Editorial: Pathogenesis, diagnostics, treatments of Mycobacterium tuberculosis and its co-infection with HIV or SARS-CoV-2.
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ABSTRACT:
SUBMITTER: Sharma D
PROVIDER: S-EPMC10830670 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
Publications
Editorial: Pathogenesis, diagnostics, treatments of <i>Mycobacterium tuberculosis</i> and its co-infection with HIV or SARS-CoV-2.
Frontiers in cellular and infection microbiology 20240118
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Project description:The respiratory disease caused by the Coronavirus infectious disease 2019 (COVID19) has spread rapidly since December 2019 in Wuhan, China. This new strain of Coronavirus is similar to the SARS Corona virus and has been termed SARS-CoV-2. Both viruses have emerged from bats and adapted to humans. On March 11, 2020 COVID19 was declared Pandemic by the WHO and as of May 1, 2020 COVID19 disease continues to grow rapidly with 3,400,595 cases and 239,583 deaths world-wide. This review describes the biology of SARSCOV2, Detection, Macrophage-Mediated Pathogenesis and Potential Treatments.
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Project description:BackgroundSARS-CoV-2 infections usually cause immune dysregulation in the human body. Studies of immunological changes resulting from coinfections with Mycobacterium tuberculosis (Mtb) or HIV are limited.MethodsWe conducted a retrospective study focusing on patients with COVID-19. A total of 550 patients infected with SARS-CoV-2 were enrolled in our study and categorized into four groups based on the presence of coinfections; 166 Delta-infected patients, among whom 103 patients had no coinfections, 52 who were coinfected with Mtb, 11 who were coinfected with HIV, and 384 Omicron-infected patients. By collecting data on epidemiologic information, laboratory findings, treatments, and clinical outcomes, we analyzed and compared clinical and immunological characteristics.ResultsCompared with those in the Delta group, the median white blood cell, CD4 + T-cell and B-cell counts were lower in the Mtb group and the HIV group. Except for those in the Omicron group, more than half of the patients in the three groups had abnormal chest CT findings. Among the three groups, there were no significant differences in any of the cytokines. Compared with those in the Delta group, the disease duration and LOS were longer in the Mtb group and the HIV group. For unvaccinated Delta-infected patients, in the Mtb and HIV groups, the number of B cells and CD4 + T cells was lower than that in the Delta group, with no significant difference in the LOS or disease duration. In the Mtb group, three (6%) patients presented with a disease duration greater than four months and had decreased lymphocyte and IL17A counts, possibly due to double infections in the lungs caused by SARS-CoV-2 and M. tuberculosis.ConclusionsWe found that SARS-CoV-2 patients coinfected with Mtb or HIV exhibited a longer disease duration and longer LOS, with a decrease in B cells and CD4 + T cells, suggesting that these cells are related to immune function. Changes in cytokine levels suggest that coinfection with Mtb or HIV does not result in dysregulation of the immune response. Importantly, we discovered a chronic course of coinfection involving more than four months of Mtb and SARS-CoV-2 infection.
| S-EPMC10882883 | biostudies-literature
Project description:(1) Background: Many co-infections of Mycobacterium tuberculosis (MTB) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have emerged since the occurrence of the SARS-CoV-2 pandemic. This study aims to design an effective preventive multi-epitope vaccine against the co-infection of MTB and SARS-CoV-2. (2) Methods: The three selected proteins (spike protein, diacylglycerol acyltransferase, and low molecular weight T-cell antigen TB8.4) were predicted using bioinformatics, and 16 epitopes with the highest ranks (10 helper T lymphocyte epitopes, 2 CD8+ T lymphocytes epitopes, and 4 B-cell epitopes) were selected and assembled into the candidate vaccine referred to as S7D5L4. The toxicity, sensitization, stability, solubility, antigenicity, and immunogenicity of the S7D5L4 vaccine were evaluated using bioinformatics tools. Subsequently, toll-like receptor 4 docking simulation and discontinuous B-cell epitope prediction were performed. Immune simulation and codon optimization were carried out using immunoinformatics and molecular biology tools. (3) Results: The S7D5L4 vaccine showed good physical properties, such as solubility, stability, non-sensitization, and non-toxicity. This vaccine had excellent antigenicity and immunogenicity and could successfully simulate immune responses in silico. Furthermore, the normal mode analysis of the S7D5L4 vaccine and toll-like receptor 4 docking simulation demonstrated that the vaccine had docking potential and a stable reaction. (4) Conclusions: The S7D5L4 vaccine designed to fight against the co-infection of MTB and SARS-CoV-2 may be safe and effective. The protective efficacy of this promising vaccine should be further verified using in vitro and in vivo experiments.
