et al. (2020). Co-infections of SARS-CoV-2 with multiple common respiratory pathogens in infected patients. Sci China Life Sci 63, 606-609. https://doi.

Background: Tuberculosis (TB) continues to be a critical global health problem, which killed millions of lives each year. Certain circulating cell subsets are thought to differentially modulate the host immune response towards Mycobacterium tuberculosis (Mtb) infection, but the nature and function of these subsets is unclear. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from healthy controls (HC), latent tuberculosis infection (LTBI) and active tuberculosis (TB) and then subjected to single-cell RNA sequencing (scRNA-seq) using 10 £ Genomics platform. Unsupervised clustering of the cells based on the gene expression profiles using the Seurat package and passed to tSNE for clustering visualization. Flow cytometry was used to validate the subsets identified by scRNA-Seq. Findings: Cluster analysis based on differential gene expression revealed both known and novel markers for all main PBMC cell types and delineated 29 cell subsets. By comparing the scRNA-seq datasets from HC, LTBI and TB, we found that infection changes the frequency of immune-cell subsets in TB. Specifically, we observed gradual depletion of a natural killer (NK) cell subset (CD3-CD7+GZMB+) from HC, to LTBI and TB. We further verified that the depletion of CD3-CD7+GZMB+ subset in TB and found an increase in this subset frequency after anti-TB treatment. Finally, we confirmed that changes in this subset frequency can distinguish patients with TB from LTBI and HC. Interpretation: We propose that the frequency of CD3-CD7+GZMB+ in peripheral blood could be used as a novel biomarker for distinguishing TB from LTBI and HC.

19The ongoing SARS-CoV-2 outbreak has killed over twenty-one thousand and sickened over four 20 hundred thousand people worldwide, posing a great challenge to global public health. A sensitive and 21 accurate diagnosis method will substantially help to control disease expansion. Here, we developed a 22 chemiluminescence-immunoassay method based on the recombinant nucleocapsid antigen and the 23 magnetic beads for diagnosis of SARS-CoV-2 infections and surveillance of antibody changing pattern. : medRxiv preprint Serums from 29 healthy individuals, 51 tuberculosis patients, and 79 SARS-CoV-2 confirmed patients 25 were employed to evaluate the performance of this approach. Compared to the IgM testing, the IgG 26 testing was more reliable in which it identified 65 SARS-CoV-2 infections from the 79 confirmed 27 patients and only two false-positive cases from the 80 control group with a sensitivity and specificity 28 reaching 82.28% and 97.5%, respectively. However, only a slight difference (not statistically 29 significant) in the detected cases of SARS-CoV-2 infections was observed between the IgM and IgG 30 testing manner in patients at a different time of onset of disease. A performance comparison 31 between an ELISA kit using the same nucleocapsid antigen and our chemiluminescence method was 32 undertaken. The same false-positive cases were seen in both methods from the paired control group, 33 while ELISA kit can only detect half of the SARS-CoV-2 infections from paired SARS-CoV-2 confirmed 34 patients group than that of the chemiluminescence method, indicating a higher performance for the 35 chemiluminescence-immunoassay approach. Together, our studies provide a useful and valuable 36 serological testing tool for the diagnosis of SARS-CoV-2 infections in the community.37

We developed a chemiluminescence immunoassay method based on the recombinant nucleocapsid antigen and assessed its performance for the clinical diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections by detecting SARS-CoV-2-specific IgM and IgG antibodies in patients. Full-length recombinant nucleocapsid antigen and tosyl magnetic beads were used to develop the chemiluminescence immunoassay approach. Plasmas from 29 healthy cohorts, 51 tuberculosis patients, and 79 confirmed SARS-CoV-2 patients were employed to evaluate the chemiluminescence immunoassay method performance for the clinical diagnosis of SARS-CoV-2 infections. A commercial ELISA kit (Darui Biotech, China) using the same nucleocapsid antigen was used for the in-parallel comparison with our chemiluminescence immunoassay method. The IgM and IgG manner of testing in the chemiluminescence immunoassay method showed a sensitivity and specificity of 60.76% (95% CI 49.1 to 71.6) and 92.25% (95% CI 83.4 to 97.2) and 82.28% (95% CI 72.1 to 90.0) and 97.5% (95% CI 91.3 to 99.7), respectively. Higher sensitivity and specificity were observed in the chemiluminescence immunoassay method compared with the Darui Biotech ELISA kit. The developed high sensitivity and specificity chemiluminescence immunoassay IgG testing method combined with the RT-PCR approach can improve the clinical diagnosis for SARS-CoV-2 infections and thus contribute to the control of COVID-19 expansion.

