{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:45:37Z","timestamp":1794012337325,"version":"4.8.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Microbes and Infection"],"published-print":{"date-parts":[[2023,5]]},"DOI":"10.1016\/j.micinf.2022.105081","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T02:20:28Z","timestamp":1670379628000},"page":"105081","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"title":["Association of complement pathways with COVID-19 severity and outcomes"],"prefix":"10.1016","volume":"25","author":[{"given":"Kishor","family":"Devalaraja-Narashimha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-5731","authenticated-orcid":false,"given":"Peter J.","family":"Ehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1436-3366","authenticated-orcid":false,"given":"Matthew F.","family":"Wipperman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-903X","authenticated-orcid":false,"given":"Theodore","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1674-2001","authenticated-orcid":false,"given":"Chien","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6815-6023","authenticated-orcid":false,"given":"Simisola","family":"Afolayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Glass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Mellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George D.","family":"Yancopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer D.","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8380-1572","authenticated-orcid":false,"given":"Scott","family":"MacDonnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-2302","authenticated-orcid":false,"given":"Sara C.","family":"Hamon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Boyapati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.micinf.2022.105081_bib1","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical characteristics of coronavirus disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.micinf.2022.105081_bib2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.micinf.2022.105081_bib3","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced host response to SARS-CoV-2 drives development of COVID-19","volume":"181","author":"Blanco-Melo","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.micinf.2022.105081_bib4","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1136\/thoraxjnl-2020-216243","article-title":"COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms","volume":"76","author":"Loo","year":"2021","journal-title":"Thorax"},{"key":"10.1016\/j.micinf.2022.105081_bib5","doi-asserted-by":"crossref","first-page":"e01753","DOI":"10.1128\/mBio.01753-18","article-title":"Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis","volume":"9","author":"Gralinski","year":"2018","journal-title":"mBio"},{"key":"10.1016\/j.micinf.2022.105081_bib6","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.140711","article-title":"The complement system in COVID-19: friend and foe?","volume":"5","author":"Java","year":"2020","journal-title":"JCI Insight"},{"key":"10.1016\/j.micinf.2022.105081_bib7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/s41426-018-0063-8","article-title":"Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV","volume":"7","author":"Jiang","year":"2018","journal-title":"Emerg Microb Infect"},{"key":"10.1016\/j.micinf.2022.105081_bib8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41581-020-00357-4","article-title":"Immunity, endothelial injury and complement-induced coagulopathy in COVID-19","volume":"17","author":"Perico","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.micinf.2022.105081_bib9","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fimmu.2015.00262","article-title":"Complement system part I - molecular mechanisms of activation and regulation","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"10.1016\/j.micinf.2022.105081_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2020.04.007","article-title":"Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases","volume":"220","author":"Magro","year":"2020","journal-title":"Transl Res"},{"key":"10.1016\/j.micinf.2022.105081_bib11","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/jth.14768","article-title":"Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia","volume":"18","author":"Tang","year":"2020","journal-title":"J\u00a0Thromb Haemostasis"},{"key":"10.1016\/j.micinf.2022.105081_bib12","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.micinf.2022.105081_bib13","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/infdis\/jiaa646","article-title":"Complement activation in the disease course of coronavirus disease 2019 and its effects on clinical outcomes","volume":"223","author":"de Nooijer","year":"2021","journal-title":"J\u00a0Infect Dis"},{"key":"10.1016\/j.micinf.2022.105081_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2020.107070","article-title":"Decreased complement C3 levels are associated with poor prognosis in patients with COVID-19: a retrospective cohort study","volume":"89","author":"Fang","year":"2020","journal-title":"Int Immunopharm"},{"key":"10.1016\/j.micinf.2022.105081_bib15","doi-asserted-by":"crossref","first-page":"25018","DOI":"10.1073\/pnas.2010540117","article-title":"Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients","volume":"117","author":"Holter","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.micinf.2022.105081_bib16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41577-020-0320-7","article-title":"Complement as a target in COVID-19?","volume":"20","author":"Risitano","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.micinf.2022.105081_bib17","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S2213-2600(21)00099-0","article-title":"Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"9","author":"Lescure","year":"2021","journal-title":"Lancet Respir Med"},{"key":"10.1016\/j.micinf.2022.105081_bib18","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1002\/jmv.25801","article-title":"Tocilizumab treatment in COVID-19: a single center experience","volume":"92","author":"Luo","year":"2020","journal-title":"J\u00a0Med Virol"},{"key":"10.1016\/j.micinf.2022.105081_bib19","doi-asserted-by":"crossref","DOI":"10.12659\/AJCR.927418","article-title":"Mild clinical course of COVID-19 in 3 patients receiving therapeutic monoclonal antibodies targeting C5 complement for hematologic disorders","volume":"21","author":"Araten","year":"2020","journal-title":"Am J Case Rep"},{"key":"10.1016\/j.micinf.2022.105081_bib20","first-page":"1373","article-title":"Eculizumab treatment for