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Project description:On 4th November 2021, the first oral antiviral drug for COVID-19, molnupiravir (Lagevrio®), received full regulatory approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK. Molnupiravir is an orally bioavailable antiviral drug for use at home when a SARS-CoV-2 test is positive. On 22nd December 2022, the FDA granted emergency use authorization (EUA) for the oral antiviral drug, nirmatrelvir/ritonavir (Paxlovid®) for adults and children with mild and moderate COVID-19 at increased risk of progression to severe COVID-19. These regulatory drug approvals come at a crucial time when new variants of concern of the SARS-CoV-2 virus are spreading rapidly. Although the FDA approved remdesivir (Veklury®) on 22nd October 2020 for use in adults and children for the treatment of COVID-19 requiring hospitalization, its use has been limited by the requirement for intravenous administration in a healthcare facility. The four FDA-approved therapeutic neutralizing monoclonal antibodies, imdevimab, bamlanivimab, etesevimab, and casirivimab are costly and also require medically-supervised intravenous administration. The availability of effective, low-cost oral antiviral drugs available in a community setting that can be used at an early stage of SARS-CoV-2 infection is now a priority in controlling COVID-19. An increasing number of repurposed antiviral drugs are currently under investigation or in the early stages of regulatory approval. This Editorial aims to present an update on the current status of orally bioavailable antiviral drug treatments for SARS-CoV-2 infection.
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Project description:For three years, the novel coronavirus disease 2019 (COVID-19) pandemic, caused by infection of the SARS-CoV-2 virus, has completely changed our lifestyles and prepared us to live with this novel pneumonia for years to come. Given that pre-existing flu is caused by the influenza A virus, we have begun unprecedently co-coping with two different respiratory diseases at the same time. Hence, we draw a comparison between SARS-CoV-2 and influenza A virus based on the general characteristics, especially the main variants' history and the distribution of the two viruses. SARS-CoV-2 appeared to mutate more frequently and independently of locations than the influenza A virus. Furthermore, we reviewed present clinical trials on combined management against COVID-19 and influenza in order to explore better solutions against both at the same time.
| S-EPMC10051779 | biostudies-literature
Project description:SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) are major infectious causes of death, with meta-analyses and population-based studies finding increased mortality in co-infected patients simultaneously diagnosed with COVID-19 and tuberculosis (TB). There is a need to understand the immune interaction between SARS-CoV-2 and Mtb which impacts poor outcomes for those co-infected. We performed a PubMed and preprint search using keywords [SARS-CoV-2] AND [tuberculosis] AND [Immune response], including publications after January 2020, excluding reviews or opinions. Abstracts were evaluated by authors for inclusion of data specifically investigating the innate and/or acquired immune responses to SARS-CoV-2 and Mtb in humans and animal models, immunopathological responses in co-infection and both trials and investigations of potential protection against SARS-CoV-2 by Bacille Calmette Guérin (BCG). Of the 248 articles identified, 39 were included. Incidence of co-infection is discussed, considering in areas with a high burden of TB, where reported co-infection is likely underestimated. We evaluated evidence of the clinical association between COVID-19 and TB, discuss differences and similarities in immune responses in humans and in murine studies, and the implications of co-infection. SARS-CoV-2 and Mtb have both been shown to modulate immune responses, particularly of monocytes, macrophages, neutrophils, and T cells. Co-infection may result in impaired immunity to SARS-CoV-2, with an exacerbated inflammatory response, while T cell responses to Mtb may be modulated by SARS-CoV-2. Furthermore, there has been no proven potential COVID-19 clinical benefit of BCG despite numerous large-scale clinical trials.
