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1.
BMJ Open Respir Res ; 9(1)2022 06.
Article in English | MEDLINE | ID: covidwho-1909782

ABSTRACT

INTRODUCTION: We evaluated the yield of tuberculosis (TB) contact investigation in Brunei Darussalam, and identified the associated factors for latent TB infection (LTBI) diagnosis, as well as for initiating and completing LTBI treatment. METHODS: Data were extracted and digitalised for all close contacts of pulmonary TB (PTB) cases at the National TB Coordinating Centre from January 2009 to December 2018. Generalising estimating equations logistic regression models were used to determine the associated factors. Manual matching against electronic health records system was done to identify contacts who had progressed to active TB disease. RESULTS: Among 10 537 contacts, 9.9% (n=1047) were diagnosed as LTBI, out of which 43.0% (n=450) initiated LTBI treatment. Among those who initiated, 74.0% (n=333) completed LTBI treatment. Contact factors associated with LTBI diagnosis include being male (adjusted OR (aOR)=1.18 (95% CI 1.03 to 1.34)), local (aOR=0.70 (95% CI 0.56 to 0.88)) and a household contact (aOR=1.59 (95% CI 1.26 to 1.99)). Contacts of index cases who were <60 years old and diagnosed as smear positive PTB (aOR=1.62 (95% CI 1.19 to 2.20)) had higher odds of being diagnosed with LTBI. Local LTBI cases had higher odds of initiating LTBI treatment (aOR=1.86 (95% CI 1.26 to 2.73)). Also, LTBI cases detected from local (aOR=2.32 (95% CI 1.08 to 4.97)) and smear positive PTB index cases (aOR=2.23 (95% CI 1.09 to 4.55)) had higher odds of completing LTBI treatment. Among 1047 LTBI cases, 5 (0.5%) had progressed to active PTB within 1-8 years post-LTBI diagnosis. DISCUSSION: LTBI burden is disproportionately high towards foreign nationals, with higher odds of LTBI diagnosis but lower odds of treatment initiation. Determining the reasons of not initiating LTBI treatment will be useful to help improve LTBI treatment uptake. Establishing digital databases and building TB laboratory capacity for molecular typing would be useful to determine the contribution of LTBI or reactivation towards TB incidence in Brunei.


Subject(s)
Latent Tuberculosis , Tuberculosis , Brunei/epidemiology , Contact Tracing , Factor Analysis, Statistical , Female , Humans , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Latent Tuberculosis/epidemiology , Male , Middle Aged , Tuberculosis/epidemiology
2.
Sci Rep ; 12(1): 9472, 2022 06 08.
Article in English | MEDLINE | ID: covidwho-1890261

ABSTRACT

Since COVID-19 outbreak, scientists have been interested to know whether there is any impact of the Bacillus Calmette-Guerin (BCG) vaccine against COVID-19 mortality or not. It becomes more relevant as a large population in the world may have latent tuberculosis infection (LTBI), for which a person may not have active tuberculosis but persistent immune responses stimulated by Mycobacterium tuberculosis antigens, and that means, both LTBI and BCG generate immunity against COVID-19. In order to understand the relationship between LTBI and COVID-19 mortality, this article proposes a measure of goodness of fit, viz., Goodness of Instrumental Variable Estimates (GIVE) statistic, of a model obtained by Instrumental Variables estimation. The GIVE statistic helps in finding the appropriate choice of instruments, which provides a better fitted model. In the course of study, the large sample properties of the GIVE statistic are investigated. As indicated before, the COVID-19 data is analysed using the GIVE statistic, and moreover, simulation studies are also conducted to show the usefulness of the GIVE statistic along with analysis of well-known Card data.


Subject(s)
COVID-19 , Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis , BCG Vaccine , COVID-19/epidemiology , COVID-19 Vaccines , Humans , Latent Tuberculosis/epidemiology
3.
BMJ Case Rep ; 15(5)2022 May 11.
Article in English | MEDLINE | ID: covidwho-1840566

ABSTRACT

Though the COVID-19 pandemic has made international headlines since 2020, behind the scenes, tuberculosis (TB) has remained a leading cause of global mortality. According to the WHO, TB is 1 of the top 10 causes of death globally, with about one-quarter of the world's population infected. This case report highlights a female patient who presented to the emergency department with signs and symptoms of COVID-19 and was admitted to hospital. When the patient demonstrated minimal clinical improvement after initiating treatment for COVID-19, further investigations uncovered concomitant reactivated TB. This case is helpful in underscoring the potential implications of the COVID-19 pandemic and current treatment guidelines on the global burden of TB, which could subsequently impact how practitioners approach screening and management of latent TB infection.


