'year': '2021', 'journal-title': 'World J. Clin. Cases'}, { 'key': 'ref_35', 'doi-asserted-by': 'crossref', 'first-page': '31', 'DOI': '10.1016/j.coviro.2016.01.001', 'article-title': 'Type I interferons in viral control and immune regulation', 'volume': '16', 'author': 'Teijaro', 'year': '2016', 'journal-title': 'Curr. Opin. Virol.'}, { 'key': 'ref_36', 'doi-asserted-by': 'crossref', 'first-page': '296', 'DOI': '10.1016/j.coviro.2013.05.019', 'article-title': 'Viral modulation of programmed necrosis', 'volume': '3', 'author': 'Kaiser', 'year': '2013', 'journal-title': 'Curr. Opin. Virol.'}, { 'key': 'ref_37', 'doi-asserted-by': 'crossref', 'first-page': '255', 'DOI': '10.1038/s41392-021-00679-0', 'article-title': 'The signal pathways and treatment of cytokine storm in COVID-19', 'volume': '6', 'author': 'Yang', 'year': '2021', 'journal-title': 'Signal Transduct. Target. Ther.'}, { 'key': 'ref_38', 'first-page': 'R269', 'article-title': 'Role of IL-6 and TNF in thermoregulation and survival during sepsis in ' 'mice', 'volume': '275', 'author': 'Leon', 'year': '1998', 'journal-title': 'Am. J. Physiol.'}, { 'key': 'ref_39', 'doi-asserted-by': 'crossref', 'first-page': '20', 'DOI': '10.3892/etm.2021.10942', 'article-title': 'Lactobacillus plantarum induces innate cytokine responses that ' 'potentially provide a protective benefit against COVID-19: A ' 'single-arm, double-blind, prospective trial combined with an in vitro ' 'cytokine response assay', 'volume': '23', 'author': 'Kageyama', 'year': '2022', 'journal-title': 'Exp. Ther. Med.'}, { 'key': 'ref_40', 'doi-asserted-by': 'crossref', 'first-page': '789242', 'DOI': '10.3389/fnut.2021.789242', 'article-title': 'Boosting Vaccine-Elicited Respiratory Mucosal and Systemic COVID-19 ' 'Immunity in Mice with the Oral Lactobacillus Plantarum', 'volume': '8', 'author': 'Xu', 'year': '2021', 'journal-title': 'Front. Nutr.'}, { 'key': 'ref_41', 'doi-asserted-by': 'crossref', 'first-page': '9', 'DOI': '10.1053/j.gastro.2021.09.009', 'article-title': 'Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?', 'volume': '162', 'author': 'Lau', 'year': '2022', 'journal-title': 'Gastroenterology'}, { 'key': 'ref_42', 'doi-asserted-by': 'crossref', 'first-page': '300', 'DOI': '10.1007/s13668-021-00375-z', 'article-title': 'Impact of COVID-19 on the Intestinal Microbiome', 'volume': '10', 'author': 'Sankararaman', 'year': '2021', 'journal-title': 'Curr. Nutr. Rep.'}, { 'key': 'ref_43', 'unstructured': '(2022, September 28). Probiotics in Food: Health and Nutritional ' 'Properties and Guidelines for Evaluation. Available online: ' 'https://www.fao.org/3/a0512e/a0512e.pdf.'}, { 'key': 'ref_44', 'doi-asserted-by': 'crossref', 'first-page': '2669', 'DOI': '10.1093/cid/ciaa709', 'article-title': 'Alterations of the Gut Microbiota in Patients with Coronavirus Disease ' '2019 or H1N1 Influenza', 'volume': '71', 'author': 'Gu', 'year': '2020', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': 'ref_45', 'doi-asserted-by': 'crossref', 'first-page': 'S150', 'DOI': '10.1513/AnnalsATS.201503-133AW', 'article-title': 'The Gut-Lung Axis in Respiratory Disease', 'volume': '12', 'author': 'Marsland', 'year': '2015', 'journal-title': 'Ann. Am. Thorac. Soc.'}, { 'key': 'ref_46', 'doi-asserted-by': 'crossref', 'first-page': '2754', 'DOI': '10.3389/fimmu.2019.02754', 'article-title': 'Immunomodulating Activity and Therapeutic Effects of Short Chain Fatty ' 'Acids and Tryptophan Post-Biotics in Inflammatory Bowel Disease', 'volume': '10', 'author': 'Russo', 'year': '2019', 'journal-title': 'Front. Immunol.'