Prevalence of Latent Tuberculosis Infection among Patients Undergoing Regular Hemodialysis in Disenfranchised Communities: A Multicenter Study during COVID-19 Pandemic.

Background and Objectives: Due to their weakened immune response, hemodialysis (HD) patients with latent tuberculosis infection (LTBI) are at higher risk for active tuberculosis (TB) disease and are more subject to patient-to-patient transmission within dialysis units. Consequently, current guidelines advocate screening these patients for LTBI. To our knowledge, the epidemiology of LTBI in HD patients has never been examined before in Lebanon. In this context, this study aimed to determine LTBI prevalence among patients undergoing regular HD in Northern Lebanon and to identify potential factors associated with this infection. Notably, the study was conducted during the COVID-19 pandemic, which is likely to have catastrophic effects on TB and increase the risk of mortality and hospitalization in HD patients. Materials and Methods: A multicenter cross-sectional study was carried out in three hospital dialysis units in Tripoli, North Lebanon. Blood samples and sociodemographic and clinical data were collected from 93 HD patients. To screen for LTBI, all patient samples underwent the fourth-generation QuantiFERON-TB Gold Plus assay (QFT-Plus). Multivariable logistic regression analysis was used to identify the predictors of LTBI status in HD patients. Results: Overall, 51 men and 42 women were enrolled. The mean age of the study population was 58.3 ± 12.4 years. Nine HD patients had indeterminate QFT-Plus results and were therefore excluded from subsequent statistical analysis. Among the remaining 84 participants with valid results, QFT-Plus was positive in 16 patients, showing a positivity prevalence of 19% (95% interval for p: 11.3%, 29.1%). Multivariable logistic regression analysis showed that LTBI was significantly associated with age [OR = 1.06; 95% CI = 1.01 to 1.13; p = 0.03] and a low-income level [OR = 9.29; 95% CI = 1.62 to 178; p = 0.04]. Conclusion: LTBI was found to be prevalent in one in five HD patients examined in our study. Therefore, effective TB control measures need to be implemented in this vulnerable population, with special attention to elderly patients with low socioeconomic status.

Reactivation of latent tuberculosis in a COVID-19 patient on corticosteroid treatment.

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.

Multisystemic inflammatory syndrome related to COVID-19, with latent tuberculosis in bone marrow, and satisfactory response to tocilizumab, in a 7-year-old boy.

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.

Effect of SARS-CoV-2 seropositivity on antigen - specific cytokine and chemokine responses in latent tuberculosis.

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.

Latent tuberculosis co-infection is associated with heightened levels of humoral, cytokine and acute phase responses in seropositive SARS-CoV-2 infection.

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.

Biologic Treatment Algorithms for Moderate-to-Severe Psoriasis with Comorbid Conditions and Special Populations: A Review.

The emergence of data from clinical trials of biologics, the approval of new biologics, and our improved understanding of psoriasis pathogenesis have increased the therapeutic possibilities for the treatment of moderate-to-severe psoriasis. Biologics currently approved for the treatment of psoriasis include tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors, ustekinumab (an IL-12/23 inhibitor), and IL-23 inhibitors. Data from clinical trials and studies of the safety and efficacy of biologics provide essential information for the personalization of patient care. We discuss the benefits and disadvantages of biologics as a first-line treatment choice, update treatment recommendations according to current evidence, and propose psoriasis treatment algorithms. Our discussion includes the following comorbid conditions: psoriatic arthritis, multiple sclerosis, congestive heart failure, inflammatory bowel disease, hepatitis B, nonmelanoma skin cancer, lymphoma, and latent tuberculosis. We make evidence-based treatment recommendations for special populations, including pediatric patients, patients with coronavirus 2019 (COVID-19), and pregnant and breastfeeding patients with psoriasis. Ultimately, individualized recommendations that consider patient preferences, disease severity, comorbid conditions, and additional risk factors should be offered to patients and updated as new trial data emerges.

Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV.

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.

Role of latent tuberculosis infections in reduced COVID-19 mortality: Evidence from an instrumental variable method analysis.

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there has been significant interest in the potential protective effect of the Bacillus Calmette-Guerin (BCG) vaccine against COVID-19 mortality. This effect has been attributed to innate immune responses induced by BCG vaccination. However, these studies ignore an important fact: according to World Health Organization estimates, about a quarter of the world's population may have latent tuberculosis infection (LTBI), a condition in which there is no evidence of clinically active tuberculosis but persistent immune responses are stimulated by Mycobacterium tuberculosis antigens. Thus, both LTBI and BCG induce lifelong immunity and may provide immunological protection against COVID-19. In this study, the relationship between LTBI and reduced COVID-19 mortality was analyzed using the instrumental variable method. The results showed with robust statistical support that LTBI was also associated with reduced COVID-19 mortality.