Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.

BACKGROUND: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. METHODS: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. RESULTS: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). CONCLUSIONS: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study.

Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors in some severe cases have not been identified. Lymphocytopenia has been frequently described in CAP. Since IL-7, membrane-bound receptor (IL7Rα;CD127) and soluble IL7Rα (sIL7R) are critical in lymphocytes homeostasis, in this work we aimed to evaluate the involvement of the IL-7/IL7Rα axis in the severity of adult CAP, since it has not been explored. The IL7Rα SNPs rs6897932, rs987106, and rs3194051 SNPs in IL7α were genotyped, the systemic expression of the IL7R gene, sIL7R, IL-7, and levels of peripheral IL7Rα+ T lymphocytes were quantified in 202 hospitalized CAP cases. rs3194051GG was more frequent in non-survivors than in survivors; rs987106TT was more frequent and rs3194051AA less frequent in patients at intensive care unit (ICU) than in those not admitted to ICU. IL7Rα gene expression was lower in non-survivors than in survivors, and in severe than in mild cases. CD3+CD127+ lymphocytes were lower in severe than in mild cases; in non-survivors than in survivors and in ICU than in non- ICU admitted cases. sIL7Rα plasmatic levels were higher in non-survivors than in survivors, and in severe than in mild cases. rs6897932CC, rs987106AA and rs3194051GG carriers showed the highest while rs6897932TT showed the lowest sIL7Rα levels. The AUC of sIL7Rα levels predicting 30-day mortality was 0.71. Plasma IL-7 levels were lower in ICU-admitted than in not ICU-admitted and in non-survivors than in survivors. No additional association was detected. In conclusion, rs3194051GG and rs987106TT IL7R genotypes were associated with a poorer prognosis. A significant association between sIL7R levels and SNPs of the IL7R gene is described for the first time in adult CAP. Increased plasmatic sIL7R could contribute to identifying adult CAP cases at risk of death.

Rendimiento de dos índices predictores de mortalidad (PSI y CURB-65) en pacientes adultos inmunocompetentes hospitalizados por neumonía adquirida en la comunidad / Yield of two mortality predictors in immunocompetent patients with community acquired pneumonia

Background: The severity of community acquired pneumonia (CAP) can be evaluated by the PSI and CURB-65 scales. However, it is unknown whether their predictive capacity varies according to the etiology of the disease. Aim: To compare the performance of these scales in adults with viral, bacterial, mixed, and no agent detected CAP. Material and Methods: We studied 725 patients hospitalized for CAP aged 18 to 95 years (47% females) Urinary S. pneumoniae and Legionella antigens were detected by immuno-chromatography (Binax®). Respiratory viruses and bacteria were detected by PCR in nasopharyngeal smears. The proportions of deaths, admission to the intensive care unit (ICU), and oxygen therapy were compared between mild and non-severe patients defined by PSI (I/II and I-III) and CURB-65 (1 and 1-2), according to the causative agent. Results: Ten percent of patients died. A causative agent was detected in 65%. The proportion of mild and non-severe patients according to PSI and CURB-65, and of deceased patients, admitted to the ICU and with oxygen therapy was similar in the four categories per agent. There were no deaths among non-severe patients with bacterial CAP. However, 6% of patients with CAP caused by virus or without causative agents, died. No deaths occurred among mild patients with bacterial CAP. In viral CAP, no deaths occurred among patients classified as mild only by PSI. The yields of PSI were greater than those of CURB-65 in non-severe patients who died and were admitted to the ICU with bacterial and viral CAP (5 and 14%; 7 and 12% respectively, p = 0.04). Conclusions: The prognostic performance of PSI in CAP varies according to the causative agent in adults. It is higher in non-severe bacterial cases, and superior to CURB-65.

Cyclovirus detection in Chilean adults with and without community-acquired pneumonia.

Cycloviruses (CyV) (genus Cyclovirus, family Circoviridae) are nonenveloped DNA viruses. The first report in humans was in 2010 and research has focused only on disease-associated human sample detection. The only HuACyV (CyCV-ChileNPA1, HuACyV10) reported in the Chilean population was in children (3.3%) with an acute respiratory infection. Its detection in respiratory samples from adults, with/without respiratory disease remains unknown. The aim of this study was to detect HuACyV10 in adults with and without respiratory disease. HuACyV10 was studied in nasopharyngeal swabs from 105 hospitalized adults with community-acquired pneumonia (CAP) and 104 adults without respiratory symptoms. Total nucleic acids were extracted, and viral rep and cp gene fragments were amplified by real-time polymerase chain reaction. HuACyV10 was detected in 19.05% adults with CAP and in 0.96% asymptomatic adults, being significantly higher in adult CAP than asymptomatic (n = 1) ones (p = 0.0001). C t values were between 26.7 and 39.6, and the median was 34.1 for rep and 33.8 for the CAP in adults CAP (p = 0.68), and 35.7 and 36.0, respectively, in the asymptomatic case. HuACyV10 detection in CAP adults concentrated in the Autumn-Winter season of the Southern hemisphere. The only asymptomatic adult with HuACyV10 was detected in the Spring-Summer period. In this first report of HuACyV10 in respiratory samples from adults, detection was significantly higher in CAP than in asymptomatic adults. As the sensitivity of both rep and cp genes was similar, both can be applied for detecting HuACyV10. It would be advisable to investigate the pathogenic role of HuACyV10 in adult respiratory infections. ​.

