Human monocytes exposed to SARS-CoV-2 display features of innate immune memory producing high levels of CXCL10 upon restimulation

Introduction A role for innate immune memory in protection during COVID-19 infection or vaccination has been recently reported. However, no study so far has shown whether SARS-CoV-2 can train innate immune cells. The aim of this study was to investigate whether this virus can induce trained immunity in human monocytes.Methods Monocytes were exposed to inactivated (i)SARS-CoV-2 for 24 hours, followed by a resting period in medium only and a secondary stimulation on day 6 after which, the cytokine/chemokine and transcriptomic profiles were determined.Results Compared to untrained cells, the iSARS-CoV-2-trained monocytes secreted significantly higher levels of IL-6, TNF-alpha, CXCL10, CXCL9 and CXCL11 upon restimulation. Transcriptome analysis of iSARS-CoV-2 trained monocytes revealed increased expression of several inflammatory genes. As epigenetic and metabolic modifications are hallmarks of trained immunity, we analyzed the expression of genes related to these processes. Findings indicate that indeed SARS-CoV-2-trained monocytes show changes in the expression of genes involved in metabolic pathways including the tricarboxylic acid (TCA) cycle, amino acid metabolism and the expression of several epigenetic regulator genes. Using epigenetic inhibitors that block histone methyl and acetyl transferases, we observed that the capacity of monocytes to be trained by iSARS-CoV-2 was abolished.Conclusion Overall, our findings indicate that iSARS-CoV-2 can induce properties associated with trained immunity in human monocytes. These results contribute to the knowledge required for improving vaccination strategies to prevent infectious diseases.