Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell

Although SARS-CoV-2 infection requires hACE2 receptor for cell entry, a human H522 lung adenocarcinoma cell line that lacks hACE2 receptor was found to be susceptible for SARS-CoV-2 infection, but its cell entry was only permissive when viral spike protein has an E484D mutation. This infection is dependent on the existence of surface heparan sulfates in the H522 cells. Sera from vaccinated individuals efficiently blocked this hACE2-independent infection, whereas the inhibition was less effective when sera from convalescent patients of COVID-19 were used.