The Antibody Response to SARS-CoV-2 Infection

Abstract

Testing for SARS-CoV-2-specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of COVID-19 in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity. A SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for IgG, IgA and 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. 2753 individuals were eligible for the study (126 NAT positive, prevalence 4·6%). The median ‘window period’ from illness onset to appearance of antibody was 10·2 days (range 5·8 – 14·4). The sensitivity and specificity of either SARS-CoV-2 IgG, IgA or IgM when collected 14 days or more after symptom onset was 91·3% (95% CI 84·9-95·6) and 98·9% (98·4-99·3), respectively. The negative predictive value was 99·6% (99·3-99·8). The positive predictive value of detecting any antibody class was 79·9% (73·3-85·1); this increased to 96·8% (90·7-99·0) for the combination of IgG and IgA. 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.