Current hotspot and study trend of innate immunity in COVID-19: a bibliometric analysis from 2020 to 2022.

Background: Since the coronavirus disease 2019 (COVID-19) has spread throughout the world, many studies on innate immunity in COVID-19 have been published, and great progress has been achieved, while bibliometric analysis on hotspots and research trends in this field remains lacking. Methods: On 17 November 2022, articles and reviews on innate immunity in COVID-19 were recruited from the Web of Science Core Collection (WoSCC) database after papers irrelevant to COVID-19 were further excluded. The number of annual publications and the average citations per paper were analyzed by Microsoft Excel. Bibliometric analysis and visualization of the most prolific contributors and hotspots in the field were performed by VOSviewer and CiteSpace software. Results: There were 1,280 publications that met the search strategy on innate immunity in COVID-19 and were published from 1 January 2020 to 31 October 2022. Nine hundred thirteen articles and reviews were included in the final analysis. The USA had the highest number of publications (Np) at 276 and number of citations without self-citations (Nc) at 7,085, as well as an H-index of 42, which contributed 30.23% of the total publications, followed by China (Np: 135, Nc: 4,798, and H-index: 23) with 14.79% contribution. Regarding Np for authors, Netea, Mihai G. (Np: 7) from the Netherlands was the most productive author, followed by Joosten, Leo A. B. (Np: 6) and Lu, Kuo-Cheng (Np: 6). The Udice French Research Universities had the most publications (Np: 31, Nc: 2,071, H-index: 13), with an average citation number (ACN) at 67. The journal Frontiers in Immunology possessed the most publications (Np: 89, Nc: 1,097, ACN: 12.52). "Evasion" (strength 1.76, 2021-2022), "neutralizing antibody" (strength 1.76, 2021-2022), "messenger RNA" (strength 1.76, 2021-2022), "mitochondrial DNA" (strength 1.51, 2021-2022), "respiratory infection" (strength 1.51, 2021-2022), and "toll-like receptors" (strength 1.51, 2021-2022) were the emerging keywords in this field. Conclusion: The study on innate immunity in COVID-19 is a hot topic. The USA was the most productive and influential country in this field, followed by China. The journal with the most publications was Frontiers in Immunology. "Messenger RNA," "mitochondrial DNA," and "toll-like receptors" are the current hotspots and potential targets in future research.

Brain motor and fear circuits regulate leukocytes during acute stress.

The nervous and immune systems are intricately linked1. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood2. Here we show that distinct brain regions shape leukocyte distribution and function throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that motor circuits induce rapid neutrophil mobilization from the bone marrow to peripheral tissues through skeletal-muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow through direct, cell-intrinsic glucocorticoid signalling. These stress-induced, counter-directional, population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and directing their recruitment to sites of injury. On the other hand, corticotropin-releasing hormone neuron-mediated leukocyte shifts protect against the acquisition of autoimmunity, but impair immunity to SARS-CoV-2 and influenza infection. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, therefore calibrating the ability of the immune system to respond to physical threats.

Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity.

Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ingredients in the human body such as hyaluronic acid in the form of hyaluronic acid-glycine cholesterol (HACH) conjugate as an excipient for vaccine formulation. Interestingly, HACH grafted with ~13 wt.% cholesterol has good water dispersity and can serve as an emulsifier to stabilize the squalene/water interfaces, yielding a milky white and isotropic emulsion (SQ@HACH) after being passed through a high-shear microfluidizer. Our results show that SQ@HACH particles possessed a unimodal average hydrodynamic diameter of approximately 190 nm measured by dynamic light scattering and exhibited good stability upon storage at 4 °C and 37 °C for over 20 weeks. The results of immunogenicity using a mouse model with ovalbumin (OVA) as the antigen revealed that SQ@HACH significantly enhanced antigen-specific immune responses, including the polarization of IgG antibodies, the cytokine secretions of T cells, and enhancement of cytotoxic T lymphocyte (CTL) activation. Moreover, SQ@HACH revealed lower local inflammation and rapidly absorbing properties compared with AlPO4 after intramuscular injection in vivo, indicating the potential functions of the HA-derived conjugate as an excipient in vaccine formulations for enhancement of T cell-mediated immunity.

Type I, II, and III Interferon Signatures Correspond to Coronavirus Disease 2019 Severity.

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients. Type III IFN responses were induced in the early phase of infection, even in convalescent patients. These results highlight the importance of early type I and III IFN responses in controlling coronavirus disease 2019 progression.

Qigong exercise enhances cognitive functions in the elderly via an interleukin-6-hippocampus pathway: A randomized active-controlled trial.

BACKGROUND: Evidence has suggested that exercise protects against cognitive decline in aging, but the recent lockdown measures associated with the COVID-19 pandemic have limited the opportunity for outdoor exercise. Herein we tested the effects of an indoor exercise, Qigong, on neurocognitive functioning as well as its potential neuro-immune pathway. METHODS: We conducted a 12-week randomized active-controlled trial with two study arms in cognitively healthy older people. We applied Wu Xing Ping Heng Gong (Qigong), which was designed by an experienced Daoist Qigong master, to the experimental group, whereas we applied the physical stretching exercise to the control group. The Qigong exercise consisted of a range of movements involving the stretching of arms and legs, the turning of the torso, and relaxing, which would follow the fundamental principles of Daoism and traditional Chinese medicine (e.g., Qi). We measured aging-sensitive neurocognitive abilities, serum interleukin-6 (IL-6) levels, and brain structural volumes in the experimental (Qigong, n = 22) and control groups (stretching, n = 26) before and after the 12-week training. RESULTS: We observed that Qigong caused significant improvement in processing speed (t (46) = 2.03, p = 0.048) and sustained attention (t (46) = -2.34, p = 0.023), increased hippocampal volume (t (41) = 3.94, p < 0.001), and reduced peripheral IL-6 levels (t (46) = -3.17, p = 0.003). Moreover, following Qigong training, greater reduction of peripheral IL-6 levels was associated with a greater increase of processing speed performance (bootstrapping CI: [0.16, 3.30]) and a more significant training-induced effect of hippocampal volume on the improvement in sustained attention (bootstrapping CI: [-0.35, -0.004]). CONCLUSION: Overall, these findings offer significant insight into the mechanistic role of peripheral IL-6-and its intricate interplay with neural processes-in the beneficial neurocognitive effects of Qigong. The findings have profound implications for early identification and intervention of older individuals vulnerable to cognitive decline, focusing on the neuro-immune pathway. The trial was registered at clinicaltrials.gov (identifier: NCT04641429).

Type I, II, and III interferon signatures correspond to COVID-19 disease severity (preprint)

We analyzed the plasma levels of interferons and cytokines, and the expression of interferon-stimulated genes in peripheral blood mononuclear cells in COVID-19 patients with different disease severity. Mild patients exhibited transient type I interferon responses, while ICU patients had prolonged type I interferon responses with hyper-inflammation mediated by interferon regulatory factor 1. Type II interferon responses were compromised in ICU patients. Type III interferon responses were induced in the early phase of SARS-CoV-2 infection, even in convalescent patients. These results highlight the importance of type I and III interferon responses during the early phase of infection in controlling COVID-19 progression.