Concerning the role of macrophages in COVID-19, the presence of ACE2-expressing CD68+CD169+ macrophages containing SARS-CoV-2 nucleoprotein antigen and showing an increased release of IL-6 was observed in infected spleen and lymph nodes.100 Notably, immunohistochemical and immunofluorescence analyses of lymph nodes and spleen tissue from autopsy samples of patients who died from COVID-19 revealed lymphocytic apoptosis. The tissues infected by SARS-CoV-2 also showed an upregulated expression of Fas, suggesting a role for CD169+ macrophages in viral spreading, aberrant inflammation, and activation-induced lymphocyte apoptosis. Moreover, histological examinations of biopsy samples of patients who died from COVID-19 revealed an increased alveolar exudate due to the extended neutrophil and monocyte infiltrate in lung capillaries with fibrin deposition, probably leading to difficulties in gas exchange. Through nanomedicine, we envision therapeutic approaches aimed at targeting specific immune subpopulations to avoid these complications, and different nanomaterials have already been explored for their specific impact on different immune cell subpopulations.82,83,86 Octadecylamine-functionalized and dexamethasone-adsorbed nanodiamond promotes anti-inflammatory and proregenerative behavior in human macrophages in vitro.101 A low dose of this functionalized nanodiamond also reduced macrophage infiltration and expression of proinflammatory mediators iNOS and tumor necrosis factor (TNF)-α in mice. Overall, these results suggest that nanodiamond particles may be useful as an inherently immunomodulatory platform.