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

The Antibody Response to SARS-CoV-2 Infection

Linda Hueston  1 , Jen Kok  1 , Ayla Guibone  1 , Damien McDonald  1 , George Hone  1 , James Goodwin  1 , Ian Carter  1 , Kerri Basile  1 , Indy Sandaradura  1   2   3 , Susan Maddocks  1   2 , Vitali Sintchenko  1   3 , Nicole Gilroy  2 , Sharon Chen  1   3 , Dominic E Dwyer  1   3 , Matthew V N O'Sullivan  1   2   3
Affiliations

The Antibody Response to SARS-CoV-2 Infection

Linda Hueston et al. Open Forum Infect Dis. .

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.

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Figures

Figure 1.
Figure 1.
Positive immunofluorescent antibody test showing apple-green cytoplasmic fluorescence (1600× magnification).
Figure 2.
Figure 2.
Study flow diagram. Abbreviations: IFA, immunofluorescent antibody; NAT, nucleic acid testing.
Figure 3.
Figure 3.
Boxplots of severe acute respiratory syndrome coronavirus 2–specific antibody titers seen in true-positive and false-positive immunofluorescent antibody tests. Abbreviations: IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M.
Figure 4.
Figure 4.
Dynamics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response. A, Median antibody titers over time. B, Proportion of individuals with positive SARS-CoV-2-specific antibody results over time. Numbers below the axis indicate individuals tested at each time point. Abbreviations: IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M.
See this image and copyright information in PMC

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