Regulatory B cells (Bregs) are a subset of B cells, which reportedly exert significant immunomodulatory effects through the production of interleukin (IL)-10, IL-35 and transforming growth factor-β. Over the last decade, studies have indicated that Bregs function in autoimmune and allergic diseases through antigen-specific and non-specific immunoregulatory mechanisms. However, only a limited number of reviews have focused on the role of Bregs during infection, particularly their functions in intracellular infections. The present review discusses the role of Bregs in infectious diseases in animal models and human studies, and provides an overview of the immunoregulatory mechanisms used by Bregs.

BackgroundPerturbed iron homeostasis is a risk factor for tuberculosis (TB) progression and an indicator of TB treatment failure and mortality. Few studies have evaluated iron homeostasis as a TB diagnostic biomarker.MethodsWe recruited participants with TB, latent TB infection (LTBI), cured TB (RxTB), pneumonia (PN) and healthy controls (HCs). We measured serum levels of three iron biomarkers including serum iron, ferritin and transferrin, then established and validated our prediction model.ResultsWe observed and verified that the three iron biomarker levels correlated with patient status (TB, HC, LTBI, RxTB or PN) and with the degree of lung damage and bacillary load in patients with TB. We then built a TB prediction model, neural network (NNET), incorporating the data of the three iron biomarkers. The model showed good performance for diagnosis of TB, with 83% (95% CI 77 to 87) sensitivity and 86% (95% CI 83 to 89) specificity in the training data set (n=663) and 70% (95% CI 58 to 79) sensitivity and 92% (95% CI 86 to 96) specificity in the test data set (n=220). The area under the curves (AUCs) of the NNET model to discriminate TB from HC, LTBI, RxTB and PN were all >0.83. Independent validation of the NNET model in a separate cohort (n=967) produced an AUC of 0.88 (95% CI 0.85 to 0.91) with 74% (95% CI 71 to 77) sensitivity and 92% (95% CI 87 to 96) specificity.ConclusionsThe established NNET TB prediction model discriminated TB from HC, LTBI, RxTB and PN in a large cohort of patients. This diagnostic assay may augment current TB diagnostics.

Prospective studies have suggested that some individuals have a persistent IgM response to Mycoplasma pneumoniae infection with relatively little IgG production over many months. Persistence of the organism in patients with an allergic phenotype might predispose to the development of asthma. This study was designed to analyze the prevalence of M. pneumoniae infection and the immune response to that infection among children with asthma compared with controls. A prospective study was performed in 82 children with physician-diagnosed asthma and 98 nonasthmatic controls over a 5-year period comparing them for evidence of current or prior infection by M. pneumoniae using serology (IgG and IgM), culture, and polymerase chain reaction (PCR), and in vitro cellular responses to M. pneumoniae antigen. Similar numbers of controls (9/98) and asthmatic children (6/82) were PCR(+) for M. pneumoniae at some time during the study. IgM antibody to M. pneumoniae was detected in similar numbers of controls (21/98) and asthmatic children (18/82), but positive IgG antibody titers were detected in significantly more controls (13/98) than asthmatic children (3/82; p = 0.03). Similar numbers from each group were IgM(+) on more than one annual visit (9/98 controls and 7/82 asthmatic children). Antigen-driven proliferation and interferon (IFN) gamma production by mononuclear cells from IgM(+) controls were significantly greater than that of IgM(-) controls, but there was no difference in proliferation and IFN-gamma production by cells from IgM(+) and IgM(-) asthmatic children. These results suggest that asthmatic children have deficient cellular and humoral responses to M. pneumoniae infection compared with nonasthmatic controls.

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