Emerging studies from SARS-CoV-2-infected patients indicate a preponderant role of monocytes/macrophages in the pathogenesis of this viral infection, in a similar way to that previously observed in other coronavirus outbreaks (SARS and MERS). The clinical presentation of severe patients resembles viral-associated hemophagocytic syndrome, a rare condition previously seen during lethal influenza pandemics and during previous SARS and MERS coronavirus outbreaks. SARS-CoV-2 infection triggers an over-exuberant inflammatory response due to the development of a cytokine storm and the depletion of the adaptative immune compartment, which may prelude sepsis in many cases. The present review summarizes past evidence on the role of monocytes/macrophages in previous coronavirus outbreaks and the emerging knowledge on their role in COVID-19 pathogenesis. Treatment strategies incorporating the blockade of migration and differentiation of monocyte-macrophage, such as granulocyte macrophage-colony stimulating factor inhibitors, might enhance the promising results seen so far with selective cytokine blockade.

Jose Gomez-Rial reports personal fees from and being a speaker in scientific meetings and advisor for Merck Sharp and Dohme, GlaxoSmithkline, and Pfizer, outside the submitted work. Irene Rivero-Calle reports trials fees paid to the institution from Ablynx, Jansen, and Mediummune, grants, personal fees, other from GSK, grants and personal fees (research grants and honoraria as an advisor and speaker, and for attending conferences and practical courses; trials fees paid to the institution) from Pfizer, MSD, Sanofi Pasteur, outside the submitted work. Federico Martinón-Torres has received honoraria from GSK, Pfizer, Sanofi Pasteur, MSD, Seqirus, and Janssen for taking part in advisory boards and expert meetings, and for acting as speaker in congresses outside the scope of the submitted work. FM-T has also acted as principal investigator in RCTs of the above-mentioned companies as well as Ablynx, Regeneron, Roche, Abbott, Novavax, and MedImmune, with honoraria paid to his institution. The authors report no other possible conflicts of interest in this work.