Early Experience of High-dose Intravenous Mycobacterium w in Critically Ill Patients of COVID-19

Patel, Parth; Patel, Sudhendu; Shah, Vidhi; Aswani, Varsha; Narwaria, Mahendra

doi:10.5005/jp-journals-10071-23963

Cited by 4 publications

(1 citation statement)

References 14 publications

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“…Immunization with M. vaccae NCTC 11659 via the subcutaneous route can, (1) by itself, decrease hippocampal Nfkbia and Nlrp3 mRNA expression and (2) prevent stress-induced microglial priming, as assessed by LPS-induced increases in Il1b and Nfkbia mRNA expression in freshly isolated hippocampal microglia [ 12 , 13 , 14 , 15 ]. However, the direct effects of M. vaccae NCTC 11659 on microglia, as might occur following the translocation of the live bacillus across the blood–cerebrospinal fluid barrier, for example, after the intravenous administration of a heat-killed suspension of Mycobacterium , as recently conducted using Mycobacterium indicus pranii ( Mycobacterium w ) in critically ill COVID-19 patients [ 16 , 17 ] or as recently conducted using the intravenous administration of the Bacillus Calmette–Guérin (BCG) vaccine in macaques [ 18 ], have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Effects of Mycobacterium vaccae NCTC 11659 and Lipopolysaccharide Challenge on Polarization of Murine BV-2 Microglial Cells

Desmond,

Holbrook,

Wright

et al. 2023

IJMS

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Previous studies have shown that the in vivo administration of soil-derived bacteria with anti-inflammatory and immunoregulatory properties, such as Mycobacterium vaccae NCTC 11659, can prevent a stress-induced shift toward an inflammatory M1 microglial immunophenotype and microglial priming in the central nervous system (CNS). It remains unclear whether M. vaccae NCTC 11659 can act directly on microglia to mediate these effects. This study was designed to determine the effects of M. vaccae NCTC 11659 on the polarization of naïve BV-2 cells, a murine microglial cell line, and BV-2 cells subsequently challenged with lipopolysaccharide (LPS). Briefly, murine BV-2 cells were exposed to 100 µg/mL whole-cell, heat-killed M. vaccae NCTC 11659 or sterile borate-buffered saline (BBS) vehicle, followed, 24 h later, by exposure to 0.250 µg/mL LPS (Escherichia coli 0111: B4; n = 3) in cell culture media vehicle (CMV) or a CMV control condition. Twenty-four hours after the LPS or CMV challenge, cells were harvested to isolate total RNA. An analysis using the NanoString platform revealed that, by itself, M. vaccae NCTC 11659 had an “adjuvant-like” effect, while exposure to LPS increased the expression of mRNAs encoding proinflammatory cytokines, chemokine ligands, the C3 component of complement, and components of inflammasome signaling such as Nlrp3. Among LPS-challenged cells, M. vaccae NCTC 11659 had limited effects on differential gene expression using a threshold of 1.5-fold change. A subset of genes was assessed using real-time reverse transcription polymerase chain reaction (real-time RT-PCR), including Arg1, Ccl2, Il1b, Il6, Nlrp3, and Tnf. Based on the analysis using real-time RT-PCR, M. vaccae NCTC 11659 by itself again induced “adjuvant-like” effects, increasing the expression of Il1b, Il6, and Tnf while decreasing the expression of Arg1. LPS by itself increased the expression of Ccl2, Il1b, Il6, Nlrp3, and Tnf while decreasing the expression of Arg1. Among LPS-challenged cells, M. vaccae NCTC 11659 enhanced LPS-induced increases in the expression of Nlrp3 and Tnf, consistent with microglial priming. In contrast, among LPS-challenged cells, although M. vaccae NCTC 11659 did not fully prevent the effects of LPS relative to vehicle-treated control conditions, it increased Arg1 mRNA expression, suggesting that M. vaccae NCTC 11659 induces an atypical microglial phenotype. Thus, M. vaccae NCTC 11659 acutely (within 48 h) induced immune-activating and microglial-priming effects when applied directly to murine BV-2 microglial cells, in contrast to its long-term anti-inflammatory and immunoregulatory effects observed on the CNS when whole-cell, heat-killed preparations of M. vaccae NCTC 11659 were given peripherally in vivo.

