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Background: Multisystem inflammatory syndrome in children (MIS-C) presents with inflammation and pathology of multiple organs in the pediatric population in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Methods: We characterized the SARS-CoV-2 antigen-specific cytokine and chemokine responses in children with MIS-C, coronavirus disease 2019 (COVID-19), and other infectious diseases.Results: MIS-C is characterized by elevated levels of type 1 (interferon-γ, interleukin [IL] 2), type 2 (IL-4, IL-13), type 17 (IL-17), and other proinflammatory cytokines (IL-1α, IL-6, IL-12p70, IL-18, and granulocyte-macrophage colony-stimulating factor) in comparison to COVID-19 and other infectious diseases following stimulation with SARS-CoV-2-specific antigens. Similarly, upon SARS-CoV-2 antigen stimulation, CCL2, CCL3, and CXCL10 chemokines were significantly elevated in children with MIS-C in comparison to the other 2 groups. Principal component analysis based on these cytokines and chemokines could clearly distinguish MIS-C from both COVID-19 and other infections. In addition, these responses were significantly diminished and normalized 6-9 months after recovery.Conclusions: Our data suggest that MIS-C is characterized by an enhanced production of cytokines and chemokines that may be associated with disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Covaxin/BBV152 is one of the most widely used vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and one of the few vaccines used extensively in low- and middle-income countries (LMIC).Methods: We investigated the effect of Covaxin on the SARS-CoV-2 specific IgG and IgA and neutralizing antibody (NAb) levels at baseline (M0) and at Months 1 (M1), 2 (M2), 3 (M3), 4 (M4), 6 (M6) and 12 (M12) following vaccination in healthcare workers. In addition, we also examined the NAb levels against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA), B.1.1.7 (Alpha, UK) and B.1.1.529 (Omicron).Results: Covaxin induces enhanced SARS-CoV-2 binding antibodies of IgG and IgA responses against both spike (S) and nucleocapsid (N) antigens at M1, M2, M3, M4, M6 and M12 in comparison with M0. Our data also reveal that NAb levels against the ancestral strain (Wuhan, wild type) are elevated and sustained at M1, M2, M3, M4, M6 and M12 in comparison with M0 and against variant lineages of B.1.617.2 (Delta, India), B.1.617.2.1 (Delta Plus, India), B.1.351 (Beta, SA) and B.1.1.7 (Alpha, UK) are elevated at M3, M6 and M12 in comparison with M0. However, NAb levels against B.1.1.529 (Omicron) was consistently below the limit of detection except at M12.Conclusion: Thus, Covaxin induces an enhanced humoral immune response, with persistence till at least 12 months post-vaccination against most SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background Multisystem inflammatory syndrome in children (MIS-C) is a rare manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children that can result in increased morbidity and mortality. The inflammatory underpinnings of MIS-C have not been examined in detail. Methods We examined the plasma levels of acute phase proteins and microbial translocation markers in children with MIS-C, children with acute coronavirus disease 2019 (COVID-19) infection, SARS-CoV-2-seropositive children, and controls. Results MIS-C children exhibited significantly higher levels of C-reactive protein (CRP), alpha2 macroglobulin (α2M), serum amyloid P (SAP), lipopolysaccharide (LPS), sCD14, and LPS binding protein (LBP) and significantly lower levels of haptoglobin (Hp) in comparison with seropositive, control, and/or COVID-19 children. In addition, COVID-19 children exhibited significantly higher levels of most of the above markers in comparison with seropositive and control children. Principal component analysis using a set of these markers could clearly discriminate MIS-C and COVID-19 from seropositive and control children. MIS-C children requiring pediatric intensive care unit admission and COVID-19 children with severe disease had higher levels of CRP, SAP, and/or sCD14 at admission. Conclusions Our study describes the role of systemic inflammation and microbial translocation markers in children with MIS-C and COVID-19 and therefore helps in advancing our understanding of the pathogenesis of different presentations of SARS-CoV-2 infection in children. [ABSTRACT FROM AUTHOR]

