{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:30:40Z","timestamp":1761845440525,"version":"3.41.2"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>A binary model for the classification of chronic diseases has formerly been proposed. The model classifies chronic diseases as \u201chigh Treg\u201d or \u201clow Treg\u201d diseases according to the extent of regulatory T cells (Treg) activity (frequency or function) observed. The present paper applies this model to severe acute respiratory syndrome coronavirus 2 (SARS<jats:italic>-<\/jats:italic>CoV<jats:italic>-<\/jats:italic>2) infection. The model correctly predicts the efficacy or inefficacy of several immune-modulating drugs in the treatment of severe coronavirus disease 2019 (COVID-19) disease. It also correctly predicts the class of pathogens mostly associated with SARS-CoV-2 infection. The clinical implications are the following: (a) any search for new immune-modulating drugs for the treatment of COVID-19 should exclude candidates that do not induce \u201chigh Treg\u201d immune reaction or those that do not spare CD8+ T cells; (b) immune-modulating drugs, which are effective against SARS-CoV-2, may not be effective against any variant of the virus that does not induce \u201clow Treg\u201d reaction; (c) any immune-modulating drug, which is effective in treating COVID-19, will also alleviate most coinfections; and (d) severe COVID-19 patients should avoid contact with carriers of \u201clow Treg\u201d pathogens.<\/jats:p>","DOI":"10.3389\/fimmu.2021.716084","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T10:40:36Z","timestamp":1630752036000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["The Binary Model of Chronic Diseases Applied to COVID-19"],"prefix":"10.3389","volume":"12","author":[{"given":"Zeev","family":"Elkoshi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S227279","article-title":"The Binary Classification of Chronic Diseases","volume":"12","author":"Elkoshi","year":"2019","journal-title":"J Inflamm Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S249384","article-title":"\u201cHigh Treg\u201d Inflammations Promote (Most) Non-Hematologic Cancers While \u201cLow Treg\u201d Inflammations Promote Lymphoid Cancers","volume":"13","author":"Elkoshi","year":"2020","journal-title":"J\u00a0Inflamm Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e137799","DOI":"10.1172\/jci.insight.137799","article-title":"The Laboratory Tests and Host Immunity of COVID-19 Patients With Different Severity of Illness","volume":"5","author":"Wang","year":"2020","journal-title":"JCI Insight"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"Clin Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI137244","article-title":"Clinical and Immunological Features of Severe and Moderate Coronavirus Disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J\u00a0Clin Invest"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0447-2","article-title":"High-Dimensional Immune Profiling by Mass Cytometry Revealed Immunosuppression and Dysfunction of Immunity in COVID-19 Patients","volume":"17","author":"Wang","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/08830185.2021.1883600","article-title":"COVID-19: Immunology, Immunopathogenesis and Potential Therapies [Published Online Ahead of Print, 2021 Feb 27]","author":"Bhardwaj","year":"2021","journal-title":"Int Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.08.010","article-title":"Cirrhosis-Associated Immune Dysfunction: Distinctive Features and Clinical Relevance","volume":"61","author":"Albillos","year":"2014","journal-title":"J Hepatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.013","article-title":"COVID-19 Makes B Cells Forget, But T Cells Remember","volume":"183","author":"Ca\u00f1ete","year":"2020","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2020.102437","article-title":"Increased Expression of CD8 Marker on T-Cells in COVID-19 Patients","volume":"83","author":"Ganji","year":"2020","journal-title":"Blood Cells Mol Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.009","article-title":"Host Defense Pathways: Role of Redundancy and Compensation in Infectious Disease Phenotypes","volume":"34","author":"Nish","year":"2011","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-162289\/v1","article-title":"CD8 T Cells Compensate for Impaired Humoral Immunity in COVID-19 Patients With Hematologic Cancer","author":"Huang","year":""},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.03.013","article-title":"Systematic Evaluation of 640 FDA Drugs for Their Effect on CD4+Foxp3+ Regulatory T Cells Using a Novel Cell-Based High Throughput Screening Assay","volume":"85","author":"Mao","year":"2013","journal-title":"Biochem Pharmacol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.03.004","article-title":"GILZ Promotes Production of Peripherally Induced Treg Cells and Mediates the Crosstalk Between Glucocorticoids and TGF-B