}, { 'key': 'ref_47', 'doi-asserted-by': 'crossref', 'first-page': '103293', 'DOI': '10.1016/j.ebiom.2021.103293', 'article-title': 'Short chain fatty acids and its producing organisms: An overlooked ' 'therapy for IBD?', 'volume': '66', 'author': 'Deleu', 'year': '2021', 'journal-title': 'EBioMedicine'}, { 'key': 'ref_48', 'doi-asserted-by': 'crossref', 'first-page': '928', 'DOI': '10.1016/j.cell.2017.01.022', 'article-title': 'Mining the Human Gut Microbiota for Immunomodulatory Organisms', 'volume': '168', 'author': 'Sefik', 'year': '2017', 'journal-title': 'Cell'}, { 'key': 'ref_49', 'doi-asserted-by': 'crossref', 'first-page': '289', 'DOI': '10.1006/biol.1997.0099', 'article-title': 'Mechanism of inactivation of enveloped viruses by the biosurfactant ' 'surfactin from Bacillus subtilis', 'volume': '25', 'author': 'Vollenbroich', 'year': '1997', 'journal-title': 'Biologicals'}, { 'key': 'ref_50', 'doi-asserted-by': 'crossref', 'first-page': '812', 'DOI': '10.1164/rccm.202005-1583OC', 'article-title': 'Characterization of the Inflammatory Response to Severe COVID-19 ' 'Illness', 'volume': '202', 'author': 'McElvaney', 'year': '2020', 'journal-title': 'Am. J. Respir. Crit. Care Med.'}, { 'key': 'ref_51', 'doi-asserted-by': 'crossref', 'first-page': '610300', 'DOI': '10.3389/fimmu.2020.610300', 'article-title': 'Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection ' 'of Asymptomatic, Mild, and Severe Cases', 'volume': '11', 'author': 'Carsetti', 'year': '2020', 'journal-title': 'Front. Immunol.'}, { 'key': 'ref_52', 'doi-asserted-by': 'crossref', 'first-page': '518', 'DOI': '10.1016/j.jaci.2020.07.001', 'article-title': 'The role of IL-6 and other mediators in the cytokine storm associated ' 'with SARS-CoV-2 infection', 'volume': '146', 'author': 'Copaescu', 'year': '2020', 'journal-title': 'J. Allergy Clin. Immunol.'}, { 'key': 'ref_53', 'doi-asserted-by': 'crossref', 'first-page': '261', 'DOI': '10.1111/imm.13223', 'article-title': 'Immunopathological characteristics of coronavirus disease 2019 cases in ' 'Guangzhou, China', 'volume': '160', 'author': 'Tan', 'year': '2020', 'journal-title': 'Immunology'}, { 'key': 'ref_54', 'doi-asserted-by': 'crossref', 'first-page': 'e4197', 'DOI': '10.1093/cid/ciaa851', 'article-title': 'Impact of Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load on ' 'Risk of Intubation and Mortality among Hospitalized Patients with ' 'Coronavirus Disease 2019', 'volume': '73', 'author': 'Magleby', 'year': '2021', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': 'ref_55', 'doi-asserted-by': 'crossref', 'first-page': '395', 'DOI': '10.1038/nrd.2018.45', 'article-title': 'Interleukin-6: Designing specific therapeutics for a complex cytokine', 'volume': '17', 'author': 'Garbers', 'year': '2018', 'journal-title': 'Nat. Rev. Drug Discov.'}, { 'key': 'ref_56', 'first-page': '753', 'article-title': 'Origin, transmission, diagnosis and management of coronavirus disease ' '2019 (COVID-19)', 'volume': '96', 'author': 'Umakanthan', 'year': '2020', 'journal-title': 'Postgrad. Med. J.'}], 'container-title': 'Nutrients', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/2072-6643/15/3/488/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 1, 18]], 'date-time': '2023-01-18T07:56:49Z', 'timestamp': 1674028609000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/2072-6643/15/3/488'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 1, 17]]}, 'references-count': 56, 'journal-issue': {'issue': '3', 'published-online': {'date-parts': [[2023, 2]]}}, 'alternative-id': ['nu15030488'], 'URL': 'http://dx.doi.org/10.3390/nu15030488', 'relation': {}, 'ISSN': ['2072-6643'], 'subject': ['Food Science', 'Nutrition and Dietetics'], 'container-title-short': 'Nutrients', 'published': {'date-parts': [[2023, 1, 17]]}}