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1.
Int J Mol Sci ; 23(4)2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1760640

ABSTRACT

Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression.


Subject(s)
COVID-19/etiology , Tuberculosis/diagnosis , Tuberculosis/etiology , COVID-19/immunology , Coinfection , Host-Pathogen Interactions , Humans , Inflammation/microbiology , Inflammation/pathology , Inflammation/virology , Lymphopenia/microbiology , Lymphopenia/virology , Mycobacterium tuberculosis/pathogenicity , SARS-CoV-2/pathogenicity
2.
Int J Mol Sci ; 22(22)2021 Nov 21.
Article in English | MEDLINE | ID: covidwho-1534090

ABSTRACT

Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.


Subject(s)
Antitubercular Agents/chemistry , Mycobacterium tuberculosis/drug effects , Triterpenes/chemistry , Tuberculosis/drug therapy , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antitubercular Agents/pharmacology , DNA-Directed RNA Polymerases/antagonists & inhibitors , DNA-Directed RNA Polymerases/genetics , Drug Design , Drug Resistance, Bacterial/genetics , Humans , Molecular Docking Simulation , Molecular Structure , Mycobacterium tuberculosis/pathogenicity , Rifampin/pharmacology , Triterpenes/pharmacology , Tuberculosis/genetics , Tuberculosis/microbiology
4.
Viruses ; 13(5)2021 05 17.
Article in English | MEDLINE | ID: covidwho-1234832

ABSTRACT

By the middle of 2021, we are still immersed in the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The concurrence of this new pandemic in regions where human immunodeficiency virus (HIV) and tuberculosis (TB) infections possess the same epidemiological consideration, has arisen concerns about the prognosis, clinical management, symptomatology, and treatment of patients with triple infection. At the same time, healthcare services previously devoted to diagnosis and treatment of TB and HIV are being jeopardized by the urgent need of resources and attention for COVID-19 patients. The aim of this review was to collect any article considering the three conditions (HIV, TB, and SARS-CoV-2), included in PubMed/Medline and published in the English language since the beginning of the COVID-19 pandemic. We focused on detailed descriptions of the unusual cases describing the three co-infections. Eighty-four out of 184 publications retrieved met our inclusion criteria, but only three of them reported cases (five in total) with the three concomitant infections. The clinical evolution, management, and therapy of all of them were not different from mild/severe cases with exclusive COVID-19; the outcome was not worse either, with recovery for the five patients. Cases of patients with COVID-19 besides HIV and TB infections are scarce in literature, but studies deliberately embracing the triple infection as a priori inclusion criterion should be carried out in order to provide a complete understanding of joint influence.


Subject(s)
COVID-19/complications , Coinfection/epidemiology , COVID-19/epidemiology , Diagnostic Tests, Routine , HIV/pathogenicity , HIV Infections/complications , HIV Infections/epidemiology , Humans , Mycobacterium tuberculosis/pathogenicity , Pandemics , SARS-CoV-2/pathogenicity , Tuberculosis/complications , Tuberculosis/epidemiology
7.
PLoS Biol ; 18(12): e3000963, 2020 12.
Article in English | MEDLINE | ID: covidwho-1040033

ABSTRACT

Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.


Subject(s)
HIV Infections/complications , Latent Tuberculosis/complications , Latent Tuberculosis/diagnosis , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/etiology , AIDS-Related Opportunistic Infections/microbiology , Adult , CD4-Positive T-Lymphocytes , Cohort Studies , Disease Progression , Female , HIV Infections/metabolism , HIV-1/pathogenicity , Humans , Interferon-gamma , Latent Tuberculosis/metabolism , Male , Middle Aged , Mycobacterium tuberculosis/pathogenicity , Opportunistic Infections/complications , Risk , Tuberculosis/complications , Tuberculosis/diagnosis , Viral Load/immunology
8.
Tuberculosis (Edinb) ; 126: 102020, 2021 01.
Article in English | MEDLINE | ID: covidwho-926650

