{"id":"https://openalex.org/W3172336804","doi":"https://doi.org/10.1016/j.jiph.2021.06.004","title":"Interleukin-6 (IL-6) inhibitors as therapeutic agents for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis","display_name":"Interleukin-6 (IL-6) inhibitors as therapeutic agents for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis","publication_year":2021,"publication_date":"2021-06-15","ids":{"openalex":"https://openalex.org/W3172336804","doi":"https://doi.org/10.1016/j.jiph.2021.06.004","mag":"3172336804","pmid":"https://pubmed.ncbi.nlm.nih.gov/34153723","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/8204364"},"language":"en","primary_location":{"id":"doi:10.1016/j.jiph.2021.06.004","doi":"https://doi.org/10.1016/j.jiph.2021.06.004","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jiph.2021.06.004","pdf_url":"https://www.sciencedirect.com/science/article/pii/S1876034121001593/pdf","source":{"id":"https://openalex.org/S53706017","display_name":"Journal of Infection and Public Health","issn_l":"1876-0341","issn":["1876-0341","1876-035X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-70"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Infection and Public Health","raw_type":"journal-article"},"volume":null,"type":"review","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.sciencedirect.com/science/article/pii/S1876034121001593/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5066884259","display_name":"Rizaldy Taslim Pinzon","orcid":"https://orcid.org/0000-0002-3357-9907","observed_orcids":["https://orcid.org/0000-0002-3357-9907"]},"institutions":[{"id":"https://openalex.org/I146112026","display_name":"Duta Wacana Christian University","ror":"https://ror.org/036agwg70","country_code":"ID","type":"education","lineage":["https://openalex.org/I146112026"]}],"countries":["ID"],"is_corresponding":true,"raw_author_name":"Rizaldy Taslim Pinzon","raw_affiliation_strings":["Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia. Electronic address: drpinzon17@gmail.com","Bethesda Hospital, Yogyakarta, Indonesia","Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia. Electronic address: drpinzon17@gmail.com","institution_ids":["https://openalex.org/I146112026"]},{"raw_affiliation_string":"Bethesda Hospital, Yogyakarta, Indonesia","institution_ids":[]},{"raw_affiliation_string":"Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia","institution_ids":["https://openalex.org/I146112026"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063459254","display_name":"Vincent Ongko Wijaya","orcid":"https://orcid.org/0000-0001-7147-851X","observed_orcids":["https://orcid.org/0000-0001-7147-851X"]},"institutions":[{"id":"https://openalex.org/I146112026","display_name":"Duta Wacana Christian University","ror":"https://ror.org/036agwg70","country_code":"ID","type":"education","lineage":["https://openalex.org/I146112026"]}],"countries":["ID"],"is_corresponding":false,"raw_author_name":"Vincent Ongko Wijaya","raw_affiliation_strings":["Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia","Bethesda Hospital, Yogyakarta, Indonesia","Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia"],"raw_orcid":"https://orcid.org/0000-0001-7147-851X","affiliations":[{"raw_affiliation_string":"Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia","institution_ids":["https://openalex.org/I146112026"]},{"raw_affiliation_string":"Bethesda Hospital, Yogyakarta, Indonesia","institution_ids":[]},{"raw_affiliation_string":"Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia","institution_ids":["https://openalex.org/I146112026"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5002292906","display_name":"Ranbebasa Bijak Buana","orcid":"https://orcid.org/0000-0002-2630-9415","observed_orcids":["https://orcid.org/0000-0002-2630-9415"]},"institutions":[{"id":"https://openalex.org/I146112026","display_name":"Duta Wacana Christian University","ror":"https://ror.org/036agwg70","country_code":"ID","type":"education","lineage":["https://openalex.org/I146112026"]}],"countries":["ID"],"is_corresponding":false,"raw_author_name":"Ranbebasa Bijak