Background Preterm birth (PTB) rates are high in human immunodeficiency virus (HIV)–infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting that risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations, but its role in HIV-infected population have not been studied; in addition, the immune pathways involved are not clear and noninvasive immune markers with predictive value are lacking. Our objective was to determine the association of select markers of inflammation with PTB in HIV-1–infected pregnant women. Methods Within a randomized trial of pregnant women receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested a case-control study (n = 107; 26 cases, 81 controls) to determine the association of maternal inflammation with PTB. Cases were defined as PTB (<37 weeks’ gestational age). We assessed inflammation by measuring plasma levels of markers of general inflammation (C-reactive protein [CRP]), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]). Multivariable logistic regression was used to determine the odds of PTB per log2 increase of each marker. Results In multivariable models, there was increased odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24–4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43–10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18–4.41) but not log2 CRP (aOR, 0.72; 95% CI,.48–1.09). Conclusions Our results show that select immune markers can identify women at higher risk for PTB in HIV-1–infected populations and suggest that modulating gut barrier integrity and microbial translocation may affect PTB. Clinical Trials Registration NCT00061321. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (DM) is a risk factor for tuberculosis among individuals with latent Mycobacterium tuberculosis infection. To explore the influence of DM on CD8(+) T-cell responses during latent M. tuberculosis infection, we estimated the cytokine and cytotoxic marker expression pattern in individuals with latent M. tuberculosis infection with DM and those with latent M. tuberculosis infection without DM. Among individuals with latent M. tuberculosis infection, those with DM had diminished frequencies of CD8(+) T-helper type 1 (Th1), Th2, and Th17 cells following stimulation by M. tuberculosis antigen and enhanced frequencies of CD8(+) T cells expressing cytotoxic markers, compared with those without DM. Thus, our results suggest that coincident DM modulates CD8(+) T-cell function during latent M. tuberculosis infection. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus type 2 (DM) is known to be a major risk factor for the development of active tuberculosis, although its influence on latent Mycobacterium tuberculosis infection (hereafter, “latent infection”) remains poorly characterized.Methods. We examined circulating plasma cytokine levels in individuals with latent infection with DM or pre-DM (ie, intermediate hyperglycemia) and compared them to levels in patients with latent infection and normal glycemic control.Results. In persons with DM or pre-DM, latent infection is characterized by diminished circulating levels of type 1 (interferon γ, interleukin 2, and tumor necrosis factor α) and type 17 (interleukin 17F) cytokines. This was associated with decreased systemic levels of other proinflammatory cytokines (interleukin 1β and interleukin 18) and the antiinflammatory cytokine interleukin 10 but not with decreased systemic levels of type 2 cytokines. Moreover, latently infected individuals with DM had diminished levels of spontaneous and M. tuberculosis antigen–specific levels of type 1 and type 17 cytokines when antigen-stimulated whole blood was examined. Finally, there was no significant correlation between the levels of any of the cytokines measured (with the exception of interleukin 22) with hemoglobin A1c levels.Conclusions. Our data reveal that latent infection in the presence of DM or pre-DM, is characterized by diminished production of cytokines, implicated in the control of M. tuberculosis activation, allowing for a potential immunological mechanism that could account for the increased risk of active tuberculosis in latently infected individuals with DM. [ABSTRACT FROM AUTHOR]

Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined.Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM.Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β.Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. [ABSTRACT FROM PUBLISHER]

Background Type 1, type 17, and other proinflammatory cytokines are important in host immunity to tuberculosis (TB) in animal models. However, their role in human immunity to TB is not completely understood. Methods To examine the association of proinflammatory cytokines with pulmonary TB (PTB), we examined the plasma levels of type 1 (interferon [IFN]γ and tumor necrosis factor [TNF]α), type 17 (interleukin [IL]-17A and IL-17F), and other proinflammatory (IL-6, IL-12, and IL-1β) cytokines in individuals with PTB, latent TB (LTB), or healthy controls (HC). Results Individuals with PTB exhibited significantly higher plasma levels of most of the above cytokines compared with LTB or HC individuals. Principal component analysis based on these cytokines could clearly distinguish PTB from both LTB or HC individuals. Pulmonary TB individuals with bilateral or cavitary disease exhibited significantly higher levels of IFNγ, TNFα, IL-17A, and IL-1β compared with those with unilateral or noncavitary disease. Pulmonary TB individuals also exhibited a significant positive relationship between IFNγ, TNFα, and IL-17A levels and bacterial burdens. In addition, PTB individuals with delayed culture conversion exhibited significantly higher levels of IFNγ, TNFα, IL-17A, and IL-1β at baseline. Finally, the plasma levels of all the cytokines examined were significantly reduced after successful chemotherapy. Conclusions Therefore, our data demonstrate that PTB is associated with heightened levels of plasma proinflammatory cytokines, which are reversed after chemotherapy. Our data also reveal that proinflammatory cytokines are markers of disease severity, bacterial burden, and delayed culture conversion in PTB. [ABSTRACT FROM AUTHOR]