Signaling","volume":"7","author":"Bereshchenko","year":"2014","journal-title":"Cell Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.jaci.2008.01.035","article-title":"Corticosteroids Enhance CD8+ T Cell-Mediated Airway Hyperresponsiveness and Allergic Inflammation by Upregulating Leukotriene B4 Receptor 1","volume":"121","author":"Ohnishi","year":"2008","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01521","article-title":"Divergent Effects of a Transient Corticosteroid Therapy on Virus-Specific Quiescent and Effector CD8+ T Cells","volume":"10","author":"Kumar","year":"2019","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190738","article-title":"Selective Inhibition of Low-Affinity Memory CD8+ T Cells by Corticosteroids","volume":"216","author":"Tokunaga","year":"2019","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S303750","article-title":"The Binary Classification of Protein Kinases","volume":"14","author":"Elkoshi","year":"2021","journal-title":"J Inflamm Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket466","article-title":"Effects of Tofacitinib on Lymphocytes in Rheumatoid Arthritis: Relation to Efficacy and Infectious Adverse Events","volume":"53","author":"Sonomoto","year":"2014","journal-title":"Rheumatol (Oxford)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141772","article-title":"Baricitinib Restrains the Immune Dysregulation in Patients With Severe COVID-19","volume":"130","author":"Bronte","year":"2020","journal-title":"J\u00a0Clin Invest"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000761","article-title":"Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis","volume":"134","author":"Albeituni","year":"2019","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-484642","article-title":"The JAK-Inhibitor Ruxolitinib Impairs Dendritic Cell Function In Vitro and In Vivo","volume":"122","author":"Heine","year":"2013","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.12.8338","article-title":"Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients","volume":"177","author":"Battaglia","year":"2006","journal-title":"J\u00a0Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.jaci.2019.11.043","article-title":"Treatment With Rapamycin can Restore Regulatory T-Cell Function in IPEX Patients","volume":"145","author":"Passerini","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00898.x","article-title":"The Role of mTOR in Memory CD8 T-Cell Differentiation","volume":"235","author":"Araki","year":"2010","journal-title":"Immunol Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nature08155","article-title":"mTOR Regulates Memory CD8 T-Cell Differentiation","volume":"460","author":"Araki","year":"2009","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nature08097","article-title":"Enhancing CD8 T-Cell Memory by Modulating Fatty Acid Metabolism","volume":"460","author":"Pearce","year":"2009","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.01.001","article-title":"Rapamycin: One Drug, Many Effects","volume":"19","author":"Li","year":"2014","journal-title":"Cell Metab"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1811892115","article-title":"mTOR Inhibitors Lower an Intrinsic Barrier to Virus Infection Mediated by IFITM3","volume":"115","author":"Shi","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2010.03269.x","article-title":"Simvastatin Induces Foxp3+ T Regulatory Cells by Modulation of Transforming Growth Factor-Beta Signal Transduction","volume":"130","author":"Kim","year":"2010","journal-title":"Immunology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/762506","article-title":"Statins Increase the Frequency of Circulating CD4+ FOXP3+ Regulatory T Cells in Healthy Individuals","volume":"2015","author":"Rodr\u00edguez-Perea","year":"2015","journal-title":"J Immunol Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/167086","article-title":"Statins as Modulators of Regulatory T-Cell Biology","volume":"2013","author":"Forero-Pe\u00f1a","year":"2013","journal-title":"Mediators Inflamm"},{"key":"B33","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.cmet.2019.04.002","article-title":"Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment","volume":"30","author":"Ma","year":"2019","journal-title":"Cell Metab"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-018-8994-7","article-title":"Effects of Simvastatin on the Function of Splenic CD4+ and CD8+ T Cells in Sepsis Mice","volume":"66","author":"Kong","year":"2018","journal-title":"Immunol Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3181fb0486","article-title":"Lovastatin Inhibits T-Cell Proliferation While Preserving the Cytolytic Function of EBV, CMV, and MART-1-Specific CTLs","volume":"33","author":"Li","year":"2010","journal-title":"J Immunother"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000475","article-title":"Effects of Atorvastatin and Pravastatin on Immune Activation and T-Cell Function in Antiretroviral Therapy-Suppressed HIV-1-Infected