TY - JOUR
T1 - Convalescent plasma anti–SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization
AU - Salazar, Eric
AU - Kuchipudi, Suresh V.
AU - Christensen, Paul A.
AU - Eagar, Todd
AU - Yi, Xin
AU - Zhao, Picheng
AU - Jin, Zhicheng
AU - Long, S. Wesley
AU - Olsen, Randall J.
AU - Chen, Jian
AU - Castillo, Brian
AU - Leveque, Christopher
AU - Towers, Dalton
AU - Lavinder, Jason
AU - Gollihar, Jimmy
AU - Cardona, Jose
AU - Ippolito, Gregory
AU - Nissly, Ruth
AU - Bird, Ian
AU - Greenawalt, Denver
AU - Rossi, Randall M.
AU - Gontu, Abhinay
AU - Srinivasan, Sreenidhi
AU - Poojary, Indira
AU - Cattadori, Isabella M.
AU - Hudson, Peter J.
AU - Josleyn, Nicole M.
AU - Prugar, Laura
AU - Huie, Kathleen
AU - Herbert, Andrew
AU - Bernard, David W.
AU - Dye, John M.
AU - Kapur, Vivek
AU - Musser, James M.
N1 - Funding Information:
We are deeply indebted to all of our volunteer plasma donors for their time, their gift, and their solidarity. We thank Katharine G. Dlouhy, Curt Hampton, and their team of coordinators and recruiters for outstanding efforts; Monisha Dey, Cheryl Chavez-East, John Rogers, Ahmed Shehabeldin, David Joseph, Guy Williams, Karen Thomas, and Curt Hampton, who were instrumental in efficiently managing the donor center; Jessica Thomas and Zejuan Li, Erika Walker, the very talented and dedicated molecular technologists, and the many labor pool volunteers in the Molecular Diagnostics Laboratory for their dedication to patient care; the many donor center and blood bank phlebotomists and technologists for their dedication to donor and blood safety; Sasha Pejerrey, Adrienne Winston, and Heather McConnell for editorial assistance; Brandi Robinson, Harrold Cano, and Cory Romero for technical assistance; Claude Moussa, Heather Patton, and the many members of the laboratory information technology team for rapidly implementing the necessary electronic workflows; Pamela McShane, Dilzi Mody, and the many members of the bioreposi-tory team for their meticulous management of patient samples; and Christina Talley, Susan Miller and Mary Clancy for consistent, thorough, and outstanding advice. We express our gratitude to Manuel Hinojosa and Mark Vassallo for their extensive efforts to rapidly procure resources and Roberta Schwartz for her efforts in implementing screening of asymptomatic individuals. We are indebted to Marc Boom and Dirk Sostman for their support and to many Houston citizens and businesses for their tremendous philanthropic support of this ongoing project, including, but not limited to, anonymous, Ann and John Bookout III, Carolyn and John Bookout, Ting Tsung and Wei Fong Chao Foundation, Ann and Leslie Doggett, Freeport LNG, the Hearst Foundations, Jer-old B. Katz Foundation, C. James and Carole Walter Looke, Diane and David Modesett, the Sherman Foundation, Paula and Joseph C. “Rusty” Walter III, and Aramco Americas. Jason S. McLellan (University of Texas at Austin) provided the monoclonal antibody CR3022 and the S protein expression vectors, and we thank the members of the Center for Systems and Synthetic Biology at the University of Texas at Austin for technical assistance. We thank Terumo BCT for continuously and rapidly supplying blood collection devices and supplies and Victoria Cavener, Meera Suren-dran Nair, and Team COVID-19 serology at Penn State for their timely and technical assistance and logistical support. We thank Nancy Jenkins and Neal Copeland for critical reading of the manuscript. This study was supported by the Fondren Foundation and Houston Methodist Hospital and Research Institute (to JMM). This research has been funded in whole or part with federal funds under a contract from the National Institute of Allergy and Infectious Diseases, NIH contract 75N93019C00050 (to JL and GI). A portion of this work was funded through Cooperative Agreement W911NF-12-1-0390 by the Army Research Office (to JG). We acknowledge seed funding from the Huck Institutes of the Life Sciences for the studies at Penn State (to SVK), together with the Huck Distinguished Chair in Global Health award (to VK). Funding was also provided through the CARES Act, with programmatic oversight from the Military Infectious Diseases Research Program (to JMD). Opinions, discussions, conclusions, interpretations, and recommendations are those of the authors and are not necessarily endorsed by the US Army. The mention of trade names or commercial products does not constitute endorsement or recommendation for use by the Department of the Army or the Department of Defense. The graphical abstract was created using BioRender.
Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), anti–receptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was ≥80% when anti-RBD or anti-ECD titers were ≥1:1350. Of all donors, 37% lacked VN titers of ≥160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of ≥1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of ≥1:160, and all of them had anti-RBD titers of ≥1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of ≥1:1350 may provide critical information about protection against COVID-19 disease.
AB - The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), anti–receptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was ≥80% when anti-RBD or anti-ECD titers were ≥1:1350. Of all donors, 37% lacked VN titers of ≥160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of ≥1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of ≥1:160, and all of them had anti-RBD titers of ≥1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of ≥1:1350 may provide critical information about protection against COVID-19 disease.
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U2 - 10.1172/JCI141206
DO - 10.1172/JCI141206
M3 - Article
C2 - 32910806
AN - SCOPUS:85091734248
VL - 130
SP - 6728
EP - 6738
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 12
ER -