Subject(s)
COVID-19 , Latent Tuberculosis , Tuberculosis , Adrenal Cortex Hormones/therapeutic use , Female , Humans , Latent Tuberculosis/complications , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Pandemics , Tuberculosis/diagnosis
4.
Front Immunol ; 13: 856906, 2022.
Article in English | MEDLINE | ID: covidwho-1834405

ABSTRACT

Tuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent, second only to COVID-19 in 2020. TB is caused by infection with Mycobacterium tuberculosis (Mtb), that results either in a latent or active form of disease, the latter associated with Mtb spread. In the absence of an effective vaccine, epidemiologic modeling suggests that aggressive treatment of individuals with active TB (ATB) may curb spread. Yet, clinical discrimination between latent (LTB) and ATB remains a challenge. While antibodies are widely used to diagnose many infections, the utility of antibody-based tests to diagnose ATB has only regained significant traction recently. Specifically, recent interest in the humoral immune response to TB has pointed to potential differences in both targeted antigens and antibody features that can discriminate latent and active TB. Here we aimed to integrate these observations and broadly profile the humoral immune response across individuals with LTB or ATB, with and without HIV co-infection, to define the most discriminatory humoral properties and diagnose TB disease more easily. Using 209 Mtb antigens, striking differences in antigen-recognition were observed across latently and actively infected individuals that was modulated by HIV serostatus. However, ATB and LTB could be discriminated, irrespective of HIV-status, based on a combination of both antibody levels and Fc receptor-binding characteristics targeting both well characterized (like lipoarabinomannan, 38 kDa or antigen 85) but also novel Mtb antigens (including Rv1792, Rv1528, Rv2435C or Rv1508). These data reveal new Mtb-specific immunologic markers that can improve the classification of ATB versus LTB.


Subject(s)
COVID-19 , HIV Infections , Latent Tuberculosis , Tuberculosis , Antibodies , HIV Infections/complications , Humans
5.
J Infect Public Health ; 15(4): 400-405, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1828916

ABSTRACT

BACKGROUND: Healthcare workers are considered to be at a higher risk of acquiring tuberculosis (TB) infection than the general population. Clinical medical students are part of the healthcare team and clinical practice are done during their clinical rotation. They could be exposed to similar occupational risks as the healthcare workers. Most students who become infected have latent tuberculosis infection (LTBI) and may not exhibit any clinical symptoms. Some students with LTBI can progress to TB disease during clinical rotations in the hospitals. Therefore, screening for LTBI in this population represents hospital aspect of public health strategy and infection control in medical school in high TB burden countries. OBJECTIVE: We aimed to determine the prevalence of LTBI among fourth-year medical students and sixth-year medical students by using QuantiFERON-TB Gold Plus (QFT-Plus) and Tuberculin Skin Test (TST). METHODS: A cross-sectional study of fourth-year medical students (n = 73) and sixth-year medical students (n = 85) was conducted at the School of Medicine, Chulalongkorn University, Bangkok, Thailand. The medical students (n = 158) who met the eligibility criteria were recruited into the study. LTBI was detected by using QFT-Plus and some of the participants had a tuberculin skin test (TST). The TST was interpreted after 48-72 h. The participants who tested positive by QFT-Plus were considered to have LTBI. Demographic information and data on occupational TB exposure were collected via a questionnaire. A multivariate logistic regression was used to test for associations between independent variables and results of the QFT-Plus. RESULTS: A total of 158 participants were included in this study. The overall prevalence of LTBI was 6.3% (n = 10) as determined by QFT-Plus. The LTBI prevalence was higher in the sixth-year medical students (9.4%) compared to the fourth-year medical students (2.7%). Higher risk of LTBI was associated with sixth-year medical students (odds ratio, 3.69 [95%CI, 0.75-17.96]), but this was not significant. Moreover, history of occupational TB exposure without PPE yielded an odds ratio of 2.98 [95%CI, 0.68-13.12] but it was not statistically significant due to the small sample size. One hundred thirty-nine (88%) participants were BCG vaccinated as per the national vaccination requirements. No abnormal chest X-rays were found for any of the positive participants. Of the 158 participants, 41 (25.9%) of them had TST. Of the 41 participants, 6 (14.6%) tested positive at a cut-off of ≥ 10 mm for TST, which was concordant with QFT-Plus results. The agreement between the two tests was 0.57 using kappa coefficients. CONCLUSION: The screening of TB infection in new healthcare workers (HCWs), especially medical students, is essential to reduce future nosocomial TB incidences in the hospitals. This study showed that there was a high prevalence of LTBI among sixth-year medical students compared to fourth-year medical students. Our results suggest that tendency of higher LTBI prevalence might be associated with advanced clinical years, thus tailored public health education strategy and infection control in tertiary care hospitals for new healthcare workers in TB endemic countries may prevent nosocomial TB disease from developing in the future. Therefore, active surveillance should be done for all new HCWs, and TB preventive therapy should be administered to recent converters.


