Unique molecular signatures sustained in circulating monocytes and regulatory T cells in convalescent COVID-19 patients.
Abstract
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, |
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Journal: | Clin Immunol;2023May05 109634. doi:10.1016/j.clim.2023.109634 |
Year: | 2023 |
PubMed: | PMID: 37150240 (Go to PubMed) |