Donor Anti-Spike Immunity is Related to Recipient Recovery and Can Predict the Efficacy of Convalescent Plasma Units
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Abstract
Background
The novel coronavirus, SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.31 million people within the last year and yet no cure exists. Whereas passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable option, selection of optimal units for therapy and lack of clear therapeutic benefit from transfusion remain as barriers to the use of CCP.
Study design and methods
To identify plasma that is expected to benefit recipients, we measured anti-SARS-CoV2 antibody levels using clinically available serological assays and correlated with the neutralizing activity of CCP from donors. Neutralizing titer of plasma samples was measured by assaying infectivity of SARS-CoV-2 spike protein pseudotyped retrovirus particles in the presence of dilutions of plasma samples. We also used this assay to identify evidence of passive transfusion of neutralizing activity in CCP recipients.
Results
Viral neutralization and anti-spike protein antibodies in 109 samples from 87 plasma donors were highly varied but modestly correlated with each other. Recipients who died of COVID-19 were found to have been transfused with units with lower anti-spike antibody levels and neutralizing activity. Passive transfer of neutralization activity was documented in 62% of antibody naive plasma recipients.
Conclusions
Since viral neutralization is the goal of CCP transfusion, our observations not only support the use of anti-spike SARS-CoV2 serology tests to identify beneficial CCP units, but also support the therapeutic value of convalescent plasma with high titers of anti-spike antibodies.
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SciScore for 10.1101/2021.02.25.21252463: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: CCP recipients and clinical parameters: This study was approved by the University of Wisconsin Institutional Review Board.
Consent: All cases met criteria for enrollment in the Mayo Clinic Expanded Access Protocol (IND # 20-003312, EAP) and gave written, informed consent for CCP transfusion and data collection.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Anti-SARS-CoV2 antibody/serology assays: Anti-SARS-CoV2 Spike antibodies (Ortho Diagnostics, Markham, Ontario): This assay is a qualitative, automated, … SciScore for 10.1101/2021.02.25.21252463: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: CCP recipients and clinical parameters: This study was approved by the University of Wisconsin Institutional Review Board.
Consent: All cases met criteria for enrollment in the Mayo Clinic Expanded Access Protocol (IND # 20-003312, EAP) and gave written, informed consent for CCP transfusion and data collection.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Anti-SARS-CoV2 antibody/serology assays: Anti-SARS-CoV2 Spike antibodies (Ortho Diagnostics, Markham, Ontario): This assay is a qualitative, automated, two stage immunometric assay to identify both anti-SARS-CoV2 Spike protein IgG and IgM. anti-SARS-CoV2 Spike protein IgGsuggested: NoneIgMsuggested: None2 nucleocapsid IgG assay (Abbott Laboratories, Chicago, IL): This is an automated, two-step immunoassay for the detection of IgG antibodies to SARS-CoV2 nucleocapsid proteins. SARS-CoV2 nucleocapsid proteins.suggested: NoneAlthough neither of these assays are used clinically as quantitative tests for the purposes of this study both the S/CO and the INDEX were considered to define the amount of anti-SARS-CoV2 antibodies in each sample. anti-SARS-CoV2suggested: NoneExperimental Models: Cell Lines Sentences Resources Cell lines: 293T cells were obtained from ATCC and maintained in DMEM with 10% FBS, 100 U/ml penicillin, 100 µg/ml streptomycin, 0.25 µg/ml amphotericin B, and 2mM L-glutamine ( 293Tsuggested: NoneThe virus stocks were titrated on 293T-ACE2 cells to determine an optimal volume of the virus to be used in neutralization assays. 293T-ACE2suggested: RRID:CVCL_YZ65)Software and Algorithms Sentences Resources 2 nucleocapsid IgG assay (Abbott Laboratories, Chicago, IL): This is an automated, two-step immunoassay for the detection of IgG antibodies to SARS-CoV2 nucleocapsid proteins. Abbott Laboratoriessuggested: NoneAll statistical analysis was done using the GraphPad Prism software (GraphPad Software, Inc La Jolla, CA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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