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To look for the spectrum of infections and the factors predisposing to infection in patients with systemic sclerosis (SSc). In this retrospective study, demographic, clinical features, details of infections, immunosuppressive therapy, and outcomes of patients with SSc attending clinics at department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India from 1990 to 2022 were captured. Multivariable-adjusted logistic regression was applied to identify independent predictors of infection. Data of 880 patients, mean age 35.5 ± 12 years, and female: male ratio 7.7:1, were analyzed. One hundred and fifty-three patients had at least 1 infection with a total of 233 infectious episodes. Infections were most common in lung followed by skin and soft tissue. Tuberculosis was diagnosed in 45 patients (29.4%). Klebsiella was the commonest non-tubercular organism in lung and Escherichia coli in urinary tract infections. In comparison to matched control group, patients with infection had a greater number of admissions due to active disease, odds ratio (OR) 6.27 (CI 3.23-12.18), were receiving immunosuppressive medication OR, 5.05 (CI 2.55-10.00), and had more digital ulcers OR, 2.53 (CI 1.17-5.45). Patients who had infection had more likelihood for death OR, 13.63 (CI 4.75 -39.18). Tuberculosis is the commonest infection and lung remains the major site of infection in patients with SSc. Number of hospital admissions, digital ulcers and immunosuppressive therapy are predictors of serious infection in patients with SSc. Patients with infections had more likelihood of death.
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Study Objectives: Studies have indicated that sleep abnormalities are a strong risk factor for developing cognitive impairment, cardiomyopathies, and neurodegenerative disorders. However, neuroimaging modalities are unable to show any consistent markers in obstructive sleep apnea (OSA) patients. We hypothesized that, compared with those of the control cohort, advanced diffusion MRI metrics could show subtle microstructural alterations in the brains of patients with OSA. Methods: Sixteen newly diagnosed patients with moderate to severe OSA and 15 healthy volunteers of the same age and sex were considered healthy controls. Multishell diffusion MRI data of the brain, along with anatomical data (T1 and T2 images), were obtained on a 3T MRI system (Siemens, Germany) after a polysomnography (PSG) test for sleep abnormalities and a behavioral test battery to evaluate cognitive and executive brain functions. Diffusion MRI data were used to compute diffusion tensor imaging and diffusion kurtosis imaging (DKI) parameters along with white-matter tract integrity (WMTI) metrics for only parallel white-matter fibers. Results: OSA was diagnosed when the patient's apnea-hypopnea index wasâ ≥â 15. No significant changes in cognitive or executive functions were observed in the OSA cohort. DKI parameters can show significant microstructural alterations in the white-matter region, while the WMTI metric, the axonal-water-fraction (fp), reveals a significant decrease in OSA patients concerning the control cohort. Conclusions: Advanced diffusion MRI-based microstructural alterations in the white-matter region of the brain suggest that white-matter tracts are more sensitive to OSA-induced intermittent hypoxia.
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The persistent morbidity and mortality associated with tuberculosis (TB), despite our continued efforts, has been long recognized, and the rise in the incidence of drug-resistant TB adds to the preexisting concern. The bulk of the TB burden is confined to low-income countries, and rigorous efforts are made to detect, notify, and systematically treat TB. Efforts have been infused with renewed vigor and determination by the World Health Organization (WHO) to eliminate tuberculosis in the near future. Different health agencies worldwide are harvesting all possible strategies apart from consolidating ongoing practices, including prevention of the development of active disease by treating latent TB infection (LTBI). The guidelines for the same were already provided by the WHO and were then adapted in the Indian guidelines for the treatment of LTBI in 2021. While the long-term impact of TBI treatment is awaited, in this article, we aim to discuss the implications in the Indian context.
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Background: Computed tomography (CT)-guided biopsy is emerging as a preferred and safe method for obtaining tissue samples in pleural diseases. Objective: This study aimed to evaluate the diagnostic yield and safety of percutaneous CT-guided biopsy in pleural diseases and to find CT findings predictive of malignant neoplastic pleural disease. Material and Methods: This retrospective study included 77 patients with pleural disease who underwent CT-guided pleural biopsies from July 2013 to May 2020. All procedures were performed with a coaxial semi-automatic biopsy device. Histopathology was performed in all cases, and additional tests such as immunohistochemistry (IHC) or microbiological analysis were carried out depending on clinical suspicion. The correlation of CT findings with final diagnosis was performed by Chi-square, Fisher's exact test and logistic regression analysis. Results: The overall technical success rate of CT-guided pleural biopsy was 100% with a diagnostic yield of 96.1%. No major complication was encountered, with minor complications encountered in the form of minimal pneumothorax and chest pain. Malignant pleural conditions constituted the largest group including metastatic adenocarcinoma as the most common (31.2%), followed by metastatic squamous cell carcinoma and mesothelioma. Tubercular pleural involvement was the second most common category (16.9%). The cartridge-based nucleic acid amplification test (CB-NAAT) assay had 90% sensitivity on pleural tissue in tubercular cases. CT features predictive of malignancy were irregular and nodular pleural thickening, mediastinal and diaphragmatic pleural involvement and mediastinal/chest wall invasion. There was a good correlation between higher pleural thicknesses with malignant outcome. Conclusion: Percutaneous CT-guided biopsy is a safe method for obtaining pleural tissue samples with high diagnostic yield. CT findings provide clues, which favour malignant pleural involvement.
