MSS06: EXPERIENCE OF A NOVEL BETACORONAVIRUS MULTIPLEX MICROSPHERE IMMUNOASSAY IN A DEPLOYED MILITARY FIELD HOSPITAL
Franklin A Valdera, MD1; Patrick McCarthy, MD1; Alexandra Adams, MD MPH1; Elizabeth Carpenter, MD1; Florian Krammer, PhD2; Eric Laing, PhD3; Christopher Broder, PhD3; Daniel Stadlbauer, PhD2; Timothy Burgess, MD4; Kevin Chung, MD5; Guy T Clifton, MD1; 1Department of Surgery, Brooke Army Medical Center; 2Department of Microbiology, Icahn School of Medicine at Mt. Sinai; 3Department of Microbiology and Immunology, Uniformed Services University of Health Sciences; 4Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences; 5Department of Medicine, Uniformed Services University of Health Science
Objectives: As SARS-CoV-2 persists, need for accurate and rapid diagnostic testing remains crucial. Enzyme-linked immunosorbent assay (ELISA) based testing remains the gold-standard for antibodies. Multiplexed microsphere immunoassays (MMIA) also detect and quantify antibody levels but offer an advantage of testing for multiple antigens simultaneously in small blood volumes. Novel strains of SARS-CoV-2 with altered spike proteins highlight the value of the ability to detect antibodies to multiple spike proteins while also testing for other infectious antigens in a single test. We sought to assess the diagnostic performance of the betacoronavirus MMIA, via specificity and sensitivity, when compared with the SARS-CoV-2 IgG antibody ELISA tests.
Methods: Conducted during deployment of personnel from the 9th and 531st Hospital Centers, and 44th Medical Brigade to Javits New York Medical Station (JMS). All active duty personnel assigned to JMS and patients admitted to JMS with PCR verified infection were invited to participate. Participants could receive two different SARS-CoV-2 ELISA tests: the SARS-CoV-2 antibody ELISA test developed by Amant et. al., and a novel betacoronavirus MMIA developed by Laing et. al. The former received FDA EUA at the time of the study and was considered the gold standard. MMIA utilizes magnetic microspheres labeled with viral spike proteins from SARS-CoV-2. After adding patient sera and allowing for binding, anti-human IgG antibodies labeled with a biotin conjugate are mixed, allowing for optically detectable signaling upon binding.
Results: Of 591 eligible soldiers deployed to JMS, 336 (56.8%) enrolled. Five soldiers had positive IgG ELISA titers detected at 1/80(n=3), 1/160(n=1), and 1/2880(n=1). Only the two soldiers with titers greater than 1/80 also had positive SARS-CoV-2 MMIA results, for both IgG. Additionally, 35/76 patients(46.1%), most with history of severe COVID-19, enrolled. All 35 were ELISA positive for SARS-CoV-2 IgG, with 33/35 having the highest quantifiable titer (1/2880) for this test and two with 1/960. All admitted patients were SARS-CoV-2 MMIA IgG-positive. For both groups of patients, MMIA had a sensitivity of 92.5% and specificity of 100% compared to ELISA for detecting SARS-CoV-2 IgG. MMIA demonstrated complete concordance with ELISA for all subjects (two soldiers and 35 patients) with serum IgG titers >1/80. Assay discordance was noted for the three soldiers whose serum IgG titers by ELISA were 1/80, the lowest reported positive dilution.
Conclusion: MMIA antibody testing performed well compared to ELISA testing for detecting SARS-CoV-2 IgG antibodies with complete concordance for IgG titers over 1/80.