Subject(s)
Cross Infection , Latent Tuberculosis , Students, Medical , Cross-Sectional Studies , Hospitals, Teaching , Humans , Interferon-gamma Release Tests , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Prevalence , Thailand/epidemiology , Tuberculin Test
7.
J Infect Dis ; 225(8): 1317-1320, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1795259

ABSTRACT

We assessed the COVID-19 pandemic's impact on treatment of latent tuberculosis, and of active tuberculosis, at 3 centers in Montreal and Toronto, using data from 10 833 patients (8685 with latent tuberculosis infection, 2148 with active tuberculosis). Observation periods prior to declarations of COVID-19 public health emergencies ranged from 219 to 744 weeks, and after declarations, from 28 to 33 weeks. In the latter period, reductions in latent tuberculosis infection treatment initiation rates ranged from 30% to 66%. At 2 centers, active tuberculosis treatment rates fell by 16% and 29%. In Canada, cornerstone measures for tuberculosis elimination weakened during the COVID-19 pandemic.


Subject(s)
COVID-19 , Latent Tuberculosis , Tuberculosis , Canada/epidemiology , Humans , Pandemics/prevention & control , SARS-CoV-2 , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis/prevention & control
8.
Tuberculosis (Edinb) ; 134: 102186, 2022 05.
Article in English | MEDLINE | ID: covidwho-1783793

ABSTRACT

COVID-19 has affected the progress made in the prevention and treatment of tuberculosis (TB); hence, the mortality of tuberculosis has risen. Different strategies-based novel TB vaccine candidates have been developed. This study identifies strategies to overcome the limitations of Bacille Calmette-Guérin (BCG) in preventing latent infection and reactivation of TB. The latency antigen Rv0572c was selected based on the mechanism of interaction between Mycobacterium tuberculosis and its host. The rRv0572c protein was used to stimulate whole blood samples derived from patients with clinically diagnosed active TB (ATBs) or latent TB infections (LTBIs) and healthy control (HCs) donors, confirming that this protein can be recognized by T cells in patients with TB, especially LTBIs. C57BL/6 mice were used to investigate the immunogenicity of the rRv0572c protein emulsified in the liposome adjuvant dimethyldioctadecylammonium [DDA], monophosphoryl lipid A [MPLA], trehalose-6, 6'-dibehenate [TDB] (DMT). The results demonstrated that rRv0572c/DMT could boost BCG-primed mice to induce antigen-specific CD4+ T cell production and generate functional T cells dominated by antigen-specific CD8+ T cells. The rRv0572c/DMT vaccine could also trigger limited Th2 humoral immune responses. These findings suggest that rRv0572c/DMT is a potential subunit vaccine candidate that can be used as a booster vaccine for BCG.


