{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T04:22:22Z","timestamp":1754108542537,"version":"3.41.2"},"reference-count":136,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The COVID\u201019 pandemic caused by the SARS\u2010CoV\u20102 virus was arguably one of the worst public health disasters of the last 100\u2009years. As many infectious disease experts were focused on influenza, MERS, ZIKA, or Ebola as potential pandemic\u2010causing agents, SARS\u2010CoV\u20102 appeared to come from nowhere and spread rapidly. As with any zoonotic agent, the initial pathogen was able to transmit to a new host (humans), but it was poorly adapted to the immune environment of the new host and resulted in a maladapted immune response. As the host\u2010pathogen interaction evolved, subsequent variants of SARS\u2010CoV\u20102 became less pathogenic and acquired immunity in the host provided protection, at least partial protection, to new variants. As the host\u2010pathogen interaction has changed since the beginning of the pandemic, it is possible the clinical results discussed here may not be applicable today as they were at the start of the pandemic. With this caveat in mind, we present an overview of the immune response of severe COVID\u201019 from a clinical research perspective and examine clinical trials utilizing immunomodulating agents to further elucidate the importance of hyperinflammation as a factor contributing to severe COVID\u201019 disease.<\/jats:p>","DOI":"10.1111\/imr.13422","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T11:48:48Z","timestamp":1731757728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lessons Learned From Clinical Trials of Immunotherapeutics for COVID\u201019"],"prefix":"10.1111","volume":"329","author":[{"given":"Inyeong","family":"Lee","sequence":"first","affiliation":[{"name":"R&amp;D Department QoolAbs  Carlsbad California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6586-004X","authenticated-orcid":false,"given":"Christopher R.","family":"Lupfer","sequence":"additional","affiliation":[{"name":"Department of Biology Brigham Young University\u2010Idaho  Rexburg Idaho USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,16]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"WHO \u201cWHO COVID\u201019 Dashboard \u201dhttps:\/\/data.who.int\/dashboards\/covid19."},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3345\/cep.2020.00493"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/W12061598"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2107"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)30211\u20107"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1585"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa272"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)30183\u20105"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.03.047"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010020\u20101051\u20109"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8111718"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010020\u201002646\u20109"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3COVA0820\u2010410RRR"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.681516"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abd1554"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.eabd6197"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2020.0994"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.138999"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007008"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/v16020201"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143648"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201034895\u20101"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0241097"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000753\u20107"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.610300"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102600\u20106"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010021\u201004735\u20101"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.671052"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2010540117\/\u2010\/DCSupplemental"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.7326\/L20\u20100227"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100040\u20101715835"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.631226"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03065-y"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc6027"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.001694"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201005186\u2010y"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(22)00002\u20109"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149575"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4585"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666\u20105247(23)00095\u20102"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.949413"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010020\u20100602\u20104"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.04.017"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010020\u20100901\u20109"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.664209"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14010029"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/9551163"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010023\u201004388\u20108"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab125"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201026888\u20103"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010022\u201001215\u20107"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010021\u201001281\u20101"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12010042"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2021.04.002"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155492"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010023\u201004516\u20104"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00006.2022"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(21)00237\u2010X"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2024.106217"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab732"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade8272"},{"issue":"2","key":"e_1_2_6_65_1","article-title":"Fostamatinib for the Treatment of Hospitalized Patients With COVID\u201019 Who Required Oxygen Supplementation: Results of a Phase 3 Trial","volume":"10","author":"Gotur D. B.","year":"2023","journal-title":"Open Forum Infectious Diseases"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2101643"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocpiqo.2021.03.007"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(22)00088\u20101"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000791\u20101"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102763"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010020\u201002960\u20100"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054\u2010020\u201003158\u20100"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.11043"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.29639"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2021.08.044"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa350"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1002.030482"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac523"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.05.020"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(21)00384\u20102"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107916"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.07.001"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(20)30566\u2010X"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2209760"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2021.06.002"},{"key":"e_1_2_6_86_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000513"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02566"},{"key":"e_1_2_6_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxad065"},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.23257"},{"key":"e_1_2_6_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2022.03.002"},{"key":"e_1_2_6_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011\u2010023\u201001718\u2010y"},{"key":"e_1_2_6_92_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010\u2010022\u201001904\u2010w"},{"key":"e_1_2_6_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201043644\u2010x"},{"key":"e_1_2_6_94_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2028836"},{"key":"e_1_2_6_95_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2028700"},{"key":"e_1_2_6_96_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010021\u201006507\u2010x"},{"key":"e_1_2_6_97_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2030340"},{"key":"e_1_2_6_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(21)00099\u20100"},{"key":"e_1_2_6_99_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac153"},{"key":"e_1_2_6_100_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2021.0111"},{"key":"e_1_2_6_101_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100433"},{"key":"e_1_2_6_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00676\u20100"},{"key":"e_1_2_6_103_1","unstructured":"WHO \u201cTherapeutics and COVID\u201019: Living Guideline \u201dhttps:\/\/app.magicapp.org\/#\/guideline\/nBkO1E."},{"key":"e_1_2_6_104_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005716"},{"key":"e_1_2_6_105_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000005683"},{"key":"e_1_2_6_106_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0261113"},{"key":"e_1_2_6_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100590"},{"key":"e_1_2_6_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2020.108598"},{"key":"e_1_2_6_109_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo2341"},{"key":"e_1_2_6_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100925"},{"key":"e_1_2_6_111_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102022\u2010326952"},{"key":"e_1_2_6_112_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14132716"},{"key":"e_1_2_6_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2020.105751"},{"key":"e_1_2_6_114_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab405"},{"key":"e_1_2_6_115_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13061760"},{"key":"e_1_2_6_116_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12030419"},{"key":"e_1_2_6_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104667"},{"key":"e_1_2_6_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000329\u2010x"},{"key":"e_1_2_6_119_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102554"},{"key":"e_1_2_6_120_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.16685"},{"key":"e_1_2_6_121_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab010"},{"key":"e_1_2_6_122_1","doi-asserted-by":"publisher","DOI":"10.2147\/OAEM.S405555"},{"key":"e_1_2_6_123_1","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2022.0025"},{"key":"e_1_2_6_124_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2020.198088"},{"key":"e_1_2_6_125_1","doi-asserted-by":"publisher","DOI":"10.31488\/ejrm.121"},{"key":"e_1_2_6_126_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010020\u20100372\u2010x"},{"key":"e_1_2_6_127_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2022.04.016"},{"key":"e_1_2_6_128_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100773"},{"key":"e_1_2_6_129_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2016638"},{"key":"e_1_2_6_130_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(21)00160\u20100"},{"key":"e_1_2_6_131_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)01744\u2010X"},{"key":"e_1_2_6_132_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021436"},{"key":"e_1_2_6_133_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.8516"},{"key":"e_1_2_6_134_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10081607"},{"key":"e_1_2_6_135_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049756\u20102"},{"key":"e_1_2_6_136_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac218"},{"key":"e_1_2_6_137_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S356547"}],"container-title":["Immunological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imr.13422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T13:03:08Z","timestamp":1739451788000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imr.13422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,16]]},"references-count":136,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/imr.13422"],"URL":"https:\/\/doi.org\/10.1111\/imr.13422","archive":["Portico"],"relation":{},"ISSN":["0105-2896","1600-065X"],"issn-type":[{"type":"print","value":"0105-2896"},{"type":"electronic","value":"1600-065X"}],"subject":[],"published":{"date-parts":[[2024,11,16]]},"assertion":[{"value":"2024-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13422"}}