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Globally, the COVID-19 pandemic has had extreme consequences for the healthcare system and calls for diagnostic tools to monitor and understand the transmission, pathogenesis and epidemiology, as well as to evaluate future vaccination strategies.
Here we have developed novel flexible ELISA-based assays for specific detection of SARS-CoV-2 antibodies against the receptor-binding domain (RBD): An antigen sandwich-ELISA relevant for large population screening and three isotype-specific assays for in-depth diagnostics. Their performance was evaluated in a cohort of 350 convalescent participants with previous COVID-19 infection, ranging from asymptomatic to critical cases. We mapped the antibody responses to different areas on protein N and S and showed that the IgM, A and G antibody responses against RBD are significantly correlated to the disease severity. These assays-and the data generated from them-are highly relevant for diagnostics and prognostics and contribute to the understanding of long-term COVID-19 immunity.
Our findings provide support to the notion that antibodies towards SARS-CoV-2 represent a double-edged sword. Antibodies are important in viral neutralization, but also in Fc receptor-mediated phagocytosis, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDCC) and subsequent elimination of pathogens. However, it is known that particularly ADCC and CDCC can drive harmful and systemic pro-inflammatory responses that can have severe pathophysiological consequences. Thus, based on our findings and others, it may be suggested that an unwanted immune response towards SARS-CoV-2 may be one of the mechanisms causing hyperactivation of macrophages and monocytes, leading to the deadly cytokine storm, which seems to be a hallmark of COVID-19
Preprint of the study available at medRxiv (July 29, 2020):