Subject(s)
COVID-19 , Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis Vaccines , Tuberculosis , Adjuvants, Immunologic , Animals , Antigens, Bacterial , BCG Vaccine , CD8-Positive T-Lymphocytes , Humans , Liposomes , Mice , Mice, Inbred C57BL , Tuberculosis/prevention & control , Vaccines, Subunit
9.
Int J Environ Res Public Health ; 19(7)2022 04 05.
Article in English | MEDLINE | ID: covidwho-1776235

ABSTRACT

A significant drop in tuberculosis (TB) case-finding has been widely reported during the period of the COVID-19 pandemic. To address a decrease in TB notification, Belarus introduced laboratory TB testing in patients with the laboratory-confirmed coronavirus disease 2019 (COVID-19). We conducted a secondary analysis of health records among 844 patients with laboratory-confirmed COVID-19 diagnosis who were admitted to repurposed departments at TB hospitals and who were tested by Xpert MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) in five Belarus regions between April and October 2021. Quantitative analysis followed by 13 individual interviews with health managers, physicians, and nurses participating in the intervention. Most patients were male (64%) and mean age was 43.5 ± 16 years. One in twenty (n = 47, 5.6%) patients were co-infected with active pulmonary TB, and over one-third of them (n = 18) had rifampicin resistance. In-hospital mortality was comparable in patients with and without TB co-infection (2.1% and 2.3% respectively, p > 0.99). Laboratory TB testing among patients with COVID-19 at repurposed departments of TB hospitals is feasible in Belarus and may improve TB case-finding.


Subject(s)
Antibiotics, Antitubercular , COVID-19 , Coinfection , Latent Tuberculosis , Mycobacterium tuberculosis , Tuberculosis , Adult , Antibiotics, Antitubercular/therapeutic use , COVID-19/epidemiology , COVID-19 Testing , Coinfection/drug therapy , Coinfection/epidemiology , Hospitalization , Humans , Latent Tuberculosis/drug therapy , Male , Middle Aged , Pandemics , Republic of Belarus/epidemiology , Rifampin , Sensitivity and Specificity , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology
10.
Eur J Public Health ; 32(4): 643-647, 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1758732

ABSTRACT

BACKGROUND: The COVID-19 pandemic could have negative effects on tuberculosis (TB) control. The objective was to assess the impact of the pandemic in contact tracing, TB and latent tuberculosis infection (LTBI) in contacts of patients with pulmonary TB in Catalonia (Spain). METHODS: Contact tracing was carried out in cases of pulmonary TB detected during 14 months in the pre-pandemic period (1 January 2019 to 28 February 2020) and 14 months in the pandemic period (1 March 2020 to 30 April 2021). Contacts received the tuberculin skin test and/or interferon gamma release assay and it was determined whether they had TB or LTBI. Variables associated with TB or LTBI in contacts (study period and sociodemographic variables) were analyzed using adjusted odds ratio (aOR) and the 95% confidence intervals (95% CI). RESULTS: The pre-pandemic and pandemic periods showed, respectively: 503 and 255 pulmonary TB reported cases (reduction of 50.7%); and 4676 and 1687 contacts studied (reduction of 36.1%). In these periods, the proportion of TB cases among the contacts was 1.9% (84/4307) and 2.2% (30/1381) (P = 0.608); and the proportion of LTBI was 25.3% (1090/4307) and 29.2% (403/1381) (P < 0.001). The pandemic period was associated to higher LTBI proportion (aOR = 1.3; 95% CI 1.1-1.5), taking into account the effect on LTBI of the other variables studied as sex, age, household contact and migrant status. CONCLUSIONS: COVID-19 is affecting TB control due to less exhaustive TB and LTBI case detection. An increase in LTBI was observed during the pandemic period. Efforts should be made to improve detection of TB and LTBI among contacts of TB cases.


Subject(s)
COVID-19 , Latent Tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , COVID-19/epidemiology , Contact Tracing , Humans , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Pandemics , Tuberculin Test , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology
12.
Reumatismo ; 73(4)2022 Feb 07.
Article in English | MEDLINE | ID: covidwho-1674966

ABSTRACT

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C) is a new acute-onset systemic inflammatory disease, which mainly affects children. Latent tuberculosis infection (LTBI) is characterized by the presence of immune sensitization to Mycobacterium tuberculosis (MTB) in the absence of any clinical or radiological evidence of active disease. We present a child with MIS-C related to COVID-19, with latent TB in the bone marrow, and satisfactory response to tocilizumab. It is important to pay attention in the investigation of TB cases in countries with a high prevalence of tuberculosis, especially when opting for immunusuppression.


