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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03. 24.20042655 doi: medRxiv preprint responses and monocyte/macrophage and neutrophil accumulation. 11 They highlighted that both SARS-CoV and MERS-CoV encode multiple proteins that antagonize IFN responses and that an early antagonism of the IFN response might delay or evade the innate immune response. 11,12 They concluded that delayed IFN signaling could further orchestrate inflammatory monocyte/macrophage responses and sensitize T cells to apoptosis resulting in a further dysregulated inflammatory response. 12 These inflammatory macrophages accumulate in the lungs and are the likely source of pro-inflammatory cytokines and chemokines associated with fatal disease induced by human coronavirus infections, such as SARS and COVID-19. Autopsy findings from patients with COVID-19 mirror these findings. 13 Interestingly, as we confirmed, monocytes in infected patients are ACE2 positive. Since ACE2 is the receptor used by COVID-19 to gain entry to cells, this suggests the possibility that monocytes in patients with COVID-19 may be directly infected by COVID-19, leading to abortive replication and a delayed type I IFN response in these cells. 12 Indeed, the SARS-CoV virus has been found to infect monocytes, though replication was poor. 14 Infection of monocytes by SARS-CoV was associated with inflammatory activation and alterations in immune function-related gene expression. 15, 16 Inflammatory cytokines such as IFN-α, GM-CSF, IL-6 or TNF-α can also stimulate the differentiation of monocytes to macrophages.