Oral Presentation Lorne Infection and Immunity 2021

Serological testing for acute viral infections usually relies on detection of pathogen-specific IgM, but IgM typically has significant levels of cross-reactivity that hamper its utility, especially for infections such as SARS-CoV-2 (COVID-19) in low-prevalence settings. Indeed the proliferation of commercial ELISA and point of care (POC) tests for SARS-CoV-2 resulted in many inaccurate reports of incidence and prevalence, and IgM has not proven useful during the pandemic. We have developed a novel method for detection of the dimeric form of IgA (dIgA) using a chimera of rabbit- and human polymeric Ig receptor, termed CSC (chimeric secretory component), which binds only dIgA and not IgM. We have previously shown that dIgA is an acute phase biomarker in hepatitis A, hepatitis C and hepatitis E (Mohd-Hanafiah et al, 2018) and HIV (Seaton et al, 2017). UsingSARS-CoV-2 RBD antigen and recombinant CSC for capture (lateral flow POC) or detection (ELISA) of dIgA, we demonstrate that RBD-specific dIgA detects early seroconversion, reaching 100% sensitivity by 11 days after symptom onset. Importantly, the dIgA response was transient, declining rapidly after around 35-40 days after symptom onset and becoming negative on average around 80 days after symptom onset. Specificity of the dIgA tests appears to be very high, with no cross-reactivity observed in a limited number of acute seasonal coronavirus infected patients, and we will soon be testing a large panel of pre-COVID plasma samples. The SARS-CoV-2 dIgA assays should prove useful as an adjunct to detection of RNA/antigen in diagnosis, screening, and contact tracing, and for estimating the incidence of infection in serological surveys. In particular, the lateral flow POC dIgA tests will allow community-based testing and screening that will be important in responding to future waves of COVID-19, and we are pursuing commercial development of the tests.