renal failure in a pediatric patient with COVID-19","volume":"33","author":"Mahajan","year":"2020","journal-title":"J\u00a0Nephrol"},{"key":"10.1016\/j.micinf.2022.105081_bib21","article-title":"Complement C3 vs C5 inhibition in severe COVID-19: early clinical findings reveal differential biological efficacy","volume":"220","author":"Mastellos","year":"2020","journal-title":"Clinical immunology (Orlando, Fla"},{"key":"10.1016\/j.micinf.2022.105081_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.imbio.2020.152001","article-title":"Endothelial injury and thrombotic microangiopathy in COVID-19: treatment with the lectin-pathway inhibitor narsoplimab","volume":"225","author":"Rambaldi","year":"2020","journal-title":"Immunobiology"},{"key":"10.1016\/j.micinf.2022.105081_bib23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0231892","article-title":"Inhibition of complement pathway activation with pozelimab, a fully human antibody to complement component C5","volume":"15","author":"Latuszek","year":"2020","journal-title":"PLoS One"},{"key":"10.1016\/j.micinf.2022.105081_bib24","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.4049\/jimmunol.1601121","article-title":"Interaction between multimeric von Willebrand factor and complement: a fresh look to the pathophysiology of microvascular thrombosis","volume":"199","author":"Bettoni","year":"2017","journal-title":"J\u00a0Immunol"},{"key":"10.1016\/j.micinf.2022.105081_bib25","doi-asserted-by":"crossref","first-page":"e380","DOI":"10.1093\/cid\/ciac153","article-title":"Efficacy and safety of sarilumab in hospitalized patients with COVID-19: a randomized clinical trial","volume":"75","author":"Sivapalasingam","year":"2022","journal-title":"Clin Infect Dis"},{"key":"10.1016\/j.micinf.2022.105081_bib26","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41586-020-2600-6","article-title":"Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis","volume":"588","author":"Carvelli","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.micinf.2022.105081_bib27","unstructured":"Centers for Disease Control and Prevention. Hospitalization and death by race\/ethnicity. https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/covid-data\/investigations-discovery\/hospitalization-death-by-race-ethnicity.html. (Accessed August 16, 2022)."},{"key":"10.1016\/j.micinf.2022.105081_bib28","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1086\/429631","article-title":"Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection","volume":"191","author":"Ip","year":"2005","journal-title":"J\u00a0Infect Dis"},{"key":"10.1016\/j.micinf.2022.105081_bib29","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.jaci.2021.11.004","article-title":"Severe COVID-19 is associated with hyperactivation of the alternative complement pathway","volume":"149","author":"Boussier","year":"2022","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"10.1016\/j.micinf.2022.105081_bib30","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1080\/21505594.2020.1816076","article-title":"Exploration of turn-positive RT-PCR results and factors related to treatment outcome in COVID-19: a retrospective cohort study","volume":"11","author":"Xiao","year":"2020","journal-title":"Virulence"},{"key":"10.1016\/j.micinf.2022.105081_bib31","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s40249-020-00723-1","article-title":"Abnormal immunity of non-survivors with COVID-19: predictors for mortality","volume":"9","author":"Zhao","year":"2020","journal-title":"Infect Dis Poverty"},{"key":"10.1016\/j.micinf.2022.105081_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.696085","article-title":"Serum complement C3 and C4 and COVID-19 severity and mortality: a systematic review and meta-analysis with meta-regression","volume":"12","author":"Zinellu","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.micinf.2022.105081_bib33","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1002\/eji.202048959","article-title":"Complement cascade in severe forms of COVID-19: recent advances in therapy","volume":"51","author":"Chouaki Benmansour","year":"2021","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.micinf.2022.105081_bib34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13613-020-00798-x","article-title":"Elevated plasma IL-6 and CRP levels are associated with adverse clinical outcomes and death in critically ill SARS-CoV-2 patients: inflammatory response of SARS-CoV-2 patients","volume":"11","author":"Lavillegrand","year":"2021","journal-title":"Ann Intensive Care"},{"key":"10.1016\/j.micinf.2022.105081_bib35","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/infdis\/jiab445","article-title":"Baseline severe acute respiratory syndrome viral load is associated with coronavirus disease 2019 severity and clinical outcomes: post hoc analyses of a phase 2\/3 trial","volume":"224","author":"Boyapati","year":"2021","journal-title":"J\u00a0Infect Dis"},{"key":"10.1016\/j.micinf.2022.105081_bib36","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/eji.1830190605","article-title":"Interleukin 6 stimulates synthesis of complement proteins factor B and C3 in human skin fibroblasts","volume":"19","author":"Katz","year":"1989","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.micinf.2022.105081_bib37","article-title":"Outcomes and biomarker analyses among patients with COVID-19 treated with interleukin 6 (IL-6) receptor antagonist sarilumab at a single institution in Italy","volume":"8","author":"Montesarchio","year":"2020","journal-title":"J\u00a0Immunotherapy Cancer"}],"container-title":["Microbes and Infection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1286457922001514?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1286457922001514?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T14:41:08Z","timestamp":1761144068000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1286457922001514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["S1286457922001514"],"URL":"https:\/\/doi.org\/10.1016\/j.micinf.2022.105081","relation":{},"ISSN":["1286-4579"],"issn-type":[{"value":"1286-4579","type":"print"}],"subject":[],"published":{"date-parts":[[2023,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Association of complement pathways with COVID-19 severity and outcomes","name":"articletitle","label":"Article Title"},{"value":"Microbes and Infection","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.micinf.2022.105081","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Masson SAS on behalf of Institut Pasteur.","name":"copyright","label":"Copyright"}],"article-number":"105081"}}