Evolution of Blood Innate Immune Cell Phenotypes Following SARS-CoV-2 Infection in Hospitalized Patients with COVID-19

Innate immune cells appear to have an important implication in the resolution and/or the aggravation of COVID-19 pathogenesis after infection with SARS-CoV-2. To better appreciate the role of these cells during COVID-19, changes in blood eosinophil, neutrophil and monocyte count, and levels of surface protein markers have been reported. However, analyses at several timepoints of multiple surface markers on granulocytes and monocytes over a period of one month after SARS-CoV-2 infection, are missing. Therefore, in this study, we performed blood eosinophil, neutrophil and monocyte phenotyping using a list of surface proteins and flow cytometry during a period of 30 days after hospitalization of patients with severe SARS-CoV-2 infection. Blood cell counts were reported at seven different timepoints over the 30 day-period as well as measures of multiple mediators in serum using a targeted multiplex assay approach. Our results indicate rapid and important recruitment of blood eosinophils to tissue and a phenotype defined as CD69/CD63/CD125high and CCR3/CD44low during the early phases of hospitalization. Conversely, neutrophil count increased during later timepoints when also neutrophils displayed an immature, activated and immunosuppressive phenotype (i.e., elevated percentage of CD10/CD16low, CD10lowCD177high, CD11bhighCD62Llow, CD16highCD62Llow), corroborated by enhanced serum proteins that are markers of neutrophil activation. Finally, our results suggest a rapid recruitment of non-classical monocytes leaving CD163/CD64/CD32high monocytes in circulation during the very early phase. In conclusion, our study reveals potential very early roles for eosinophils and monocytes in the pathogenesis of COVID-19 with likely reprogramming of eosinophils in the bone marrow. The exact roles of the pro-inflammatory neutrophils, and the functions of the eosinophils and the monocytes as well as these innate immune cell-types interplays need to be further investigated.