TY - JOUR
T1 - A Hemagglutination-Based Semiquantitative Test for Point-of-Care Determination of SARS-CoV-2 Antibody Levels
AU - Kruse, Robert L.
AU - Huang, Yuting
AU - Lee, Alyssa
AU - Zhu, Xianming
AU - Shrestha, Ruchee
AU - Laeyendecker, Oliver
AU - Littlefield, Kirsten
AU - Pekosz, Andy
AU - Bloch, Evan M.
AU - Tobian, Aaron A.R.
AU - Wang, Zack Z.
N1 - Funding Information:
This work was funded by the Johns Hopkins Department of Pathology Fred and Janet Sanfilippo Research Award (R.L.K.), and partially supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease (grant R01DK106109 [Z.Z.W.]).
Funding Information:
We thank Peter Clausen and Kim Kristensen for production of EldonCards and executing pilot testing, and we thank Kasper Juul Hedegaard, Hans-Ole Hedegaard, and Michael L. Hansen of Eldon Biologicals for their advice and coordination during the project. We also thank Heather Smetana and Melissa Neally for providing reagents and technical advice. This work was funded by the Johns Hopkins Department of Pathology Fred and Janet Sanfilippo Research Award (R.L.K.), and partially supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease (grant R01DK106109 [Z.Z.W.]). R.L.K, Y.H., and Z.Z.W. are coinventors on a patent application related to the fusion protein detection agent for SARS-CoV-2. We recruited Eldon Biologicals for the collaboration, but the data and conclusions here are fully the authors’ and independent from Eldon Biologicals. Beyond testing cards, no formal sponsored research funding was received from Eldon Biologicals.
Publisher Copyright:
© 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/12
Y1 - 2021/12
N2 - Serologic point-of-care tests to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information. To address this, we developed a novel antibody test leveraging hemagglutination, employing a dry card format currently used for typing ABO blood groups. Two hundred COVID-19 patient and 200 control plasma samples were reconstituted with O-negative red blood cells (RBCs) to form whole blood and added to dried viral-antibody fusion protein, followed by a stirring step and a tilting step, 3-min incubation, and a second tilting step. The sensitivities of the hemagglutination test, Euroimmun IgG enzyme-linked immunosorbent assay (ELISA), and receptor binding domain (RBD)-based CoronaChek lateral flow assay were 87.0%, 86.5%, and 84.5%, respectively, using samples obtained from recovered COVID-19 individuals. Testing prepandemic samples, the hemagglutination test had a specificity of 95.5%, compared to 97.3% and 98.9% for the ELISA and CoronaChek, respectively. A distribution of agglutination strengths was observed in COVID-19 convalescent-phase plasma samples, with the highest agglutination score (4) exhibiting significantly higher neutralizing antibody titers than weak positives (2) (P, 0.0001). Strong agglutinations were observed within 1 min of testing, and this shorter assay time also increased specificity to 98.5%. In conclusion, we developed a novel rapid, point-of-care RBC agglutination test for the detection of SARS-CoV-2 antibodies that can yield semiquantitative information on neutralizing antibody titer in patients. The 5-min test may find use in determination of serostatus prior to vaccination, postvaccination surveillance, and travel screening.
AB - Serologic point-of-care tests to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information. To address this, we developed a novel antibody test leveraging hemagglutination, employing a dry card format currently used for typing ABO blood groups. Two hundred COVID-19 patient and 200 control plasma samples were reconstituted with O-negative red blood cells (RBCs) to form whole blood and added to dried viral-antibody fusion protein, followed by a stirring step and a tilting step, 3-min incubation, and a second tilting step. The sensitivities of the hemagglutination test, Euroimmun IgG enzyme-linked immunosorbent assay (ELISA), and receptor binding domain (RBD)-based CoronaChek lateral flow assay were 87.0%, 86.5%, and 84.5%, respectively, using samples obtained from recovered COVID-19 individuals. Testing prepandemic samples, the hemagglutination test had a specificity of 95.5%, compared to 97.3% and 98.9% for the ELISA and CoronaChek, respectively. A distribution of agglutination strengths was observed in COVID-19 convalescent-phase plasma samples, with the highest agglutination score (4) exhibiting significantly higher neutralizing antibody titers than weak positives (2) (P, 0.0001). Strong agglutinations were observed within 1 min of testing, and this shorter assay time also increased specificity to 98.5%. In conclusion, we developed a novel rapid, point-of-care RBC agglutination test for the detection of SARS-CoV-2 antibodies that can yield semiquantitative information on neutralizing antibody titer in patients. The 5-min test may find use in determination of serostatus prior to vaccination, postvaccination surveillance, and travel screening.
KW - SARS-CoV-2
KW - antibody
KW - hemagglutination
KW - point of care
KW - red blood cell
KW - serology
UR - http://www.scopus.com/inward/record.url?scp=85122047369&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122047369&partnerID=8YFLogxK
U2 - 10.1128/JCM.01186-21
DO - 10.1128/JCM.01186-21
M3 - Article
C2 - 34469185
AN - SCOPUS:85122047369
SN - 0095-1137
VL - 59
JO - Journal of Clinical Microbiology
JF - Journal of Clinical Microbiology
IS - 12
M1 - e01186-21
ER -