[Yield of two mortality predictors in immunocompetent patients with community acquired pneumonia]. / Rendimiento de dos índices predictores de mortalidad (PSI y CURB-65) en pacientes adultos inmunocompetentes hospitalizados por neumonía adquirida en la comunidad.

BACKGROUND: The severity of community acquired pneumonia (CAP) can be evaluated by the PSI and CURB-65 scales. However, it is unknown whether their predictive capacity varies according to the etiology of the disease. AIM: To compare the performance of these scales in adults with viral, bacterial, mixed, and no agent detected CAP. MATERIAL AND METHODS: We studied 725 patients hospitalized for CAP aged 18 to 95 years (47% females) Urinary S. pneumoniae and Legionella antigens were detected by immuno-chromatography (Binax®). Respiratory viruses and bacteria were detected by PCR in nasopharyngeal smears. The proportions of deaths, admission to the intensive care unit (ICU), and oxygen therapy were compared between mild and non-severe patients defined by PSI (I/II and I-III) and CURB-65 (1 and 1-2), according to the causative agent. RESULTS: Ten percent of patients died. A causative agent was detected in 65%. The proportion of mild and non-severe patients according to PSI and CURB-65, and of deceased patients, admitted to the ICU and with oxygen therapy was similar in the four categories per agent. There were no deaths among non-severe patients with bacterial CAP. However, 6% of patients with CAP caused by virus or without causative agents, died. No deaths occurred among mild patients with bacterial CAP. In viral CAP, no deaths occurred among patients classified as mild only by PSI. The yields of PSI were greater than those of CURB-65 in non-severe patients who died and were admitted to the ICU with bacterial and viral CAP (5 and 14%; 7 and 12% respectively, p = 0.04). CONCLUSIONS: The prognostic performance of PSI in CAP varies according to the causative agent in adults. It is higher in non-severe bacterial cases, and superior to CURB-65.

Immunoglobulins concentration and B cell counts as severity markers in adult community-acquired pneumonia: Cross sectional study.

Community-acquired pneumonia (CAP) is a worldwide cause of morbidity and mortality. Immunoglobulins (Igs) and B cells quantification studies in CAP are few and show discrepancies. Serum IgA acts as a powerful natural anti-inflammatory factor, but its role in the CAP has not yet been defined. The highly sensitive xMAP Luminex technique allows better immunoglobulins quantification. The aim of this study was to analyze the relation between clinical severity and circulating Igs and B cells in adults with CAP.Igs (M, A, G1, G2, G3, and G4) and B cells were quantified in peripheral blood of 190 Chilean patients ≥18 years old hospitalized for CAP and in 21 adults without respiratory disease, using xMAP Luminex and flow cytometry, respectively. Clinical history was recorded and PSI and CURB-65 scores were calculated for evaluation of clinical severity.The total IgM, IgG2 and total IgG levels were lower in CAP than in asymptomatic adults (P < .05). No significant differences of Igs levels were found between patients classified as severe and mild by PSI and CURB-65 scores. Fatal cases had higher levels of IgA (P < .05). No differences in CD19 B cells frequency was found between CAP and asymptomatic adults (P = .40). In PSI severe cases, CD19 B cells were significantly lower than in mild cases (P = .008). No differences were found in CURB-65 severe and mild groups (P = .11). In fatal cases (11/82) group, CD19 B cells frequency was lower than in 71 survivors (P = .2). No differences in memory B lymphocytes were detected between asymptomatic and CAP adults, severe and mild patients, survivors and fatal cases (P > .05).Serum IgA levels were significantly higher in fatal CAP cases, raising it as a potential biomarker for severe disease considering its relatively universal availability. In PSI severe patients, B cells showed lower levels and could have a role on its physiopathology. Finding new markers rooted in physiopathology could improve the possibility of scoring severe CAP cases. Luminex technology showed promising quantification serum Igs.

Comparison of Luminex xTAG® RVP fast assay and real time RT-PCR for the detection of respiratory viruses in adults with community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the third cause of death worldwide. Viruses are frequently detected in adult CAP. Highly sensitive diagnostic techniques should be used due to poor viral shedding. Different sampling methods can affect viral detection, being necessary to establish the optimal type of sample for identifying respiratory viruses in adults. The detection rates of respiratory viruses by Luminex xTAG® RVP fast assay, real time RT-PCR (rtRT-PCR) (Sacace®), and immunofluorescence assay (IFA) in adult CAP were performed in nasopharyngeal swabs (NPS) and aspirates (NPA) from 179 hospitalized adults. Positivity was 47.5% for Luminex®, 42.5% for rtRT-PCR (P = 0.3), and 2.7% for IFA (2.7%) (P < 0.0). The sensitivity, specificity, and kappa coefficient of xTAG® RVP compared with rtRT-PCR were 84.2%, 79.6%, and 0.62%, respectively. Luminex® and rtRT-PCR detected 65 (58.0%) and 57 (50.9%) viruses in 112 NPA and 35 (34.3%) and 31 (30.4%) in 102 NPS, respectively (P < 0.01). xTAG® RVP is appropriate for detecting respiratory viruses in CAP adults. Both molecular techniques yielded better results with nasopharyngeal aspirate than swabs.