Sensitive detection of total anti-Spike antibodies and isotype switching in asymptomatic and symptomatic COVID-19 patients

Goh, Yun Shan; Chavatte, Jean-Marc; Jieling, Alicia Lim; Lee, Bernett; Hor, Pei Xiang; Amrun, Siti Naqiah; Yi-Pin Lee, Cheryl; Sin-Ling Chee, Rhonda; Wang, Bei; Lee, Chia Yin; Xian Ngoh, Eve Zhi; Wang, Cheng-I; Young, Barnaby Edward; Tambyah, Paul A.; Kalimuddin, Shirin; Pada, Surinder; Tan, Seow-Yen; Sun, Louisa Jin; I-Cheng Chen, Mark; Leo, Yee-Sin; Lye, David C.; Ng, Lisa F.P.; Pin Lin, Raymond Tzer; Renia, Laurent

Early detection of infections is crucial to limit the spread of coronavirus 2019 disease (COVID-19). Here, we develop a flow cytometry-based assay to detect SARS-CoV-2 Spike protein (S protein) antibodies in COVID-19 patients. The assay detects specific IgM, IgA and IgG in COVID-19 patients and also the acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response is significantly higher at a later stage of the infection. Furthermore, asymptomatic COVID-19 patients also develop specific IgM, IgA and IgG, with IgG1 as the most dominant subclass. Although the antibody levels are lower in asymptomatic infections, the assay is highly sensitive and detect 97% of asymptomatic infections. These findings demonstrate that the assay can be used for serological analysis of symptomatic infections, and also asymptomatic infections, which may, otherwise, go undetected.