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Project description:BackgroundTuberculosis (TB) is still one of the most important causes of death worldwide. The lack of timely attention on TB diagnosis and treatment during the coronavirus disease 2019 (COVID-19) pandemic is a potential threat to health issues and may have severe consequences for patients and health systems. There is not much information on the management of TB during this period. Here, we reviewed the current literature to evaluate the rate of Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 coinfections and interactions between these infectious agents.MethodsSeveral databases, including Web of Science, Scopus, and MEDLINE (via PubMed), were searched for original articles addressing TB and COVID-19 diseases published from December 2019 to April 2021.ResultsOf 3,879 articles, 57 articles were included in this study, and among 106,033 patients affected by COVID-19, 891 also had TB. Overall, investigators found a consistent increase in C-reactive protein, D-dimer (especially in patients with severe clinical manifestation), erythrocyte sedimentation rate, lactate dehydrogenase, alanine aminotransferase, and a reduction of lymphocytes. The respiratory symptoms of TB/COVID-19 patients were similar to those of TB patients, but the risk of developing pulmonary TB increased in COVID-19 patients. Also, the mortality rate in TB/COVID-19 patients was higher than that in patients affected only by COVID-19 or TB.ConclusionSome reports indicated worsening respiratory symptoms and even activation of latent TB after COVID-19 or vice versa. It seems that both active and previously treated TB constituted a risk factor for COVID-19 in terms of severity and mortality, regardless of other underlying diseases and patient status. Health systems should not neglect TB during this era of the ongoing COVID-19 pandemic by setting up appropriate diagnostic and clinical management algorithms.
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Project description:IntroductionTo ensure there is adequate investment into diagnostics, an understanding of the magnitude of impact and return on investment is necessary. We, therefore, sought to understand the health and economic impacts of the molecular diagnostic programme in South Africa, to deepen the understanding of the broad value of diagnostics and guide future healthcare investments.MethodsWe calculated the 10-year (where data were available) total cost and disability-adjusted life-years (DALYs) averted associated with molecular testing for tuberculosis diagnosis (2013-2022), HIV viral load monitoring (2013-2022), early infant diagnosis of HIV infection (2013-2022) and SARS-CoV-2 testing (2020-2022), based on the actual number of molecular tests conducted in South Africa for the respective time periods. We then calculated the economic value associated with those health gains and subsequent return on investment.ResultsSince the inception of the molecular diagnostics programme in South Africa, approximately 4.3 million DALYs (uncertainty range (UR): 2.8-5.8 million) have been averted as a direct consequence of this programme. This has generated an estimated US$28.3 billion in economic value due to these health gains (UR$18.4-UR$38.7 billion). The return on investment varied by specific diagnostic test (20.3 (UR 15.2-25.4) for tuberculosis, 7.7 (UR 1.6-13.9) for HIV viral load testing, 63.0 (UR 63.0-65.5) for early infant diagnosis of HIV and 2.5 (UR 0.7-4.6) for SARS-CoV-2), for an average of 13.9 (UR 9.0-18.9) for the entire molecular diagnostics programme or US$13.9 of value for each UR$1 invested.ConclusionsThe molecular diagnostics programme in South Africa generated a significant amount of health gains and economic value associated with these health gains. The return on investment rivals other high-impact public health interventions such as childhood vaccination. The molecular diagnostics programme in South Africa is highly impactful and will continue to be an excellent investment in South African public health expenditure.
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Project description:Tuberculosis (TB) remains a significant public health concern in the 21st century, especially due to drug resistance, coinfection with diseases like immunodeficiency syndrome (AIDS) and coronavirus disease 2019, and the lengthy and costly treatment protocols. In this review, we summarize the pathogenesis of TB infection, therapeutic targets, and corresponding modulators, including first-line medications, current clinical trial drugs and molecules in preclinical assessment. Understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection and important biological targets can lead to innovative treatments. While most antitubercular agents target pathogen-related processes, host-directed therapy (HDT) modalities addressing immune defense, survival mechanisms, and immunopathology also hold promise. Mtb's adaptation to the human host involves manipulating host cellular mechanisms, and HDT aims to disrupt this manipulation to enhance treatment effectiveness. Our review provides valuable insights for future anti-TB drug development efforts.
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