Lymphopenia and systemic viral dissemination are commonly found in severe COVID-19. This preprint study reports that immune cells (monocytes, CD4+ T cells, CD8+ T cells and B cells) are susceptible to SARS-CoV-2 infection. This was observed by in vitro infection of immune cells and by ex vivo detection of SARS-CoV-2 in peripheral blood mononuclear cells from patients with severe COVID-19. Post-mortem in situ analysis of lung tissues further confirmed the presence of infected immune cells in COVID-19. As monocytes and lymphocytes do not express ACE2, it remains to be seen whether the virus uses an alternative entry strategy and whether circulating infected immune cells contribute to viral spread and COVID-19 disease progression.