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COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment.
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COVID-19 , Aspergilose Pulmonar , Humanos , COVID-19/complicações , Bases de Dados Factuais , Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Aspergilose Pulmonar/complicações , Aspergilose Pulmonar/tratamento farmacológicoRESUMO
Introduction: Patients with coronavirus disease-2019 (COVID-19) are prone to develop respiratory bacterial infections irrespective of their need for mechanical ventilatory support. Hypothesis/Gap Statement: Information about the incidence of concomitant respiratory bacterial infections in COVID- 19 patients from India is limited. Aim: This study aimed to determine the incidence of concomitant respiratory bacterial pathogens and their drug resistance in these patients. Methodology: A prospective study was performed by including patients who were admitted to our tertiary care centre from March 2021 to May 2021 to evaluate secondary bacterial respiratory co-infections in patients via real-time PCR (RT-PCR)-confirmed cases of COVID-19 disease caused by SARS CoV-2. Results: Sixty-nine culture-positive respiratory samples from patients with COVID-19 were incorporated into this study. The most commonly isolated bacterial microorganisms were Klebsiella pneumoniae (23 samples, 33.33â%) and Acinetobacter baumannii (15, 21.73â%), followed by Pseudomonas aeruginosa (13, 18.84â%). Among the microorganisms isolated, 41 (59.4â%) were multidrug-resistant (MDR) and nine (13â%) were extensively drug-resistant (XDR). Among the Gram-negative bacteria isolated, K. pneumoniae showed high drug resistance. Fifty carbapenem-resistant microorganisms were isolated from the patients included in our study. Concerning the hospital stay of the patients enrolled, there was an increased length of intensive care unit stay, which was 22.25±15.42 days among patients needing mechanical ventilation in comparison to 5.39±9.57 days in patients on ambient air or low/high-flow oxygen. Conclusion: COVID-19 patients need increased length of hospitalization and have a high incidence of secondary respiratory bacterial infections and high antimicrobial drug resistance.
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CONTEXT: Systematic assessment of skeletal muscle function is lacking in patients with nonsurgical hypoparathyroidism (HP). Whether muscle dysfunction involves respiratory muscles and results in restrictive lung disease (RLD) is not studied. OBJECTIVE: To assess skeletal muscle and pulmonary functions in patients with HP. DESIGN: Observational case-control study. METHODS: Thirty patients with HP (mean age 37.7 years, 60% males) and 40 age-, sex-, and body mass index (BMI)-matched healthy controls were assessed for skeletal muscle function by handgrip strength, the short physical performance battery (SPPB) test, dual-energy X-ray absorptiometry (DXA), and electromyography (EMG). Pulmonary function was assessed by spirometry, body plethysmography, diffusion lung capacity for carbon monoxide, and diaphragmatic ultrasound (DUS). RESULTS: Patients with HP had lower serum calcium (2.25 ± 0.15 vs 2.4 ± 0.12â mmol/L, P < .001), serum magnesium (median [interquartile range] 0.74 [0.69-0.82] vs 0.78 [0.69-0.90] mmol/L, P = .04), handgrip strength (18.08 ± 8.36 vs 22.90 ± 7.77â kg, P = .01), and composite SPPB scores (9.5 [7-10] vs 12 [12-12], P < .001) compared to healthy controls. Electromyographic evidence of myopathy was seen in 23% (5 of 22) of patients with HP but in none of the controls (P = .08). The prevalence of RLD was higher in the HP cohort compared to that in controls (24% vs 0%, P = .01). Diaphragmatic excursion (DE) (4.22 ± 1.38 vs 5.18 ± 1.53â cm, P = .01) and diaphragmatic thickness (DT) (3.79 ± 1.18 vs 4.28 ± 0.94â mm, P = .05) on deep inspiration were reduced in patients with HP. CONCLUSION: Detailed testing of patients with HP without overt muscle and lung diseases revealed significant impairment in parameters of skeletal muscle function. Myopathy and RLD were observed in a considerable proportion of patients with HP.
