COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome

Dan Zhang; Rui Guo; Lei Lei; Hongjuan Liu; Yawen Wang; Yili Wang; Tongxin Dai; Tianxiao Zhang; Yanjun Lai; Jingya Wang; Zhiqiang Liu; Aili He; Michael O'Dwyer; Jinsong Hu

Similar to our findings, Zhou and colleagues recently reported on the presence of a significantly higher percentage of CD14 + CD16 + inflammatory monocytes in the peripheral blood of COVID-19 patients compared to normal healthy controls. 17, 18 They also reported that the percentage of CD14 + CD16 + monocytes was much higher in severe pulmonary syndrome patients from ICU. They also showed that these monocytes had the capability of secreting GM-CSF and similar to our findings could also secrete IL-6, which was higher in ICU patients, in association with cytokine storm. They described a model whereby an abnormal TH1 response triggers GM-CSF induced monocyte/macrophage activation leading to an increase in IL-6 producing CD14 + CD16 + monocytes, which migrate to the lungs and induce subsequent lung damage along with an inflammatory cytokine storm. This is also supported by recent data relating to single cell RNA sequencing of immune cells from bronchoalveolar lavage samples of patients with COVID-19, which provide important insights into the immune microenvironment of COVID-19 infected lungs. 19 These data show that Ficolin 1 expressing monocyte-derived macrophages, supplant fatty acid binding protein-4 (FABP4) expressing alveolar macrophages as the predominant macrophage subset in the lungs of patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Based on these data, a pilot trial of Tociluzumab, an IL-6 receptor antibody approved for treatment of Rheumatoid Arthritis as well as CAR-T associated cytokine release syndrome was recently conducted in a small number of severe COVID-19 patients with promising results. [20] [21] [22] Other treatments for cytokine storm, such as the interleukin-1 (IL-1) receptor antagonist Anakinra and the Janus kinase (JAK) inhibitors may also prove to be useful, though to date there is little or no clinical experience with these agents in treating COVID-19. [23] [24] [25] Given the central role that monocytes appear to play in COVID-19 infection it is important to recognise the limited information provided by most routine automated blood analyzers. Indeed, the contribution of monocytes to the patient's pathology may be overlooked as patients with severe disease can be monocytopenic. 5 This may well reflect migration of the inflammatory monocyte/macrophages All rights reserved. No reuse allowed without permission.