Buana","raw_affiliation_strings":["Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia","Bethesda Hospital, Yogyakarta, Indonesia","Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia"],"raw_orcid":"https://orcid.org/0000-0002-2630-9415","affiliations":[{"raw_affiliation_string":"Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia; Bethesda Hospital, Yogyakarta, Indonesia","institution_ids":["https://openalex.org/I146112026"]},{"raw_affiliation_string":"Bethesda Hospital, Yogyakarta, Indonesia","institution_ids":[]},{"raw_affiliation_string":"Faculty of Medicine, Duta Wacana Christian University, Yogyakarta, Indonesia","institution_ids":["https://openalex.org/I146112026"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5066884259"],"corresponding_institution_ids":["https://openalex.org/I146112026"],"apc_list":{"value":1250,"currency":"USD","value_usd":1250},"apc_paid":{"value":1250,"currency":"USD","value_usd":1250},"fwci":0.9073,"has_fulltext":true,"cited_by_count":36,"citation_normalized_percentile":{"value":0.70148462,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":95,"max":99},"biblio":{"volume":"14","issue":"8","first_page":"1001","last_page":"1009"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10041","display_name":"COVID-19 Clinical Research Studies","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10041","display_name":"COVID-19 Clinical Research Studies","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10118","display_name":"SARS-CoV-2 and COVID-19 Research","score":0.00039999998989515007,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10322","display_name":"Respiratory Support and Mechanisms","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/il-6-inhibitors","display_name":"IL-6 inhibitors","score":0.9160000085830688},{"id":"https://openalex.org/keywords/covid-19","display_name":"COVID-19 pandemic","score":0.9959999918937683},{"id":"https://openalex.org/keywords/tocilizumab","display_name":"tocilizumab","score":0.996999979019165},{"id":"https://openalex.org/keywords/sarilumab","display_name":"sarilumab","score":1.0},{"id":"https://openalex.org/keywords/mortality","display_name":"mortality","score":0.6840000152587891},{"id":"https://openalex.org/keywords/cytokine-storm","display_name":"cytokine storm","score":0.7749999761581421},{"id":"https://openalex.org/keywords/mechanical-ventilation","display_name":"mechanical ventilation","score":0.7839999794960022},{"id":"https://openalex.org/keywords/length-of-hospital-stay","display_name":"length of hospital stay","score":0.8619999885559082},{"id":"https://openalex.org/keywords/hospital-discharge","display_name":"hospital discharge","score":0.703000009059906},{"id":"https://openalex.org/keywords/severe-covid-19-treatment","display_name":"severe COVID-19 treatment","score":0.7910000085830688}],"concepts":[{"id":"https://openalex.org/C2777178219","wikidata":"https://www.wikidata.org/wiki/Q425154","display_name":"Tocilizumab","level":3,"score":0.9113450050354004},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.8618637323379517},{"id":"https://openalex.org/C95190672","wikidata":"https://www.wikidata.org/wiki/Q815382","display_name":"Meta-analysis","level":2,"score":0.7711982727050781},{"id":"https://openalex.org/C3008058167","wikidata":"https://www.wikidata.org/wiki/Q84263196","display_name":"Coronavirus disease 2019 (COVID-19)","level":4,"score":0.6075847148895264},{"id":"https://openalex.org/C2777080012","wikidata":"https://www.wikidata.org/wiki/Q3766250","display_name":"Mechanical ventilation","level":2,"score":0.5300493240356445},{"id":"https://openalex.org/C82789193","wikidata":"https://www.wikidata.org/wiki/Q2142611","display_name":"Relative risk","level":3,"score":0.5044270753860474},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4976101219654083},{"id":"https://openalex.org/C11988809","wikidata":"https://www.wikidata.org/wiki/Q412889","display_name":"Interleukin 6","level":3,"score":0.43225765228271484},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.3963729739189148},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.33061155676841736},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.32077479362487793},{"id":"https://openalex.org/C44249647","wikidata":"https://www.wikidata.org/wiki/Q208498","display_name":"Confidence