ACE2-independent SARS-CoV-2 virus entry through cell surface GRP78 on monocytes - evidence from a translational clinical and experimental approach

SARS-CoV-2 infects host cells via an ACE2/TMPRSS2 entry mechanism. Monocytes and macrophages, which play a key role during severe COVID-19 express only low or no ACE2, suggesting alternative entry mechanisms in these cells. In silico analyses predicted GRP78, which is constitutively expressed on monocytes and macrophages, to be a potential candidate receptor for SARS-CoV-2 virus entry. To confirm the hypothesis, we conducted high-throughput RNA sequence to characterize the role of GRP78 in monocytes function in COVID-19 patients We then performed gene expression profiling analysis using data obtained from RNA-seq of separated primary monocytes from 4 healthy controls and 4 COVID-19 patients Comparative gene expression profiling analysis of RNA-seq data for separated monocytes from 4 healthy controls and 4 COVID-19 patients