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Summary: Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology. Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC. We assessed tryptophan and its degradation products by UPLC-MS/MS. IDO2 activity, its potential consequences, and the involvement of the aryl hydrocarbon receptor (AHR) in IDO2 expression were determined in PBMC from another PASC cohort by immunohistochemistry (IHC) for IDO2, IDO1, AHR, kynurenine metabolites, autophagy, and apoptosis. These PBMC were also analyzed by metabolomics and for mitochondrial functioning by respirometry. IHC was also performed on autopsy brain material from two PASC patients. Findings: IDO2 is expressed and active in PBMC from PASC patients, as well as in brain tissue, long after SARS-CoV-2 infection. This is paralleled by autophagy, and in blood cells by reduced mitochondrial functioning, reduced intracellular levels of amino acids and Krebs cycle-related compounds. IDO2 expression and activity is triggered by SARS-CoV-2-infection, but the severity of SARS-CoV-2-induced pathology appears related to the generated specific kynurenine metabolites. Ex vivo, IDO2 expression and autophagy can be halted by an AHR antagonist. Interpretation: SARS-CoV-2 infection triggers long-lasting IDO2 expression, which can be halted by an AHR antagonist. The specific kynurenine catabolites may relate to SARS-CoV-2-induced symptoms and pathology. Funding: None.

Introduction: In Sierra Leone, access to prostheses is limited due to absence of practical knowledge, materials, trained staff, and high cost. This paper investigates the impact of a 3D printed prosthesis on the health-related quality of life (HRQoL) in prosthesis recipients. Methods: Patients with upper extremity amputations were included in this case study from December 2018 until July 2019. Data on the HRQoL was gathered until April 2020 in Masanga Hospital, central rural Sierra Leone. At two follow-up moments the HRQoL was assessed by applying the standard EQ-5D-5L questionnaire. These two follow-up moments varied between one week and just over a year after receiving the prosthesis. A second patient questionnaire was used to assess prosthesis satisfaction. Results: Seven patients were included. The results of the EQ-5D-5L questionnaire show no deterioration of the HRQoL in any patient and the overall HRQoL increased by almost 20% compared to the null measurement. One patient was lost to follow up after the first re-visit. The responses to the second questionnaire indicated that patients are satisfied with the prosthesis and use it in various situations. Patients often mentioned they feel more included in society when wearing the prosthesis. One patient says wearing the prosthesis helped in accepting the amputation. As a result, enough self-confidence was experienced without the prosthesis and the patients stopped wearing the prosthesis. Discussion: The overall HRQoL in patients wearing a 3D-printed prosthesis increases compared to not wearing one. Assessing the HRQoL at regular intervals is important for the long-term follow-up and to safeguard sustainability and long-term success of this project. Nevertheless, defining the HRQoL is challenging due to cultural differences and misunderstandings. Therefore, the use of alternative questionnaires to define the HRQoL should be investigated. To improve and warrant long-term success, identifying long-term problems is important, and the second questionnaire accounts for this need.

In low tuberculosis incidence regions, tuberculosis is mainly concentrated among hard-to-reach populations like migrants, homeless people, drug or alcohol abusers, prisoners and people living with HIV. To be able to eliminate tuberculosis from these low incidence regions tuberculosis screening and treatment programs should focus on these hard-to-reach populations. Here we discuss the barriers and facilitators of health care-seeking, interventions improving tuberculosis screening uptake and interventions improving treatment adherence in these hard-to-reach populations.