Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera: A semi-quantitative, high throughput, microscopy-based assay expands existing approaches to measure SARS-CoV-2 specific antibody levels in human sera

Constantin Pape 1 2, Roman Remme 1, Adrian Wolny 1 2, Sylvia Olberg 3, Steffen Wolf 1, Lorenzo Cerrone 1, Mirko Cortese 4, Severina Klaus 5, Bojana Lucic 6, Stephanie Ullrich 3, Maria Anders-Össwein 3, Stefanie Wolf 3, Berati Cerikan 4, Christopher J Neufeldt 4, Markus Ganter 5, Paul Schnitzler 3, Uta Merle 7, Marina Lusic 6 8, Steeve Boulant 3 9, Megan Stanifer 4 9, Ralf Bartenschlager 4 8, Fred A Hamprecht 1, Anna Kreshuk 2, Christian Tischer 2, Hans-Georg Kräusslich 3 8, Barbara Müller 3, Vibor Laketa 3 8

Emergence of the novel pathogenic coronavirus SARS-CoV-2 and its rapid pandemic spread presents challenges that demand immediate attention. Here, we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA, and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in specific, sensitive and unbiased assay that complements the portfolio of SARS-CoV-2 serological assays. Sensitive, specific and quantitative serological assays are urgently needed for a better understanding of humoral immune response against the virus as a basis for developing public health strategies to control viral spread. The procedure described here has been used for clinical studies and provides a general framework for the application of quantitative high-throughput microscopy to rapidly develop serological assays for emerging virus infections.