Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Unique molecular signatures sustained in circulating monocytes and regulatory T cells in convalescent COVID-19 patients.


Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including convalescent COVID-19 and sero-negative controls. Flow cytometry analyses revealed reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells within the patients who have recovered from severe COVID-19. sc-RNA seq analysis identifies seven heterogeneous clusters of monocytes and nine Treg clusters featuring distinct molecular signatures in association with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocytes and Tregs expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters featuring S100 family genes: one monocyte cluster of S100A8 & A9 coupled with high HLA-I and another cluster of S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, as well as a unique TGF-beta high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-lived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (>= 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.

Authors: Hoffmann AD, Weinberg SE, Swaminathan S, Chaudhuri S, Mubarak HF, Schipma MJ, Mao C, Wang X, El-Shennawy L, Dashzeveg NK, Wei J, Mehl PJ, Shihadah LJ, Wai CM, Ostiguin C, Jia Y, D'Amico P, Wang NR, Luo Y, Demonbreun AR, Ison MG, Liu H, Fang D,
Journal: Clin Immunol;2023May05 109634. doi:10.1016/j.clim.2023.109634
Year: 2023
PubMed: PMID: 37150240 (Go to PubMed)