Subject(s)
COVID-19 , Latent Tuberculosis , Antibodies, Monoclonal, Humanized , Bone Marrow , COVID-19/complications , COVID-19/drug therapy , Child , Humans , Latent Tuberculosis/complications , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
13.
Cytokine ; 150: 155785, 2022 02.
Article in English | MEDLINE | ID: covidwho-1568622

ABSTRACT

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative individuals with SARS-CoV-2 seropositivity and healthy control (both LTBI and SARS-CoV-2 negative) individuals. Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG +) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1ß, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB - antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.


Subject(s)
COVID-19/complications , Cytokines/blood , Latent Tuberculosis/complications , SARS-CoV-2/immunology , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antigens, Bacterial/immunology , COVID-19/immunology , Chemokines/blood , Female , Humans , Immunocompromised Host , Immunoglobulin G/blood , Inflammation , Latent Tuberculosis/blood , Latent Tuberculosis/immunology , Lymphocyte Activation/drug effects , Male , Middle Aged , Phytohemagglutinins/pharmacology , Seroconversion
14.
BMC Public Health ; 21(1): 2172, 2021 11 26.
Article in English | MEDLINE | ID: covidwho-1538068

ABSTRACT

BACKGROUND: Enhancing tuberculosis (TB) prevention and care in a post-COVID-19-pandemic phase will be essential to ensure progress towards global TB elimination. In low-burden countries, asylum seekers constitute an important high-risk group. TB frequently arises post-immigration due to the reactivation of latent TB infection (LTBI). Upon-entry screening for LTBI and TB preventive treatment (TPT) are considered worthwhile if targeted to asylum seekers from high-incidence countries who usually present with higher rates of LTBI. However, there is insufficient knowledge about optimal incidence thresholds above which introduction could be cost-effective. We aimed to estimate, among asylum seekers in Germany, the health impact and costs of upon-entry LTBI screening/TPT introduced at different thresholds of country-of-origin TB incidence. METHODS: We sampled hypothetical cohorts of 30-45 thousand asylum seekers aged 15 to 34 years expected to arrive in Germany in 2022 from cohorts of first-time applicants observed in 2017-2019. We modelled LTBI prevalence as a function of country-of-origin TB incidence fitted to data from observational studies. We then used a probabilistic decision-analytic model to estimate health-system costs and quality-adjusted life years (QALYs) under interferon gamma release assay (IGRA)-based screening for LTBI and rifampicin-based TPT (daily, 4 months). Incremental cost-effectiveness ratios (ICERs) were calculated for scenarios of introducing LTBI screening/TPT at different incidence thresholds. RESULTS: We estimated that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5% (95% uncertainty interval: 14.2-21.6%) will be latently infected. Introducing LTBI screening/TPT above 250 per 100,000 country-of-origin TB incidence would gain 7.3 (2.7-14.8) QALYs at a cost of €51,000 (€18,000-€114,100) per QALY. Lowering the threshold to ≥200 would cost an incremental €53,300 (€19,100-€122,500) per additional QALY gained relative to the ≥250 threshold scenario; ICERs for the ≥150 and ≥ 100 thresholds were €55,900 (€20,200-€128,200) and €62,000 (€23,200-€142,000), respectively, using the next higher threshold as a reference, and considerably higher at thresholds below 100. CONCLUSIONS: LTBI screening and TPT among 15- to 34-year-old asylum seekers arriving in Germany could produce health benefits at reasonable additional cost (with respect to international benchmarks) if introduced at incidence thresholds ≥100. Empirical trials are needed to investigate the feasibility and effectiveness of this approach.


Subject(s)
COVID-19 , Latent Tuberculosis , Refugees , Adolescent , Adult , Cost-Benefit Analysis , Humans , Incidence , Latent Tuberculosis/diagnosis , Latent Tuberculosis/drug therapy , Latent Tuberculosis/epidemiology , Mass Screening , SARS-CoV-2 , Tuberculin Test , Young Adult
15.
J Mother Child ; 25(2): 127-134, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1498444

ABSTRACT

Various guidelines are in place for management for COVID-19 and pulmonary tuberculosis (PTB) in pregnancy. However, to the best of our knowledge, there are no significant guidelines for the management of COVID-19 and PTB co-infection in pregnancy. Pregnancy being an altered physiological state, the use of various drugs and their outcomes are altered. Here we present two cases of COVID-19 and PTB co-infection in pregnancy which were managed successfully.


Subject(s)
COVID-19 , Coinfection , Latent Tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , COVID-19/complications , Coinfection/diagnosis , Female , Humans , Pregnancy , Tuberculosis/complications , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy
17.
J Clin Microbiol ; 59(10): e0141421, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1430162

ABSTRACT

Interferon gamma release assays are used to screen various patient populations for latent tuberculosis infection. In this issue of the Journal of Clinical Microbiology, J. D. Ward, C. Cornaby, and J. L. Schmitz (J Clin Microbiol 59:e00811-21, 2021, https://doi.org/10.1128/JCM.00811-21) investigated an increased indeterminate rate in the QuantiFERON-TB Gold Plus assay among COVID-19 patients that was independent of immunosuppressive agents and lymphopenia. In their study, COVID-19 patients with indeterminate QuantiFERON-TB Gold Plus results trended toward decreased survival as well as increased serum interleukin-6 (IL-6) and IL-10 levels, although the differences were not statistically significant. They suggest that this pattern of cytokine expression supports an impairment of Th1, specifically interferon gamma production, in critically ill COVID-19 patients, as indicated by indeterminate QuantiFERON-TB Gold Plus results. Clinicians should be aware of the increased rate of indeterminate QuantiFERON-TB Gold Plus results in critically ill COVID-19 patients.


Subject(s)
COVID-19 , Latent Tuberculosis , Humans , Interferon-gamma Release Tests , Interleukin-10 , Latent Tuberculosis/diagnosis , SARS-CoV-2
18.
J Clin Microbiol ; 59(10): e0081121, 2021 09 20.
Article in English | MEDLINE | ID: covidwho-1430153

ABSTRACT

SARS-CoV-2 is a novel positive-sense single-stranded RNA virus that has caused a recent pandemic. Most patients have a mild disease course, while approximately 20% have moderate to severe disease, often requiring hospitalization and, in some cases, care in the intensive care unit. By investigating a perceived increased rate of indeterminate QuantiFERON-TB Gold Plus results in hospitalized COVID patients, we demonstrate that severely ill COVID-19 patients have at least a 6-fold reduction of interferon gamma (IFN-γ) levels compared to control patients. What is more, over 60% of these severely ill COVID-19 patients' peripheral T cells were found to be unable to produce measurable IFN-γ when stimulated with phytohemagglutinin (PHA), a potent IFN-γ mitogen, reflected by an indeterminate QuantiFERON-TB Gold Plus result. This defect of IFN-γ production was independent of absolute lymphocyte counts and immunosuppressive therapy. It was associated with increased levels of interleukin-6 (IL-6), which was a predictor of patient outcomes for our cohort when measured early in the course of disease. Finally, in a subset of COVID-19 patients, we found elevated IL-10 levels in addition to IL-6 elevation. In addition to finding a significant limitation of interferon-gamma release assay (IGRA) testing in severely ill COVID-19 patients, these data provide evidence that many of these patients demonstrate a focused Th2 immune response with inhibition of IFN-γ signaling and, in many cases, significant elevations of IL-6.


Subject(s)
COVID-19 , Latent Tuberculosis , Humans , Interferon-gamma , Interferon-gamma Release Tests , SARS-CoV-2
19.
J Infect ; 83(3): 339-346, 2021 09.
Article in English | MEDLINE | ID: covidwho-1386050

ABSTRACT

OBJECTIVES: Latent Tuberculosis infection (LTBI) is postulated to modulate immune responses and alter disease severity in SARS-CoV-2 co-infection. However, no data exist on the effect of LTBI on the immune responses in SARS-CoV-2 co-infected individuals. METHODS: We examined the SARS-CoV-2 specific antibody responses, plasma cytokines, chemokines, acute phase proteins and growth factor levels in LTBI positive and negative individuals with SARS-CoV-2 infection. RESULTS: Our results demonstrated that individuals with LTBI (LTBI+) and seropositive for SARS-CoV-2 infection were associated with elevated SARS-CoV-2 specific IgM, IgG and IgA antibodies, as well as enhanced neutralization activity compared to those negative for LTBI (LTBI-) individuals. Our results also demonstrate that LTBI+ individuals exhibited significantly higher plasma levels of IFNγ, IL-2, TNFα, IL-1α, IL-1ß, IL-6, IL-12, IL-15, IL-17, IL-3, GM-CSF, IL-10, IL-25, IL-33, CCL3 and CXCL10 compared to LTBI- individuals. Finally, our results show that LTBI+ individuals exhibit significantly higher levels of C-reactive protein, alpha-2 macroglobulin, VEGF and TGFα compared to LTBI- individuals. CONCLUSIONS: Thus, our data clearly demonstrates that LTBI+ individuals seropositive for SARS-CoV-2 infection exhibit heightened levels of humoral, cytokine and acute phase responses compared to LTBI- individuals. Thus, LTBI is associated with modulation of antibody and cytokine responses as well as systemic inflammation in individuals seropositive for SARS-CoV-2 infection.


