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Chest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Here, the authors present a multinational study on the application of deep learning algorithms for COVID-19 diagnosis against multiple lung conditions as controls.

The fungus growing termite species Macrotermes bellicosus (M. bellicosus) is used in nutrition and traditional medicine in the Republic of Benin for the treatment of infectious and inflammatory diseases. Previous findings demonstrated evidence of anti-inflammatory and spasmolytic properties of M. bellicosus. The aim of the present study was to evaluate the antimicrobial potential of different extracts of M. bellicosus samples and determine the chemical profile of an ethanolic M. bellicosus extract. Chemical profiling was conducted using centrifugal partition chromatography and 13C-NMR, followed by MALDI-TOF MS. Major identified compounds include hydroquinone (HQ), methylhydroquinone (MHQ), 3,4-dihydroxyphenethyl glycol (DHPG), N-acetyldopamine (NADA) and niacinamide. The fatty acid mixture of the extract was mainly composed of linoleic and oleic acid and highlights the nutritional purpose of M. bellicosus. Using the Kirby–Bauer disc diffusion and broth microdilution assay, an antibacterial activity of M. bellicosus samples was observed against various clinical strains with a highest growth inhibition of S. aureus. In addition, HQ and MHQ as well as fractions containing DHPG, niacinamide and NADA inhibited S. aureus growth. The reported antimicrobial activity of M. bellicosus and identified active substances provide a rationale for the traditional medicinal use of M. bellicosus.

Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.

The herbal preparation coffee charcoal is produced by over-roasting and milling green dried Coffea arabica L. seeds, and has a long-standing tradition in the treatment of inflammatory and gastrointestinal disorders. Its therapeutic properties are commonly attributed to adsorptive and astringent effects. This insufficiently explains its mode of action, especially when used in the treatment of inflammatory diseases in lower dosages. Our investigations aimed to identify bioactive secondary plant metabolites affecting cytokine-signaling. Thus, a phytochemical analysis of coffee charcoal extract was conducted using HPLC and LC/MS. Trigonelline, neochlorogenic acid, chlorogenic acid, caffeine, cryptochlorogenic acid, feruloylquinic acid isomers, and a caffeoylquinolacton were identified in the extract. Subsequently, the effects of coffee charcoal extract, chlorogenic acid isomers, their metabolite caffeic acid, caffeine, and trigonelline on cytokine (TNF, IL-6, MCP-1) release from LPS-challenged human THP-1 macrophages were examined to evaluate anti-inflammatory activity. Coffee charcoal showed concentration-dependent mild-to-medium inhibitory effects. The chlorogenic acid isomers and caffeic acid inhibited the TNF release, with cryptochlorogenic acid exerting the most distinct effects, as well as decreasing the release of IL-6 and MCP-1. In addition, scanning electron microscopic images provided an impression of the particle constitution, indicating a larger particle size and less structured surface of coffee charcoal in comparison to activated charcoal. In conclusion, our findings underline that beyond adsorptive effects, coffee charcoal exhibits pharmacological properties, which derive from a spectrum of secondary plant metabolites and support the therapeutic use in inflammatory diseases. Chlorogenic acids, particularly cryptochlorogenic acid, appear as pivotal bioactive compounds.

The fungus Cryptococcus is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-γ as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell damage.