The COVID-19 pandemic is an ongoing global challenge. It is a mild to moderate respiratory tract infection in most people but can cause life-threatening respiratory failure or persistent debilitating symptoms in a subset of patients.1 The mechanisms of protective immunity in mild cases and the pathogenesis of severe COVID-19 remain unclear. It has been proposed that the potent anti-inflammatory effects of corticosteroids like dexamethasone may decrease the fatality rate in severe COVID-19 patients2 but its specific mechanism is still not well understood.
In this observational, three-cohort study, Hyun-Woo Jeong and his team at Einocle Inc, Seoul, South Korea, performed a single-cell transcriptome analysis of peripheral blood mononuclear cells (PBMCs) study from three independent medical centers in South Korea. Using samples from 171 patients, they aimed to determine the changes in immune cell composition at the molecular level, over time and upon treatment with dexamethasone. They identified the up-regulated type I interferon response as a hyperinflammatory signature of severe COVID-19. They also observed that different sets of cytokines and growth factors were expressed during disease progression, either aggravating or improving responses by the various myeloid cell types.
Besides, they saw that the mammalian target of rapamycin (mTOR) signaling pathway was significantly upregulated in monocytes by dexamethasone treatment and propose that this may play a key role in the regulation of innate immune homeostasis and immunosuppression in severe COVID-19. The study demonstrates detailed insights into the immunopathogenesis of SARS-CoV-2 infection and reveals molecular and cellular characteristics of the peripheral immune system during disease progression and dexamethasone treatment in COVID-19 patients.
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