ABSTRACT
The novel HLA-DPA1*01:88 allele differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in Exon 3.
Subject(s)
HLA-DP alpha-Chains , High-Throughput Nucleotide Sequencing , Alleles , HLA-DP alpha-Chains/genetics , Histocompatibility Testing , HumansABSTRACT
The spread of SARS-CoV-2 has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges due to subsequent waves and long-term consequences of great concern. Here we charted the molecular basis of COVID-19 pathogenesis, by analysing patients immune response at single-cell resolution across disease course and severity. This approach uncovered cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identified a severity-associated activation of the receptor for advanced glycation endproduct (RAGE) pathway in monocytes. In vitro experiments confirmed that monocytes bind the SARS-CoV-2 S1-RBD via RAGE and that RAGE-Spike interactions drive monocyte infection. Our results demonstrate that RAGE is a novel functional receptor of SARS-CoV-2 contributing to COVID-19 severity. One-Sentence SummaryMonocyte SARS-CoV-2 infection via the receptor for advanced glycation endproduct triggers severe COVID-19.
