000			05285nam a22006617a 4500
008			240723s20242024 xxu||||| |||| 00| 0 eng d
022			_a2379-3708
024			_a178460 [pii]
040			_aOvid MEDLINE(R)
099			_a38483534
245			_aOutpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.
251			_aJci Insight. 9(8), 2024 Mar 14.
252			_aJCI insight. 9(8), 2024 Mar 14.
253			_aJCI insight
260			_c2024
260			_p2024 Mar 14
260			_fFY2024
265			_sepublish
265			_tMEDLINE
520			_aBACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS SARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.
546			_aEnglish
650			_a*Antibodies, Viral
650			_a*COVID-19
650			_a*COVID-19 Serotherapy
650			_a*Hospitalization
650			_a*Immunization, Passive
650			_a*SARS-CoV-2
650			_aAdult
650			_aAged
650			_aAntibodies, Neutralizing/bl [Blood]
650			_aAntibodies, Neutralizing/im [Immunology]
650			_aAntibodies, Viral/bl [Blood]
650			_aAntibodies, Viral/im [Immunology]
650			_aBlood Donors/sn [Statistics & Numerical Data]
650			_aCOVID-19/im [Immunology]
650			_aCOVID-19/th [Therapy]
650			_aDouble-Blind Method
650			_aFemale
650			_aHospitalization/sn [Statistics & Numerical Data]
650			_aHumans
650			_aImmunization, Passive/mt [Methods]
650			_aImmunoglobulin G/bl [Blood]
650			_aImmunoglobulin G/im [Immunology]
650			_aMale
650			_aMiddle Aged
650			_aOutpatients
650			_aSARS-CoV-2/im [Immunology]
650			_zAutomated
651			_aWashington Cancer Institute
657			_aJournal Article
657			_aRandomized Controlled Trial
657			_aResearch Support, N.I.H., Extramural
657			_aResearch Support, Non-U.S. Gov't
700			_aShenoy, Aarthi _bWCI
790			_aPark HS, Yin A, Barranta C, Lee JS, Caputo CA, Sachithanandham J, Li M, Yoon S, Sitaras I, Jedlicka A, Eby Y, Ram M, Fernandez RE, Baker OR, Shenoy AG, Mosnaim GS, Fukuta Y, Patel B, Heath SL, Levine AC, Meisenberg BR, Spivak ES, Anjan S, Huaman MA, Blair JE, Currier JS, Paxton JH, Gerber JM, Petrini JR, Broderick PB, Rausch W, Cordisco ME, Hammel J, Greenblatt B, Cluzet VC, Cruser D, Oei K, Abinante M, Hammitt LL, Sutcliffe CG, Forthal DN, Zand MS, Cachay ER, Raval JS, Kassaye SG, Marshall CE, Yarava A, Lane K, McBee NA, Gawad AL, Karlen N, Singh A, Ford DE, Jabs DA, Appel LJ, Shade DM, Lau B, Ehrhardt S, Baksh SN, Shapiro JR, Ou J, Na YB, Knoll MD, Ornelas-Gatdula E, Arroyo-Curras N, Gniadek TJ, Caturegli P, Wu J, Ndahiro N, Betenbaugh MJ, Ziman A, Hanley DF, Casadevall A, Shoham S, Bloch EM, Gebo KA, Tobian AA, Laeyendecker O, Pekosz A, Klein SL, Sullivan DJ
856			_uhttps://dx.doi.org/10.1172/jci.insight.178460 _zhttps://dx.doi.org/10.1172/jci.insight.178460
942			_cART _dArticle
999			_c14293 _d14293