ABSTRACT

Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are currently the two main causes of death among infectious diseases. There is an increasing number of studies trying to elucidate the interactions between Mycobacterium tuberculosis and SARS-CoV-2. Some of the first case reports point to a worsening of respiratory symptoms in co-infected TB/COVID-19 individuals. However, data from the cohort studies has shown some conflicting results. This study proposes to conduct a systematic review on the current literature on TB/COVID-19 co-infection cohorts, evaluating clinical and epidemiological data, focusing on its implications to the immune system. From an immunological perspective, the TB/COVID-19 co-infection has the potential to converge in a "perfect storm". The disorders induced by each pathogen to the immunomodulation tend to induce an unbalanced inflammatory response, which can promote the progression and worsening of both diseases. Understanding the nature of the interactions between M. tuberculosis and SARS-CoV-2 will be crucial for the development of therapeutic strategies against co-infection.


Subject(s)
COVID-19/virology , Inflammation Mediators/immunology , Lung/microbiology , Mycobacterium tuberculosis/pathogenicity , SARS-CoV-2/pathogenicity , Tuberculosis, Pulmonary/microbiology , Animals , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Coinfection , Disease Progression , Host-Pathogen Interactions , Humans , Lung/immunology , Lung/virology , Mycobacterium tuberculosis/immunology , Prognosis , SARS-CoV-2/immunology , Signal Transduction , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/therapy
9.
Am J Trop Med Hyg ; 103(4): 1593-1596, 2020 10.
Article in English | MEDLINE | ID: covidwho-890582

ABSTRACT

Coinfection of SARS-CoV-2/Mycobacterium tuberculosis (MTB) in patients with HIV/AIDS has not been previously reported. Here, we present two cases of coinfection of SARS-CoV-2 and MTB in patients with HIV. The first case is a 39-year-old patient who was admitted with a 7-day history of fever, myalgia, headache, and cough. The second patient is a 43-year-old man who had a 1-month history of cough with hemoptoic sputum, evolving to mild respiratory distress in the last 7 days. Both patients already had pulmonary tuberculosis and subsequently developed SARS-CoV-2 infection during the 2020 pandemic. Nonadherence to antiretroviral treatment may have been a factor in the clinical worsening of the patients.


Subject(s)
Coronavirus Infections/microbiology , Cough/microbiology , HIV Infections/microbiology , Patient Compliance/psychology , Pneumonia, Viral/microbiology , Respiratory Distress Syndrome/microbiology , Tuberculosis, Pulmonary/microbiology , Adult , Anti-HIV Agents/therapeutic use , Betacoronavirus/pathogenicity , COVID-19 , Coinfection , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cough/drug therapy , Cough/immunology , Cough/virology , HIV/pathogenicity , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Humans , Male , Mycobacterium tuberculosis/pathogenicity , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/virology , SARS-CoV-2 , Tomography, X-Ray Computed , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/virology
11.
Am J Trop Med Hyg ; 103(4): 1597-1599, 2020 10.
Article in English | MEDLINE | ID: covidwho-725412

ABSTRACT

COVID-19, designated as SARS-CoV-2, has caused millions of infections worldwide, including in patients with concomitant infections. Here, we report two unusual cases of patients with triple infections of SARS-CoV-2, Mycobacterium tuberculosis, and HIV. Both cases were confirmed through microbiological and immunological studies. The acute respiratory phase in both patients was treated with supplemental oxygen. Antituberculosis and antiretroviral therapies were started simultaneously. In 2 weeks, both patients demonstrated clinical improvement and recovery from COVID-19. Our findings suggest that even in cases of triple infection, clinical management together with respiratory therapy contributes to patient survival.


Subject(s)
Antitubercular Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/therapy , HIV Infections/therapy , Heparin/therapeutic use , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/therapy , Tuberculosis, Pulmonary/therapy , Adult , Betacoronavirus/pathogenicity , COVID-19 , Coinfection , Convalescence , Coronavirus Infections/immunology , Coronavirus Infections/microbiology , Coronavirus Infections/virology , HIV/pathogenicity , HIV Infections/immunology , HIV Infections/microbiology , HIV Infections/virology , Humans , Male , Middle Aged , Mycobacterium tuberculosis/pathogenicity , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/microbiology , Pneumonia, Viral/virology , Positive-Pressure Respiration/methods , SARS-CoV-2 , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/virology
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