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Section: Introductionmentioning

confidence: 99%

Effects of Mycobacterium vaccae NCTC 11659 and Lipopolysaccharide Challenge on Polarization of Murine BV-2 Microglial Cells

Desmond,

Holbrook,

Wright

et al. 2023

IJMS

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Genome wide screening to discover novel toxin–antitoxin modules in Mycobacterium indicus pranii; perspective on gene acquisition during mycobacterial evolution

Bahl,

Rakshit,

Pandey

et al. 2024

Biotech and App Biochem

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Mycobacterium indicus pranii (MIP), a benign saprophyte with potent immunomodulatory attributes, holds a pivotal position in mycobacterial evolution, potentially serving as the precursor to the pathogenic Mycobacterium avium complex (MAC). Despite its established immunotherapeutic efficacy against leprosy and notable outcomes in gram‐negative sepsis and COVID‐19 cases, the genomic and biochemical features of MIP remain largely elusive. This study explores the uncharted territory of toxin‐antitoxin (TA) systems within MIP, hypothesizing their role in mycobacterial pathogenicity regulation. Genome‐wide screening, employing diverse databases, unveils putative TA modules in MIP, setting the stage for a comparative analysis with known modules in Mycobacterium tuberculosis, Mycobacterium smegmatis, Escherichia coli, and Vibrio cholerae. The study further delves into the TA network of MAC and Mycobacterium intracellulare, unraveling interactive properties and family characteristics of identified TA modules in MIP. This comprehensive exploration seeks to illuminate the contribution of TA modules in regulating virulence, habitat diversification, and the evolutionary pathogenicity of mycobacteria. The insights garnered from this investigation not only enhance our understanding of MIP's potential as a vaccine candidate but also hold promise in optimizing tuberculosis drug regimens for expedited recovery.

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Incidence and outcomes of splanchnic vein thrombosis after diagnosis of COVID-19 or COVID-19 vaccination: a systematic review and meta-analysis

Zheng

Gao

Wang

et al. 2022

J Thromb Thrombolysis

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Coronavirus disease 2019 (COVID-19) and COVID-19 vaccination may cause splanchnic vein thrombosis (SVT), which is potentially fatal. The present study aims to pool the incidence and outcomes of SVT patients with COVID-19 or having received COVID-19 vaccines. The PubMed, EMBASE, and Cochrane databases were searched. Based on the data from cohort studies, meta-analyses were performed to evaluate the incidence of SVT in COVID-19 patients or people having received COVID-19 vaccines. Pooled proportions were calculated. Based on the individual data from case reports, logistic regression analyses were performed to identify factors associated with death in SVT patients. Odds ratios (ORs) were calculated. Among 654 papers initially identified, 135 were included. Based on 12 cohort studies, the pooled incidence of SVT in COVID-19 patients was 0.6%. Data were insufficient to estimate the incidence of SVT after COVID-19 vaccination. Based on 123 case reports, the mortality was 14% (9/64) in SVT patients with COVID-19 and 25% (15/59) in those who received COVID-19 vaccines. Univariate analyses demonstrated that age (OR = 1.061; p = 0.017), diabetes mellitus (OR = 14.00; p = 0.002), anticoagulation (OR = 0.098; p = 0.004), and bowel resection (OR = 16.00; p = 0.001) were significantly associated with death in SVT patients with COVID-19; and anticoagulation (OR = 0.025; p = 0.003) and intravenous immunoglobulin (OR = 0.175; p = 0.046) were significantly associated with death in SVT patients who received COVID-19 vaccines. Multivariate analyses did not identify any independent factor for death in both patients. SVT in COVID-19 patients and in subjects who received COVID-19 vaccines carries a high mortality, but may be improved by anticoagulation. PROSPERO Identifier CRD42022315254. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11239-022-02732-3.

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Early Experience of High-dose Intravenous Mycobacterium w in Critically Ill Patients of COVID-19

Cited by 4 publications

References 14 publications

Effects of Mycobacterium vaccae NCTC 11659 and Lipopolysaccharide Challenge on Polarization of Murine BV-2 Microglial Cells

Effects of Mycobacterium vaccae NCTC 11659 and Lipopolysaccharide Challenge on Polarization of Murine BV-2 Microglial Cells

Genome wide screening to discover novel toxin–antitoxin modules in Mycobacterium indicus pranii; perspective on gene acquisition during mycobacterial evolution

Incidence and outcomes of splanchnic vein thrombosis after diagnosis of COVID-19 or COVID-19 vaccination: a systematic review and meta-analysis

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