interval","level":2,"score":0.28382402658462524},{"id":"https://openalex.org/C524204448","wikidata":"https://www.wikidata.org/wiki/Q788926","display_name":"Infectious disease (medical specialty)","level":3,"score":0.15165740251541138}],"mesh":[{"descriptor_ui":"D000086382","descriptor_name":"COVID-19","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000086402","descriptor_name":"SARS-CoV-2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012121","descriptor_name":"Respiration, Artificial","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015850","descriptor_name":"Interleukin-6","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016896","descriptor_name":"Treatment Outcome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1016/j.jiph.2021.06.004","doi":"https://doi.org/10.1016/j.jiph.2021.06.004","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jiph.2021.06.004","pdf_url":"https://www.sciencedirect.com/science/article/pii/S1876034121001593/pdf","source":{"id":"https://openalex.org/S53706017","display_name":"Journal of Infection and Public Health","issn_l":"1876-0341","issn":["1876-0341","1876-035X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-70"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Infection and Public Health","raw_type":"journal-article"},{"id":"pmid:34153723","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/34153723","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of infection and public health","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8204364","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8204364/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"J Infect Public Health","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:79811e00764546949fe47132917caa68","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/79811e00764546949fe47132917caa68","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Journal of Infection and Public Health, Vol 14, Iss 8, Pp 1001-1009 (2021)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.1016/j.jiph.2021.06.004","doi":"https://doi.org/10.1016/j.jiph.2021.06.004","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jiph.2021.06.004","pdf_url":"https://www.sciencedirect.com/science/article/pii/S1876034121001593/pdf","source":{"id":"https://openalex.org/S53706017","display_name":"Journal of Infection and Public Health","issn_l":"1876-0341","issn":["1876-0341","1876-035X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-70"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Infection and Public Health","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[{"display_name":"Systematic Review","id":"https://openalex.org/study-designs/systematic-review"},{"display_name":"Meta-Analysis","id":"https://openalex.org/study-designs/meta-analysis"}],"awards":[],"funders":[],"has_content":{"grobid_xml":true,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W3172336804.pdf","grobid_xml":"https://content.openalex.org/works/W3172336804.grobid-xml"},"referenced_works_count":49,"referenced_works":["https://openalex.org/W246286872","https://openalex.org/W2098923148","https://openalex.org/W2156098321","https://openalex.org/W2588681363","https://openalex.org/W2991792334","https://openalex.org/W3010956505","https://openalex.org/W3012421327","https://openalex.org/W3014050022","https://openalex.org/W3014663601","https://openalex.org/W3016661132","https://openalex.org/W3018269482","https://openalex.org/W3021343000","https://openalex.org/W3022970339","https://openalex.org/W3024776685","https://openalex.org/W3025160648","https://openalex.org/W3026301261","https://openalex.org/W3033591380","https://openalex.org/W3034882684","https://openalex.org/W3036229308","https://openalex.org/W3036398841","https://openalex.org/W3036430736","https://openalex.org/W3038241707","https://openalex.org/W3041464116","https://openalex.org/W3042042989","https://openalex.org/W3042405664","https://openalex.org/W3043104506","https://openalex.org/W3044965497","https://openalex.org/W3046371784","https://openalex.org/W3046740571","https://openalex.org/W3048457756","https://openalex.org/W3048601848","https://openalex.org/W3081462415","https://openalex.org/W3088294971","https://openalex.org/W3092004162","https://openalex.org/W3093604087","https://openalex.org/W3097548228","https://openalex.org/W3108032435","https://openalex.org/W3109543290","https://openalex.org/W3118570220","https://openalex.org/W3127354997","https://openalex.org/W3144149667","https://openalex.org/W3165022701","https://openalex.org/W4294215472","https://openalex.org/W6779986324","https://openalex.org/W6783104614","https://openalex.org/W6783778983","https://openalex.org/W6786109007","https://openalex.org/W6786939129","https://openalex.org/W6787925505"],"related_works":["https://openalex.org/W6940260364","https://openalex.org/W4206191947","https://openalex.org/W4224097043","https://openalex.org/W3137252557","https://openalex.org/W4299806176","https://openalex.org/W3097548228","https://openalex.org/W3214919148","https://openalex.org/W4394400278","https://openalex.org/W4205893356","https://openalex.org/W3163235237"],"abstract_inverted_index":{"INTRODUCTION:":[0],"Preliminary":[1],"studies":[2,74,123,138,144],"showed":[3],"that":[4,208],"coronavirus":[5],"disease":[6],"2019":[7],"(COVID-19)":[8],"disrupts":[9],"body":[10],"immune":[11],"system,":[12],"including":[13,162],"dysregulation":[14],"of":[15,56,63,102,111,127,142,172,197,215],"cytokine":[16],"interleukin-6":[17],"(IL-6).":[18],"IL-6":[19,57,198,209],"inhibitors":[20],"agents":[21,35,59,200,211],"have":[22],"been":[23],"used":[24,135],"as":[25,33],"treatment":[26,62],"options":[27],"for":[28,60,86,106,185,228,234],"COVID-19,":[29,218],"yet":[30],"their":[31],"benefit":[32],"therapeutic":[34,54],"remains":[36],"unclear.":[37],"OBJECTIVE:":[38],"We":[39,120],"performed":[40],"a":[41,125],"systematic":[42],"review":[43],"and":[44,70,84,104,152,232],"meta-analysis":[45],"to":[46,181,202],"synthesize":[47],"the":[48,52,61,72,87,99,132,137,213],"available":[49,76],"evidence":[50,206],"on":[51],"potential":[53],"effect":[55],"inhibitor":[58,199,210],"COVID-19.":[64,235],"METHODS:":[65],"Two":[66],"authors":[67],"initially":[68],"screened":[69],"reviewed":[71,121],"relevant":[73],"from":[75,98],"databases.":[77],"The":[78,89,109],"data":[79],"extracted":[80],"will":[81],"be":[82],"tabulated":[83],"analyzed":[85],"outcomes.":[88],"primary":[90],"outcome":[91],"was":[92,114,131],"mortality.":[93],"Secondary":[94],"outcomes":[95,161],"included":[96,143],"discharge":[97,164],"hospital,":[100],"length":[101,171],"stay,":[103],"requirement":[105,184],"mechanical":[107,186],"ventilation.":[108],"quality":[110],"each":[112],"study":[113],"assessed":[115],"using":[116],"OCEBM":[117],"ratings.":[118],"RESULTS:":[119],"18":[122],"with":[124,150],"total":[126],"3303":[128],"subjects.":[129],"Tocilizumab":[130],"most":[133],"commonly":[134],"in":[136,148,217,220],"(15":[139],"studies).":[140],"Meta-analysis":[141],"revealed":[145,194],"significant":[146],"reduction":[147],"mortality":[149,216],"tocilizumab":[151],"sarilumab":[153],"(RR":[154,165,188],"=":[155,166,189],"0.61,":[156],"95%":[157,168,178,191],"CI":[158,169,179,192],"0.49-0.76).":[159],"Other":[160],"hospital":[163],"1.04,":[167],"0.86-1.24),":[170],"stay":[173],"(mean":[174],"difference":[175],"-1.96":[176],"days,":[177],"-4.24":[180],"0.33)":[182],"or":[183],"ventilation":[187],"0.68,":[190],"0.32-1.45)":[193],"no":[195],"differences":[196],"compared":[201],"controls.":[203],"CONCLUSIONS:":[204],"Available":[205],"suggests":[207],"reduce":[212],"risk":[214],"especially":[219],"severe":[221],"conditions.":[222],"Further":[223],"well-designed":[224],"trials":[225],"are":[226],"needed":[227],"assessing":[229],"its":[230],"efficacy":[231],"safety":[233]},"counts_by_year":[{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":3},{"year":2023,"cited_by_count":7},{"year":2022,"cited_by_count":14},{"year":2021,"cited_by_count":8}],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2021-06-22T00:00:00"}