Single-cell transcriptomic analysis reveals a systemic immune dysregulation in COVID-19-associated pediatric encephalopathy

Abstract

Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments. Here, we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy. We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy, especially those with acute necrotizing encephalopathy (AE). This was characterized a marked reduction of various lymphocytes (e.g., CD8+ T and CD4+ T cells) and significant increases in other inflammatory cells (e.g., monocytes). Further analysis revealed activation of multiple cell apoptosis pathways (e.g., granzyme/perforin-, FAS- and TNF-induced apoptosis) may be responsible for lymphopenia. A systemic S100A12 upregulation, primarily from classical monocytes, may have contributed to cytokine storms in patients with AE. A dysregulated type I interferon (IFN) response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE. In COVID-19 patients with AE, myeloid cells (e.g., monocytic myeloid-derived suppressor cells) were the likely contributors to immune paralysis. Finally, the immune landscape in COVID-19 patients with encephalopathy, especially for AE, were also characterized by NK and T cells with widespread exhaustion, higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response. Taken together, this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments, especially for those with AE.

Rapid detection of monkeypox virus and differentiation of West African and Congo Basin strains using endonuclease restriction-mediated real-time PCR-based testing

“…Aer the global pandemic of COVID-19, requirements for the development and application of PCR-based methods, including specialized instruments, trained personnel and equipped laboratories, have been increasing around the world, even in rural regions, facilitating this technique being more available and widespread. 9,31 In this context, we developed a novel mode of real-time PCR method for the simultaneous detection of generic MPXV strains and the differentiation of its two clades in one reaction within a short time. This new real-time PCR method was devised based on a technique termed endonuclease restrictionmediated real-time polymerase chain reaction (ET-PCR), 32,33 which can overcome the limitations of conventional PCR and technical difficulties of real-time PCR with the restriction enzyme BstUI and a modied primer of conventional PCR.…”