Human monocytes exposed to SARS-CoV-2 display features of trained immunity producing high levels of CXCL10 upon restimulation

The capacity of innate immune cells to build immunological memory after a first encounter with certain pathogens or vaccines that allow them to respond stronger to reinfection is referred to as “trained immunity”. Despite few studies highlighting an important role for trained immunity in protection during COVID-19 infection or vaccination, no study so far has shown whether SARS-CoV-2 can train innate immune cells to respond stronger to a second stimuli. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes. To this purpose we used monocytes from healthy donors and exposed them to inactivated (i) SARS -CoV-2 for 24 hours followed by a resting period of several days in medium only and restimulation on day 6. On day 6, to evaluate the effects of iSARS-CoV-2 training on monocyte gene expression, transcriptomic analysis of human monocytes, before or 3h after LPS stimulation, was done. Our data provide the transcriptional profile of untrained and trained monocytes with iSARS-CoV-2. Overall design: The transcriptomic profile of iSARS-CoV-2 trained and untrained monocytes prior and post-secondary LPS stimulation was investigated. Comparisons were made for four groups namely, untrained monocytes in medium only (Unt-Med); untrained monocytes stimulated with LPS on day 6 (Unt-LPS); trained monocytes with iSARS-CoV-2 without LPS stimulation on day 6 (Trn_S-Med) and iSARS-CoV-2-trained monocytes stimulated with LPS on day 6 (Trn_S-LPS).