Patients with severe COVID-19 exhibit marked lymphopenia. This preprint by Feng et al. used immunohistochemistry and immunofluorescence to characterize hilar and subscapular lymph nodes and spleens post-mortem from six patients who died from COVID-19. In addition to splenic and lymph node atrophy and necrosis, the authors reported significant lymphocytic apoptosis. Of note, ACE2-expressing CD68+CD169+ macrophages were detected in the splenic marginal zone and in marginal sinuses of lymph nodes, and these macrophages contained SARS-CoV-2 nucleoprotein antigen and showed upregulation of IL-6. Virally infected tissues also showed higher expression of FAS. This suggests that CD169+ macrophages could contribute to viral spread, excessive inflammation and activation-induced lymphocytic cell death during SARS-CoV-2 infection.