ABSTRACT
Background. Tuberculosis in prisons was reported to be 100 times higher than the normal population. Late diagnosis, overcrowding, and poor ventilation encourage the transmission of tuberculosis. Five percent of new tuberculosis infections turn into active disease within two years. This study was conducted to determine the incidence of tuberculosis infection among new prisoners in southern Thailand. Methods. A prospective cohort study was planned for January 2020-December 2021 at Songkhla Provincial Prison. However, due to the emerging COVID-19 pandemic, the study was terminated early in February 2021. All new prisoners aged >=15 years were included. Subjects were excluded if they had any history of a previous diagnosis of tuberculosis, household contact with a tuberculosis patient, or a history of repeated imprisonment. Chest radiography together with a 2-step tuberculin skin test (TST) was done within 2 weeks after imprisonment and at 6 months using the onestep TST. A positive TST was defined by a skin reaction >=1.5 cm. Prisoners with negative TST had a repeat TST at 6 months. New tuberculosis infection was defined by conversion of TST to positive after 6 months of imprisonment without evidence of active tuberculosis from chest radiography. Results. The number of new prisoners during the study period was 602. All prisoners were men with an average age of 31.11 (range 18-75) years Fifty-one prisoners were excluded. Three hundred and eighty-five prisoners completed the 2-step TST. A total of 11.07% (61/551) of subjects had initially tested positive. Three hundred and seventy prisoners were followed. The COVID-19 pandemic caused a total shutdown of the study because access to the prison was blocked. Therefore, only 53 (9.6%) prisoners completed the study protocol at 6 months. Five prisoners (9.4%) were tuberculin converters with no evidence of active tuberculosis from chest radiography Conclusion. The incidence of tuberculosis infection in new prisoners was 9.4%. This study has limitations. Due to the emerging COVID-19 pandemic, 90.4% of subjects were lost to follow-up and some prisoners were released before 6 months, which caused low power of the study. Further studies are needed to identify the incidence of new tuberculosis infection in new prisoners.
ABSTRACT
The vascular endothelial injury occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but the mechanisms are poorly understood. We sought to determine the frequency and type of cytokine elevations and their relationship to endothelial injury induced by plasma from patients with SARS-CoV-2 versus controls. Plasma from eight consecutively enrolled patients hospitalized with acute SARS-CoV-2 infection was compared to controls. Endothelial cell (EC) barrier integrity was evaluated using ECIS (electric cell-substrate impedance sensing) on human lung microvascular EC. Plasma from all SARS-CoV-2 but none from controls decreased transendothelial resistance to a greater degree than that produced by tumor necrosis factor-alpha (TNF-alpha), the positive control for the assay. Thrombin, angiopoietin 2 (Ang2), and vascular endothelial growth factor (VEGF), complement factor C3a and C5a, and spike protein increased endothelial permeability, but to a lesser extent and a shorter duration when compared to SARS-CoV-2 plasma. Analysis of Ang2, VEGF, and 15 cytokines measured in plasma revealed striking patient-to-patient variability within the SARS-CoV-2 patients. Pretreatment with thrombin inhibitors, single, or combinations of neutralizing antibodies against cytokines, Ca3 and C5a receptor antagonists, or with ACE2 antibody failed to lessen the SARS-CoV-2 plasma-induced EC permeability. The EC barrier destructive effects of plasma from patients with SARS-CoV-2 were susceptible to heat inactivation. Plasma from patients hospitalized with acute SARS-CoV-2 infection uniformly disrupts lung microvascular integrity. No predicted single, or set of, cytokine(s) accounted for the enhanced vascular permeability, although the factor(s) were heat-labile. A still unidentified but potent circulating factor(s) appears to cause the EC disruption in SARS-CoV-2 infected patients. IMPORTANCE Lung vascular endothelial injury in SARS-CoV-2 patients is one of the most important causes of morbidity and mortality and has been linked to more severe complications including acute respiratory distress syndrome (ARDS) and subsequent death due to multiorgan failure. We have demonstrated that in eight consecutive patients with SARS-CoV-2, who were not selected for evidence of endothelial injury, the diluted plasma-induced intense lung microvascular damage, in vitro. Known endothelial barrier-disruptive agents and proposed mediators of increased endothelial permeability in SARS-CoV-2, induced changes in permeability that were smaller in magnitude and shorter in duration than plasma from patients with SARSCoV-2. The effect on endothelial cell permeability of plasma from patients with SARS-CoV-2 was heat-labile. The main plasma factor that causes the increased endothelial permeability remains to be identified. Our study provides a possible approach for future studies to understand the underlying mechanisms leading to vascular injury in SARS-CoV-2 infections.