Subject(s)
COVID-19 , Coinfection , Latent Tuberculosis , Acute-Phase Reaction , Cytokines , Humans , Latent Tuberculosis/complications , SARS-CoV-2
20.
Mikrobiyol Bul ; 55(3): 300-310, 2021 Jul.
Article in Turkish | MEDLINE | ID: covidwho-1368006

ABSTRACT

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide, some issues such as the uncertainty of the disease progress, whether intensive care will be needed, and risk classification are still important for clinicians. It is notable that in countries where latent tuberculosis infection (LTBI) is common and participating in the national Bacillus Calmette-Guerin (BCG) vaccination program, the case-fatality rates are relatively low throughout the world. In this study, it was aimed to evaluate the effects of the BCG vaccine and LTBI status on the course of the disease in patients diagnosed with coronavirus-19 (COVID-19) infection and to compare the LTBI rate with people with and without COVID-19 infection. The patients diagnosed with COVID-19 infection who were hospitalized during a period of seven months between May 1st to December 1st, 2020 were investigated by the QuantiFERON-TB Gold Plus (QFT-Plus) test in the blood samples for the presence of LTBI. For the comparison of the patients diagnosed with COVID-19 and people without COVID-19 infections in terms of LTBI rate retrospectively; all consecutive patients who were sent blood samples to the mycobacteriology laboratory for the QFT-Plus test between January 2016 and December 2019 were included in the study. Demographic, clinical, radiological, laboratory, and follow-up data of the patients were obtained from the electronic patient file. A total of 170 patients (n= 9 8 male [57.6%], n= 72 female [42.3%], mean age= 53.5 ± 15.8 years) were enrolled. Twenty-five patients' (25/170 [14.7%]) QFT-plus tests were positive. When the cases with positive QFT-Plus test (n= 25) and the cases with negative QFT-Plus test (n = 145) were compared in terms of disease severity respectively; it was determined that mild/moderate patients were 18/25 (72%) and 108/145 (74.5%), severe patients were 7/25 (28%) and 37/145 (25.5%) (p= 0.988). When these two groups were compared in terms of the clinical course respectively; the need for intensive care was 6/25 (24%) and 34/145 (23.4%) (p= 1.00), oxygen therapy requirement was 13/25 (52%) and 49/145 (33.8%) (p= 0.128), and death was 5/25 (20%) and 18/145 (12.4%) (p= 0.341). QFT-Plus positivity was 25/170 (14.7%) in patients diagnosed with COVID-19, while in control group it was 198/496 (39.9%) (OR= 0.259, 95% CI [0.164-0.411], p<0.001). When the values were evaluated quantitatively, in the COVID-19 patient group, QFT-Plus T1/T2 (IU/ml) interferon (IFN)-É£ was 0.87 ± 1.52/0.62 ± 1.53, while in the control group it was 1.52 ± 3.69/1.50 ± 3.33 (p= 0.032, p= 0.04). There was no significant difference in the parameters investigated between 82 (48.2%) patients with BCG vaccine and those 88 (51.8%) without BCG vaccine. Although it was not statistically significant in our study, increased oxygen therapy requirement and higher mortality rates in the QFT-Plus positive group were remarkable. The detection of statistically significantly lower LTBI rates and T1-T2/IFN-É£ values in the COVID-19 group supported that SARS-CoV-2 infection may suppress lymphocyte functions in patients and IFN-É£ response. We believe that the results of our study are remarkably valuable, but more clinical studies are needed to elucidate the relationship between BCG vaccine, LTBI, and COVID-19 infection.


Subject(s)
COVID-19 , Latent Tuberculosis , Adult , Aged , BCG Vaccine , Female , Humans , Interferon-gamma Release Tests , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
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