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Author Notes:

Address correspondence to Andrew Neish, aneish@emory.edu, or Sean R. Stowell, srstowell@bwh.harvard.edu

Hans Verkerke and Michael Horwath contributed equally to this work. Author order was determined in order of increasing seniority.

We acknowledge with gratitude the patients who participated in our study. We also acknowledge the tireless efforts of medical technicians and clinical laboratory directors at Emory Hospital Midtown and Emory University Hospital, without whom these studies and the response to the pandemic in general would not be possible. This work would not have been possible without resources provided by the CDC for the development and implementation of this assay.



  • antibodies
  • COVID-19
  • SARS-CoV-2
  • serology
  • spike
  • immunodiagnostics

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

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Journal Title:



Volume 59, Number 4


Type of Work:

Article | Final Publisher PDF


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.

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© 2021 American Society for Microbiology.

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