The Antibody Response to SARS-CoV-2 Infection

Linda Hueston; Jen Kok; Ayla Guibone; Damien McDonald; George Hone; James Goodwin; Ian Carter; Kerri Basile; Indy Sandaradura; Susan Maddocks; Vitali Sintchenko; Nicole Gilroy; Sharon Chen; Dominic E Dwyer; Matthew V N O'Sullivan

doi:10.1093/ofid/ofaa387

The Antibody Response to SARS-CoV-2 Infection

Open Forum Infect Dis. 2020 Aug 27;7(9):ofaa387. doi: 10.1093/ofid/ofaa387. eCollection 2020 Sep.

Authors

Linda Hueston¹, Jen Kok¹, Ayla Guibone¹, Damien McDonald¹, George Hone¹, James Goodwin¹, Ian Carter¹, Kerri Basile¹, Indy Sandaradura^{1

2

3}, Susan Maddocks^{1

2}, Vitali Sintchenko^{1

3}, Nicole Gilroy², Sharon Chen^{1

3}, Dominic E Dwyer^{1

3}, Matthew V N O'Sullivan^{1

2

3}

Affiliations

¹ New South Wales Health Pathology, Institute of Clinical Pathology and Medical Research, Westmead, Australia.
² Department of Infectious Diseases, Westmead Hospital, Westmead, Australia.
³ Sydney Medical School, The University of Sydney, Sydney, Australia.

Abstract

Background: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of coronavirus disease 2019 (COVID-19) in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity.

Methods: A SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was developed and prospectively evaluated by comparison to the reference standard of NAT on respiratory tract samples from individuals with suspected COVID-19. Neutralizing antibody responses were measured in a subset of samples using a standard microneutralization assay.

Results: A total of 2753 individuals were eligible for the study (126 NAT-positive; prevalence, 4.6%). The median "window period" from illness onset to appearance of antibodies (range) was 10.2 (5.8-14.4) days. The sensitivity and specificity of either SARS-CoV-2 IgG, IgA, or IgM when collected ≥14 days after symptom onset were 91.3% (95% CI, 84.9%-95.6%) and 98.9% (95% CI, 98.4%-99.3%), respectively. The negative predictive value was 99.6% (95% CI, 99.3%-99.8%). The positive predictive value of detecting any antibody class was 79.9% (95% CI, 73.3%-85.1%); this increased to 96.8% (95% CI, 90.7%-99.0%) for the combination of IgG and IgA.

Conclusions: Measurement of SARS-CoV-2-specific antibody by IFA is an accurate method to diagnose COVID-19. Serological testing should be incorporated into diagnostic algorithms for SARS-CoV-2 infection to identify additional cases where NAT was not performed and resolve cases where false-negative and false-positive NATs are suspected. The majority of individuals develop robust antibody responses following infection, but the duration of these responses and implications for immunity remain to be established.

Keywords: COVID-19; SARS-CoV-2; antibody; diagnosis; serology.