Gang Xu1, Anthony J Emanuel1, Satish Nadig2, Shikhar Mehrotra2, Brittany A Caddell1, Scott R Curry3, Frederick S Nolte1, Nikolina Babic1. 1. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston SC. 2. Department of Surgery, Microbiology and Immunology, Medical University of South Carolina, Charleston SC. 3. Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston SC.
Abstract
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing is an important tool in assessment of pandemic progress, contact tracing, and identification of recovered coronavirus disease 2019 (COVID-19) patients. We evaluated an orthogonal testing algorithm (OTA) to improve test specificity in these use cases. METHODS: A two-step OTA was applied where individuals who initially tested positive were tested with a second test. The first-line test, detecting IgG antibodies to the viral nucleocapsid protein was validated in 130 samples and the second-line test, detecting IgG antibodies to the viral spike protein in 148 samples. The OTA was evaluated in 4,333 clinical patient specimens. The seropositivity rates relative to the SARS-CoV-2 PCR positivity rates were evaluated from our entire patient population data (n = 5,102). RESULTS: The first-line test resulted in a clinical sensitivity of 96.4% (95% CI; 82.3% to 99.4%), and specificity of 99.0% (95% CI; 94.7% to 99.8%), whereas the second-line test had a sensitivity of 100% (95% CI; 87.7% to 100%) and specificity of 98.4% (95% CI; 94.2% to 99.5%). Using the OTA, 78/98 (80%) of initially positive SARS-CoV-2 IgG results were confirmed with a second-line test, while 11/42 (26%) of previously diagnosed COVID-19 patients had no detectable antibodies as long as 94 days post PCR diagnosis. CONCLUSION: Our results show that an OTA can be used to identify patients who require further follow-up due to potential SARS CoV-2 IgG false positive results. In addition, serological testing may not be sufficiently sensitive to reliably detect prior COVID-19 infection.
BACKGROUND:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing is an important tool in assessment of pandemic progress, contact tracing, and identification of recovered coronavirus disease 2019 (COVID-19) patients. We evaluated an orthogonal testing algorithm (OTA) to improve test specificity in these use cases. METHODS: A two-step OTA was applied where individuals who initially tested positive were tested with a second test. The first-line test, detecting IgG antibodies to the viral nucleocapsid protein was validated in 130 samples and the second-line test, detecting IgG antibodies to the viral spike protein in 148 samples. The OTA was evaluated in 4,333 clinical patient specimens. The seropositivity rates relative to the SARS-CoV-2 PCR positivity rates were evaluated from our entire patient population data (n = 5,102). RESULTS: The first-line test resulted in a clinical sensitivity of 96.4% (95% CI; 82.3% to 99.4%), and specificity of 99.0% (95% CI; 94.7% to 99.8%), whereas the second-line test had a sensitivity of 100% (95% CI; 87.7% to 100%) and specificity of 98.4% (95% CI; 94.2% to 99.5%). Using the OTA, 78/98 (80%) of initially positive SARS-CoV-2 IgG results were confirmed with a second-line test, while 11/42 (26%) of previously diagnosed COVID-19patients had no detectable antibodies as long as 94 days post PCR diagnosis. CONCLUSION: Our results show that an OTA can be used to identify patients who require further follow-up due to potential SARS CoV-2 IgG false positive results. In addition, serological testing may not be sufficiently sensitive to reliably detect prior COVID-19infection.
Authors: Fatima Amanat; Daniel Stadlbauer; Shirin Strohmeier; Thi H O Nguyen; Veronika Chromikova; Meagan McMahon; Kaijun Jiang; Guha Asthagiri Arunkumar; Denise Jurczyszak; Jose Polanco; Maria Bermudez-Gonzalez; Giulio Kleiner; Teresa Aydillo; Lisa Miorin; Daniel S Fierer; Luz Amarilis Lugo; Erna Milunka Kojic; Jonathan Stoever; Sean T H Liu; Charlotte Cunningham-Rundles; Philip L Felgner; Thomas Moran; Adolfo García-Sastre; Daniel Caplivski; Allen C Cheng; Katherine Kedzierska; Olli Vapalahti; Jussi M Hepojoki; Viviana Simon; Florian Krammer Journal: Nat Med Date: 2020-05-12 Impact factor: 53.440
Authors: Andrew Bryan; Gregory Pepper; Mark H Wener; Susan L Fink; Chihiro Morishima; Anu Chaudhary; Keith R Jerome; Patrick C Mathias; Alexander L Greninger Journal: J Clin Microbiol Date: 2020-07-23 Impact factor: 5.948
Authors: Emily Degli-Angeli; Joan Dragavon; Meei-Li Huang; Danijela Lucic; Gavin Cloherty; Keith R Jerome; Alexander L Greninger; Robert W Coombs Journal: J Clin Virol Date: 2020-05-28 Impact factor: 3.168
Authors: K L Chew; S S Tan; S Saw; A Pajarillaga; S Zaine; C Khoo; W Wang; P Tambyah; R Jureen; S K Sethi Journal: Clin Microbiol Infect Date: 2020-06-09 Impact factor: 8.067