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COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients' ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm 3 ) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500 cells/mm 3 ) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

Once overlooked, awareness of nontuberculous mycobacterial pulmonary disease (NTM-PD) is rapidly rising, in line with increasing prevalence worldwide. The European Respiratory Society (ERS) International Congress 2019, held in Madrid, Spain, provided a platform for invigorating discussions and exciting new research in the field. This article explores approaches being taken to combat NTM-PD with a focus not only on novel prevalence and risk factor data, but also on emerging antimicrobials and their routes of delivery, and other potential treatment options in early clinical development., Competing Interests: Conflict of interest: J.D. Chalmers reports grants and personal fees from AstraZeneca and Boehringer Ingelheim, grants from Gilead Sciences, grants and personal fees from GlaxoSmithKline, grants from Grifols, grants and personal fees from Insmed, and personal fees from Chiesi, Novartis and Zambon, outside the submitted work. Conflict of interest: C. Balavoine has nothing to disclose. Conflict of interest: P.F. Castellotti has nothing to disclose. Conflict of interest: C. Hügel reports personal fees from Boehringer Ingelheim and PulmonX, and nonfinancial support from Mukoviszidose e.V., Gilead, Insmed and Novartis, outside the submitted work. Conflict of interest: A. Payet has nothing to disclose. Conflict of interest: D. Wat reports grants and personal fees from Chiesi and Insmed, and personal fees from GlaxoSmithKline, outside the submitted work. Conflict of interest: G. Rohde reports personal fees from Boehringer Ingelheim, Chiesi, Essex Pharma, GlaxoSmithKline, Grifols, Insmed, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Solvay and Vertex, outside the submitted work., (Copyright ©ERS 2020.)

To tackle the tuberculosis (TB) epidemic, in 2014 the World Health Organization launched the End TB Strategy, which includes action to prevent latent TB infection (LTBI) reactivation. Available preventive treatments (PT) are based on either isoniazid (INH) alone or rifampicin (RIF)-containing regimens. This study aims to assess and compare PT completion rates, the occurrence of adverse events, and the time of dropout among those receiving INH-alone or RIF-containing regimens at Villa Marelli Institute, Milan, Italy, covering the period from 1992 to 2018. A total of 19670 subjects, belonging to various risk groups-mainly young (median age of 29 years), foreign-born (73.3%), and males (58.8%)-with presumed LTBI were prescribed PT (79.3% INH-alone and 20.7% RIF-containing regimens). The treatment completion rate was 79.4% on average, with higher rates among those receiving RIF-containing regimens (85.6%) compared to those that were prescribed INH-alone (77.8%) ( p < 0.0001). Notably, some of the high-risk groups for progression of LTBI were more likely to complete PT from RIF-containing regimens. These groups included recent TB contact (89.9%, p < 0.0001), healthcare workers (93.5%, p < 0.0001), and homeless people (76.6%, p < 0.0001). Irrespectively of the chosen PT regimen, most of the dropouts occurred between the start of the treatment and the first follow-up visit (14.3%, 15.2% for those on INH-alone vs. 11.1% for those on RIF-containing regimens). Further shortening of the PT regimen is therefore an aim to ensure adherence, even though it might need further efforts to enhance the patient's attitude towards starting and carrying out PT., Competing Interests: The authors declare no conflict of interest.

In countries of the European Union, tuberculosis (TB) mainly affects marginalised people, including asylum seekers. Migratory flows from high-incidence countries to Italy have increased up to 2017, posing challenges to the national health system. This study sought to assess TB and latent TB infection (LTBI) prevalence among asylum seekers in Milan during the biennium 2016-2017 and to evaluate interventions in place.A two-level active surveillance and screening system was developed for both TB and LTBI. Asylum seekers underwent an initial screening with a tuberculin skin test (TST) and a questionnaire at the receiving sites. At the Regional TB Reference Centre, those with a positive result underwent chest radiography. People aged <35 years with negative chest radiography results underwent further testing by interferon-γ release assay. If results of the assay were positive, LTBI treatment was offered. TB and LTBI prevalence were compared with literature data.A total of 5324 asylum seekers, mostly young (10-39 years; 98%), male (84%) and from sub-Saharan Africa (69%), were enrolled in the study. 69 active TB cases were diagnosed and 863 LTBI-positive individuals were detected. TB prevalence was high (1236 per 100 000 population) and LTBI prevalence was 28%. Despite losses (41%) during the transition from initial screening sites and the diagnostic centre, a good TB cure rate (84%) and optimal LTBI treatment completion (94%) were achieved.Our study shows that TB incidence is high among asylum seekers in Milan and that well-coordinated screening measures are critical for early diagnosis and treatment. It also proves that rolling out successful at-scale interventions for both prophylaxis and disease management is feasible., Competing Interests: Conflict of interest: S. Villa has nothing to disclose. Conflict of interest: L.R. Codecasa has nothing to disclose. Conflict of interest: M. Faccini has nothing to disclose. Conflict of interest: M.M. Pontello has nothing to disclose. Conflict of interest: M. Ferrarese has nothing to disclose. Conflict of interest: P.F. Castellotti has nothing to disclose. Conflict of interest: S. Senatore has nothing to disclose. Conflict of interest: A. Lamberti has nothing to disclose. Conflict of interest: E. Mazzola has nothing to disclose. Conflict of interest: C.F. Perno has nothing to disclose. Conflict of interest: D. Campisi has nothing to disclose. Conflict of interest: M. Saporiti has nothing to disclose. Conflict of interest: M.C. Raviglione has nothing to disclose., (Copyright ©ERS 2019.)

Setting: Screening for latent tuberculous infection (LTBI) of groups at high risk of active tuberculosis (TB) is a key component of the End TB Strategy., Objective: To conduct a retrospective descriptive analysis of LTBI rates among foreign-born individuals applying to shelters in the metropolitan area of Milan, Italy., Design: All foreign-born individuals registering for accommodation centres in the city of Milan from November 2009 to April 2017 were screened for active TB and LTBI. Individuals aged <36 years with a tuberculin skin test (TST) induration of >10 mm were offered confirmatory testing with QuantiFERON®-TB Gold In-Tube (QFT-GIT)., Results: Of the 2666 TST-positive migrants aged <36 years who underwent LTBI confirmation testing, 1322 (49.6%) tested negative, 1339 (50.2%) were positive and five (0.2%) had indeterminate results. In the multivariate analysis, TB incidence in the country of origin and age were significantly associated with QFT-GIT positivity. Although estimated TB incidence in Eritrea, Morocco and Romania was 100/100 000 person-years (py), the probability of being QFT-GIT-positive in individuals from these countries were not statistically significantly different from individuals from countries with TB incidence > 250/100 000 person-years., Conclusion: Our data showed a high proportion of LTBI among individuals coming from intermediate TB burden countries.

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4 + and CD8 + T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2-TB1) was used as an estimate of CD8 + stimulation provided by the TB2. TB2-TB1 values >0.6 IU·mL -1 were significantly associated with proximity to the index case and European origin.QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8 + response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection., (Copyright ©ERS 2016.)