@article{1bf54f66d78444f8bef7448dbda2d2c5,
title = "Outcomes of Convalescent Plasma with Defined High versus Lower Neutralizing Antibody Titers against SARS-CoV-2 among Hospitalized Patients: CoronaVirus Inactivating Plasma (CoVIP) Study",
abstract = "COVID-19 convalescent plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAbs) between different CCP donors. We conducted this study to evaluate the effectiveness and safety of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive by a SARS-CoV-2 nucleic acid amplification test and with symptoms for <10 days were eligible. Participants received either CCP with nAb titers of >1:640 (high-titer group) or ≥1:160 to 1:640 (standard-titer group) in addition to standard of care treatments. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes. Adverse events were contrasted by CCP titer. Between 28 August and 4 December 2020, 316 participants were screened, and 55 received CCP, with 14 and 41 receiving high- versus standard-titer CCP, respectively. Time to hospital discharge was shorter among participants receiving high- versus standard-titer CCP, accounting for death as a competing event (hazard ratio, 1.94; 95% confidence interval [CI], 1.05 to 3.58; Gray{\textquoteright}s P = 0.02). Severe adverse events (SAEs) (≥grade 3) occurred in 4 (29%) and 23 (56%) of participants receiving the high versus standard titer, respectively, by day 28 (risk ratio, 0.51; 95% CI, 0.21 to 1.22; Fisher{\textquoteright}s P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507).",
keywords = "antibodies, antibodies, convalescent plasma, coronavirus, immunology, immunology, neutralizing antibodies, SARS-CoV-2",
author = "Bartelt, {Luther A.} and Markmann, {Alena J.} and Bridget Nelson and Jessica Keys and Heather Root and Henderson, {Heather I.} and Joann Kuruc and Caroline Baker and Bhowmik, {D. Ryan} and Hou, {Yixuan J.} and Lakshmanane Premkumar and Caleb Cornaby and Schmitz, {John L.} and Susan Weiss and Yara Park and Ralph Baric and {de Silva}, {Aravinda M.} and Anne Lachiewicz and Sonia Napravnik and {van Duin}, David and Margolis, {David M.}",
note = "Funding Information: We thank all of our UNC CP donors, the staff at the UNC Blood Donation Center, including Hannah Thaxton and Taylor A. Whitaker, and the many volunteers who contributed to this work. This clinical study was supported by the UNC Health Foundation and the North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill with funding from the North Carolina Coronavirus Relief Fund established and appropriated by the North Carolina General Assembly. The NIH SeroNet Serocenter of Excellence Award (U54 CA260543) supported generation of laboratory data and the following investigators: A.J.M., L.P., S.N., S.W., D.M.M., A.M.d.S., R.B., and L.A.B. A.J.M. was previously funded by an NIH NIAID T32 AI007151. S.N. is also funded by the following NIH grants: UNC Center for AIDS Research P30 AI50410 and NA-ACCORD COVID-19 Supplement U01 AI069918. D.R.M. is funded by NIH F32 AI152296 and a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award and was previously funded by NIH NIAID T32 AI007151. H.I.H. is funded by NIH NIAID T32 AI007001. The laboratory assays for neutralizing antibody titers and SARS-CoV-2 specific antibody-binding assays were partially supported by The NIH NCI/NIAID SeroNet Serocenter of Excellence Award U54 CA260543. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. L.A.B. and D.M.M. conceptualized the study and the protocol with input from A.J.M., H.R., S.W., Y.P., R.B., A.M.d.S., A.L., S.N., and D.v.D. L.A.B., J.K., and D.M.M. wrote the study protocol and acquired the IND. L.A.B. and D.M.M. were overall program co-primary investigators. L.A.B. was the clinical primary investigator, and H.R., A.L., D.M.M., and D.v.D. were clinical coinvestigators J.K. was project administrator. J.K., C.B., and S.N. conceptualized the randomization scheme and oversaw randomization coding. S.W., Y.P. J.K., H.I.H., L.A.B., and D.M.M. acquired funding, analyzed data, and wrote the original draft. A.J.M., R.B., Y.J.H., L.P., C.C., J.L.S., R.B., and A.M.d.S. conceptualized the laboratory antibody assay methodology, and L.A.B., A.J.M., B.N., and R.B. analyzed the laboratory data. C.B., J.K., and B.N. curated data. S.N. validated data. L.A.B., B.N., J.K., H.I.H., and S.N. performed final analysis. B.N. made preliminary figures and tables with input from J.K. and L.A.B., and final tables and figures were made by S.N. L.A.B. wrote the original draft with input from A.J.M., S.N., D.v.D., and D.M.M. All authors reviewed and edited the final manuscript. D.M.M. and L.A.B. acquired funding. D.M.M. has provided consultancy to Merck outside this work, and owns common stock in Gilead Sciences. All other authors declare no conflict of interest. Funding Information: This clinical study was supported by the UNC Health Foundation and the North Carolina Policy Collaboratory at the University of North Carolina at Chapel Hill with funding from the North Carolina Coronavirus Relief Fund established and appropriated by the North Carolina General Assembly. The NIH SeroNet Serocenter of Excellence Award (U54 CA260543) supported generation of laboratory data and the following investigators: A.J.M., L.P., S.N., S.W., D.M.M., A.M.d.S., R.B., and L.A.B. A.J.M. was previously funded by an NIH NIAID T32 AI007151. S.N. is also funded by the following NIH grants: UNC Center for AIDS Research P30 AI50410 and NA-ACCORD COVID-19 Supplement U01 AI069918. D.R.M. is funded by NIH F32 AI152296 and a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award and was previously funded by NIH NIAID T32 AI007151. H.I.H. is funded by NIH NIAID T32 AI007001. The laboratory assays for neutralizing antibody titers and SARS-CoV-2 specific antibody-binding assays were partially supported by The NIH NCI/NIAID SeroNet Serocenter of Excellence Award U54 CA260543. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Publisher Copyright: {\textcopyright} 2022 Bartelt et al.",
year = "2022",
month = sep,
doi = "10.1128/mbio.01751-22",
language = "English (US)",
volume = "13",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "5",
}