Outcomes of Convalescent Plasma with Defined High versus Lower Neutralizing Antibody Titers against SARS-CoV-2 among Hospitalized Patients: CoronaVirus Inactivating Plasma (CoVIP) Study.

Autor: Bartelt LA; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Markmann AJ; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Nelson B; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Keys J; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Root H; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; The AIDS Center at Montefiore, Division of Infectious Diseases, Montefiore Medical Center, Bronx, New York, USA., Henderson HI; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Kuruc J; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; UNC HIV Cure Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Baker C; UNC HIV Cure Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Bhowmik DR; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Hou YJ; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA., Premkumar L; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Cornaby C; Department of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Schmitz JL; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; Department of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Weiss S; Department of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; Department of Pathology, Carolinas Pathology Group, Atrium Health Carolinas Medical Center, Charlotte, North Carolina, USA., Park Y; Department of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Baric R; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA., de Silva AM; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Lachiewicz A; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Napravnik S; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA., van Duin D; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA., Margolis DM; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.; UNC HIV Cure Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Jazyk: angličtina
Zdroj: MBio [mBio] 2022 Oct 26; Vol. 13 (5), pp. e0175122. Date of Electronic Publication: 2022 Sep 22.
DOI: 10.1128/mbio.01751-22
Abstrakt: 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'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's P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507). IMPORTANCE In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. Although limited by a small study size, these findings support further study of high-nAb-titer CCP defined as >1:640 in the treatment of COVID-19.
Databáze: MEDLINE
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