Patients","volume":"28","author":"Overton","year":"2014","journal-title":"AIDS"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7619849","article-title":"Fluvastatin-Pretreated Donor Cells Attenuated Murine aGVHD by Balancing Effector T Cell Distribution and Function Under the Regulation of KLF2","volume":"2020","author":"Zhao","year":"2020","journal-title":"BioMed Res Int"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e131530","DOI":"10.1172\/jci.insight.131530","article-title":"Effects of Rosuvastatin on the Immune System in Healthy Volunteers With Normal Serum Cholesterol","volume":"4","author":"Karmaus","year":"2019","journal-title":"JCI Insight"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000879","article-title":"IMEA 043-CESAR Trial Working Group. Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy","volume":"71","author":"Weiss","year":"2016","journal-title":"J Acquir Immune Defic Syndr"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2020.101054","article-title":"Antiviral Effects of Statins","volume":"79","author":"Gorabi","year":"2020","journal-title":"Prog Lipid Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1101\/2020.07.13.20152272","article-title":"Effect of Statins on SARS-CoV-2 Infection","author":"Moeller","year":"2020","journal-title":"medRxiv"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1992.tb05773.x","article-title":"Pharmacokinetics of Fluvastatin After Single and Multiple Doses in Normal Volunteers","volume":"32","author":"Tse","year":"1992","journal-title":"J Clin Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2020.158849","article-title":"Cholesterol, Lipoproteins, and COVID-19: Basic Concepts and Clinical Applications","volume":"1866","author":"Ko\u010dar","year":"2021","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1177\/000456329703400308","article-title":"Effect of Simvastatin Therapy on Cell Membrane Cholesterol Content and Membrane Function as Assessed by Polymorphonuclear Cell NADPH Oxidase Activity","volume":"34","author":"Day","year":"1997","journal-title":"Ann Clin Biochem"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.05.046","article-title":"Co-Infections in People With COVID-19: A Systematic Review and Meta-Analysis","volume":"81","author":"Lansbury","year":"2020","journal-title":"J Infect"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2015.12.006","article-title":"Imbalance of Peripheral Blood Th17 and Treg Responses in Children With Refractory Mycoplasma Pneumoniae Pneumonia","volume":"22","author":"Guo","year":"2016","journal-title":"J Infect Chemother"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2011-200160","article-title":"Combined Haemophilus Influenzae Respiratory Infection and Allergic Airways Disease Drives Chronic Infection and Features of Neutrophilic Asthma","volume":"67","author":"Essilfie","year":"2012","journal-title":"Thorax"},{"key":"B48","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.immuni.2011.10.018","article-title":"Th17 Cells Mediate Clade-Specific, Serotype-Independent Mucosal Immunity","volume":"35","author":"Chen","year":"2011","journal-title":"Immunity"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9834020","article-title":"Acinetobacter Baumannii Infection and IL-17 Mediated Immunity","volume":"2016","author":"Yan","year":"2016","journal-title":"Mediators Inflamm"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808353115","article-title":"Protective Immunity in Recurrent\u00a0Staphylococcus Aureus Infection Reflects Localized Immune Signatures and Macrophage-Conferred Memory","volume":"115","author":"Chan","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2012.1010","article-title":"Oral Administration of Enterococcus Faecalis FK-23 Suppresses Th17 Cell Development and Attenuates Allergic Airway Responses in Mice","volume":"30","author":"Zhang","year":"2012","journal-title":"Int J Mol Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.immuni.2011.10.018","article-title":"Th17 Cells Mediate Clade-Specific, Serotype-Independent Mucosal Immunity","volume":"35","author":"Chen","year":"2011","journal-title":"Immunity"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.17","article-title":"Regulatory T Cells Promote a Protective Th17-Associated Immune Response to Intestinal Bacterial Infection With C. Rodentium","volume":"7","author":"Wang","year":"2014","journal-title":"Mucosal Immunol"},{"key":"B54","article-title":"The Changes of Th17\/Treg and Related Cytokines: IL-17, IL-23, IL-10, and TGF-\u03b2 in Respiratory Syncytial Virus Bronchiolitis Rat Model","volume":"16","author":"Gao","year":"2017","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"R201","DOI":"10.1186\/cc8208","article-title":"Th1 and Th17 Hypercytokinemia as Early Host Response Signature in Severe Pandemic Influenza","volume":"13","author":"Bermejo-Martin","year":"2009","journal-title":"Crit Care"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.23254","article-title":"Increased