Supervised machine learning to support the diagnosis of bacterial infection in the context of COVID-19.

Background: Bacterial infection has been challenging to diagnose in patients with COVID-19. We developed and evaluated supervised machine learning algorithms to support the diagnosis of secondary bacterial infection in hospitalized patients during the COVID-19 pandemic.

Methods: Inpatient data at three London hospitals for the first COVD-19 wave in March and April 2020 were extracted.

Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study.

Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing.

Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing.

Background: To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection.

Methods: MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included.

Cytotoxic mediators in paradoxical HIV-tuberculosis immune reconstitution inflammatory syndrome.

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates combined antiretroviral therapy and antituberculosis therapy in HIV-1-coinfected tuberculosis patients. The immunopathological mechanisms underlying TB-IRIS are incompletely defined, and improved understanding is required to derive new treatments and to reduce associated morbidity and mortality. We performed longitudinal and cross-sectional analyses of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB-coinfected patients commencing antiretroviral therapy who did not develop TB-IRIS).

Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome.

The HIV-TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) can complicate combined treatments for HIV-1 and TB. Little is known about tissue damage in TB-IRIS. Matrix metalloproteinases (MMPs) degrade components of the extracellular matrix and consequently may play a role in such immunopathology.

Role of the interleukin 10 family of cytokines in patients with immune reconstitution inflammatory syndrome associated with HIV infection and tuberculosis.

Background: The interleukin 10 (IL-10) family comprises cytokines structurally related to IL-10 that share signaling receptors that have conserved signaling cascades. The immunopathogenesis of immune reconstitution inflammatory syndrome (IRIS) in patients with human immunodeficiency virus (HIV) infection and tuberculosis remains incompletely understood. We hypothesized that a deficiency of IL-10 and its homologs may contribute to the immunopathology of IRIS in these patients.

Relationship between chemokine receptor expression, chemokine levels and HIV-1 replication in the lungs of persons exposed to Mycobacterium tuberculosis.

Increased susceptibility to tuberculosis following HIV-1 seroconversion contributes significantly to the tuberculosis epidemic in sub-Saharan Africa. Lung-specific mechanisms underlying the interaction between HIV-1 and Mycobacterium tuberculosis infection are incompletely understood. Here we address these questions by examining the effect of HIV-1 and latent M.

Altered ratio of IFN-γ/IL-10 in patients with drug resistant Mycobacterium tuberculosis and HIV- Tuberculosis Immune Reconstitution Inflammatory Syndrome.

We have described a clinical relationship between HIV-Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) and anti-tubercular drug resistance. Here we studied the immune response of TB-IRIS patients from whom a drug-resistant (n = 11) or drug-susceptible (n = 25) Mycobacterium tuberculosis (MTB) strain was isolated after presenting with TB-IRIS. ELISpot analysis and multiplex cytokine analysis of the supernatant collected from peripheral blood mononuclear cells stimulated overnight with the heat-killed H37Rv MTB laboratory strain was used.

Corticosteroid-modulated immune activation in the tuberculosis immune reconstitution inflammatory syndrome.

Rationale: HIV-tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an immunopathological reaction to mycobacterial antigens induced by antiretroviral therapy. Prednisone reduces morbidity in TB-IRIS, but the mechanisms are unclear.

Objectives: To determine the effect of prednisone on the inflammatory response in TB-IRIS (antigen-specific effector T cells, cytokines, and chemokines).

Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome.

Increased access to combination antiretroviral therapy in areas co-endemic for tuberculosis (TB) and HIV-1 infection is associated with an increased incidence of immune reconstitution inflammatory syndrome (TB-IRIS) whose cause is poorly understood. A case-control analysis of pro- and anti-inflammatory cytokines in TB-IRIS patients sampled at clinical presentation, and similar control patients with HIV-TB prescribed combined antiretroviral therapy who did not develop TB-IRIS. Peripheral blood mononuclear cells were cultured in the presence or absence of heat-killed Mycobacterium tuberculosis for 6 and 24 h.

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls.

1alpha,25-dihydroxyvitamin D3 inhibits matrix metalloproteinases induced by Mycobacterium tuberculosis infection.

Matrix metalloproteinases (MMP) can degrade all components of pulmonary extracellular matrix. Mycobacterium tuberculosis induces production of a number of these enzymes by human macrophages, and these are implicated in the pathogenesis of pulmonary cavitation in tuberculosis. The active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], has previously been reported to inhibit secretion of MMP-9 in human monocytes (MN), but its influence on the secretion and gene expression of MMP and tissue inhibitors of MMP (TIMP) in M.

Type 1 helper T cells and FoxP3-positive T cells in HIV-tuberculosis-associated immune reconstitution inflammatory syndrome.

Rationale: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) induced by combination antiretroviral therapy (cART) has been attributed to dysregulated expansion of tuberculin PPD-specific IFN-gamma-secreting CD4(+) T cells.

Objectives: To investigate the role of type 1 helper T cell expansions and regulatory T cells in HIV-TB IRIS.

Methods: Longitudinal and cross-sectional studies of Mycobacterium tuberculosis-specific IFN-gamma enzyme-linked immunospot responses and flow cytometric analysis of blood cells from a total of 129 adults with HIV-1-associated tuberculosis, 98 of whom were prescribed cART.

IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37.

Vitamin D deficiency is associated with susceptibility to tuberculosis, and its biologically active metabolite, 1alpha,25 dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), has pleiotropic immune effects. The mechanisms by which 1alpha,25(OH)(2)D(3) protects against tuberculosis are incompletely understood. 1alpha,25(OH)(2)D(3) reduced the growth of mycobacteria in infected human PBMC cultures in a dose-dependent fashion.