Comparison of Antibody Class-Specific SARS-CoV-2 Serologies for the Diagnosis of Acute COVID-19

• Authors: Hans Verkerke, Emory University; Michael Horwath, Emory University; Bejan Saeedi, Emory University; Darra Boyer, Emory University; Jerry W. Allen, Emory University; Joshua Owens, Emory University; Connie Arthur, Emory University; Hirotomo Nakahara, Emory University; Jennifer Rha, Emory University; Kashyap Patel, Emory University; Shang-Chuen Wu, Emory University; Anu Paul, Emory University; Nini Yasin, Emory University; Jianmei Wang, Emory University; Sooncheon Shin, Emory University; DeAndre Brown, Emory University; Katherine Normile, Emory University; Lisa Cole, Emory University; Mark Meyers, Emory University; Heather Lin, Emory University; Emily Woods, Emory University; Jennifer Isaac, Emory University; Kari Broder, Emory University; Jenna Wade, Emory University; Robert C. Kauffman, Emory University; Ravi Patel, Emory University; Cassandra Josephson, Emory University; Stacian Reynolds, Emory University; Melanie Sherman, Emory University; Jens Wrammert, Emory University; David Alter, Emory University; Jeannette Guarner, Emory University; John Roback, Emory University; Andrew Neish, Emory University; Sean Stowell, Emory University
• Journal Title: JOURNAL OF CLINICAL MICROBIOLOGY
• Volume: Volume 59, Number 4
• Publisher: American Society for Microbiology | 2021-04-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/JCM.02026-20
• Subjects: Biology, Virology; Health Sciences, Immunology
• Keywords: antibodies; COVID-19; SARS-CoV-2; serology; spike; immunodiagnostics

Abstract

Accurate diagnosis of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical for appropriate management of patients with this disease. We examined the possible complementary role of laboratory-developed class-specific clinical serology in assessing SARS-CoV-2 infection in hospitalized patients. Serological tests for immunoglobulin G (IgG), IgA, and IgM antibodies against the receptor binding domain (RBD) of SARS-CoV-2 were evaluated using samples from real-time reverse transcription-quantitative PCR (qRT-PCR)-confirmed inpatient coronavirus disease 2019 (COVID-19) cases. We analyzed the influence of timing and clinical severity on the diagnostic value of class-specific COVID-19 serology testing. Cross-sectional analysis revealed higher sensitivity and specificity at lower optical density cutoffs for IgA in hospitalized patients than for IgG and IgM serology (IgG area under the curve [AUC] of 0.91 [95% confidence interval {CI}, 0.89 to 0.93] versus IgA AUC of 0.97 [95% CI, 0.96 to 0.98] versus IgM AUC of 0.95 [95% CI, 0.92 to 0.97]). The enhanced performance of IgA serology was apparent in the first 2 weeks after symptom onset and the first week after PCR testing. In patients requiring intubation, all three tests exhibit enhanced sensitivity. Among PCR-negative patients under investigation for SARS-CoV-2 infection, 2 out of 61 showed clear evidence of seroconversion IgG, IgA, and IgM. Suspected false-positive results in the latter population were most frequently observed in IgG and IgM serology tests. Our findings suggest the potential utility of IgA serology in the acute setting and explore the benefits and limitations of class-specific serology as a complementary diagnostic tool to PCR for COVID-19 in the acute setting.