Frequency of Th17 Cells in the Peripheral Blood of Children Infected With Enterovirus 71","volume":"84","author":"Chen","year":"2012","journal-title":"J Med Virol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25406","article-title":"Th17 Serum Cytokines in Relation to Laboratory-Confirmed Respiratory Viral Infection: A Pilot Study","volume":"91","author":"Antalis","year":"2019","journal-title":"J Med Virol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2019:6491738","DOI":"10.1155\/2019\/6491738","article-title":"Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development","volume":"7","author":"Mubarak","year":"2019","journal-title":"J Immunol Res"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.04.008","article-title":"IL-17 Contributes to Neutrophil Recruitment But Not to Control of Viral Replication During Acute Mouse Adenovirus Type 1 Respiratory Infection","author":"McCarthy","year":"2014","journal-title":"Virology"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.5415\/apallergy.2017.7.4.206","article-title":"Comparison of Nasal Cytokine Profiles of Human Metapneumovirus and Respiratory Syncytial Virus","volume":"7","author":"Park","year":"2017","journal-title":"Asia Pac Allergy"},{"key":"B61","article-title":"Role of Treg\/Th17 Balance in the Pathogenesis of Cytomegalovirus Infection","volume":"28","author":"Tan","year":"2012","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00171","article-title":"Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients With Acute Viral Myocarditis","volume":"6","author":"Long","year":"2016","journal-title":"Front Cell Infect Microbiol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02243-20","article-title":"Impaired Cytotoxic Cd8+\u00a0T Cell Response in Elderly COVID-19 Patients","volume":"11","author":"Westmeier","year":"2020","journal-title":"mBio"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0782-6","article-title":"Broad and Strong Memory CD4+\u00a0and Cd8+\u00a0T Cells Induced by SARS-CoV-2 in UK Convalescent Individuals Following COVID-19","volume":"21","author":"Peng","year":"2020","journal-title":"Nat Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01505-14","article-title":"Virus-Specific Memory CD8 T Cells Provide Substantial Protection From Lethal Severe Acute Respiratory Syndrome Coronavirus Infection","volume":"88","author":"Channappanavar","year":"2014","journal-title":"J Virol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1056\/NEJMoa2021436","article-title":"Dexamethasone in Hospitalized Patients With Covid-19","volume":"384","author":"Horby","year":"2021","journal-title":"N Engl J Med"},{"volume-title":"Corticosteroids for COVID-19: Living Guidance","year":"2020","key":"B67"},{"key":"B68","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12879-020-05730-z","article-title":"JAK-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-Analysis","volume":"21","author":"Walz","year":"2021","journal-title":"BMC Infect Dis"},{"key":"B69","unstructured":"Novartis Provides Update on RUXCOVID Study of Ruxolitinib for Hospitalized Patients With COVID-192020"},{"key":"B70","unstructured":"Incyte Announces Results From the Phase 3 DEVENT Study Evaluating Ruxolitinib (Jakafi\u00ae) as a Treatment for Patients With COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS) on Mechanical Ventilation"},{"key":"B71","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1056\/NEJMoa2031994","article-title":"ACTT-2 Study Group Members. Baricitinib Plus Remdesivir for Hospitalized Adults With Covid-19","volume":"384","author":"Kalil","year":"2021","journal-title":"N Engl J Med"},{"key":"B72","doi-asserted-by":"publisher","first-page":"2021.04.30.21255934","DOI":"10.1101\/2021.04.30.21255934","article-title":"Baricitinib Plus Standard of Care for Hospitalized Adults With COVID-19","author":"Marconi","year":"2021","journal-title":"medRxv"},{"key":"B73","unstructured":"Letter to Eli Lilly and Company (July 28, 2021)"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101643","article-title":"Tofacitinib in Patients Hospitalized With Covid-19 Pneumonia","volume":"385","author":"Guimar\u00e3es","year":"2021","journal-title":"N Engl J Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-020-02504-y","article-title":"Protective Role of Statins in COVID 19 Patients: Importance of Pharmacokinetic Characteristics Rather Than Intensity of Action","volume":"15","author":"Rossi","year":"2020","journal-title":"Intern Emerg Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.716084\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T10:40:43Z","timestamp":1630752043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.716084\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,3]]},"references-count":75,"alternative-id":["10.3389\/fimmu.2021.716084"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.716084","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2021,9,3]]},"article-number":"716084"}}