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Hipoparatireoidismo , Pneumopatias , Masculino , Humanos , Adulto , Feminino , Estudos de Casos e Controles , Força da Mão , Pneumopatias/complicações , Músculo Esquelético/diagnóstico por imagemRESUMO
INTRODUCTION: There is a dearth of biomarkers in Idiopathic Inflammatory Myopathies (IIM) to recognize ongoing muscle inflammation and distinguish damage from activity. Since IIM is an autoantibody-mediated disease with tertiary lymphoid organogenesis reported in the diseased muscles, we aimed to study the peripheral blood T helper (Th) subset profiling as a plausible reflection of ongoing muscle inflammation. METHODS: Fifty-six patients of IIM were compared with 21 healthy controls (HC) and 18 patients with sarcoidosis. Th1, Th17, Th17.1, and Treg cells were identified after stimulation assays (BD Biosciences). Myositis autoantibodies were tested by line immunoassay (Euroimmune, Germany). RESULTS: All Th subsets were elevated in IIM as compared with HC. As compared to HC, PM had elevated Th1 and Treg while Th17 and Th17.1 populations were higher in OM. Patients with sarcoidosis had higher Th1 and Treg but lower Th17 population as compared to IIM {Th1(69.1% vs 49.65%, p<0.0001), {Treg (12.05% vs 6.2%, p<0.0001), {Th17 (2.49% vs 4.4%, p<0.0001)}. Similar results were obtained when sarcoidosis ILD was compared with IIM ILD with a higher Th1 and Treg population but lower Th17 population in the former. No difference in T cell profile was observed after stratification for MSA positivity, type of MSA, clinical features of IIM and disease activity. CONCLUSION: Th subsets in IIM are distinct from sarcoidosis and HC with a TH17 predominant paradigm, creating a case of exploring Th17 pathway and IL-17 blockers for the treatment of IIM. However, cell profiling cannot distinguish active from inactive disease limiting its predictive potential as a biomarker of activity in IIM.
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Miosite , Sarcoidose , Humanos , Autoanticorpos , Biomarcadores , Inflamação , Estudos Longitudinais , Miosite/diagnóstico , Sarcoidose/diagnósticoRESUMO
BACKGROUND AND AIM: Diffuse alveolar hemorrhage (DAH) is a life-threatening condition due to the extravasation of blood in the alveoli, resulting in hypoxemia and even acute respiratory distress syndrome. This study aimed to describe the clinico-radio-pathological profile of patients diagnosed with DAH and classify it into immune and nonimmune DAH. METHODS: This was a retrospective analytical study. Of a total of 1000 cases of bronchoalveolar lavage fluids (BALF) received for cytological examination, patients fulfilling the clinical, radiological, and laboratory details of cases satisfying the clinical and cytological criteria of DAH (n=47) were studied. RESULTS: The most common cause of immune DAH was ANCA-associated vasculitis (n=13, 27.6%), and that of nonimmune DAH was infections (n=10, 21.3%). Twenty-nine patients (61.7%) had hemoptysis. The most common radiological finding was ground-glass opacities (n=33, 70.2%). In univariate analysis, female sex, mean hemoglobin at admission, total leucocyte count (TLC), platelet count, and erythrocyte sedimentation rate (ESR) were significantly associated with immune-DAH. However, in multivariate analysis, female sex, higher TLC, high platelets, and high ESR were significantly associated with immune DAH. Patients were treated with corticosteroids (n=25, 46.3%), intravenous cyclophosphamide (n=12, 22.2%), plasma exchange (n=7, 13.0%), intravenous immunoglobulin (n=5, 9.3%) and rituximab (n=5, 9.3%). The overall mortality was 8.5% (n=4). CONCLUSIONS: DAH is a life-threatening syndrome that may be classified into immune and nonimmune DAH. Immune-DAH requires aggressive management, whereas nonimmune DAH cases respond best to conservative management.
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Introduction: There is a dearth of biomarkers in Idiopathic Inflammatory Myopathies (IIM) to recognize ongoing muscle inflammation and distinguish damage from activity. Since IIM is an autoantibody-mediated disease with tertiary lymphoid organogenesis reported in the diseased muscles, we aimed to study the peripheral blood T helper (Th) subset profiling as a plausible reflection of ongoing muscle inflammation. Methods: Fifty-six patients of IIM were compared with 21 healthy controls (HC) and 18 patients with sarcoidosis. Th1, Th17, Th17.1, and Treg cells were identified after stimulation assays (BD Biosciences). Myositis autoantibodies were tested by line immunoassay (Euroimmune, Germany). Results: All Th subsets were elevated in IIM as compared with HC. As compared to HC, PM had elevated Th1 and Treg while Th17 and Th17.1 populations were higher in OM. Patients with sarcoidosis had higher Th1 and Treg but lower Th17 population as compared to IIM {Th1(69.1% vs 49.65%, p<0.0001), {Treg (12.05% vs 6.2%, p<0.0001), {Th17 (2.49% vs 4.4%, p<0.0001)}. Similar results were obtained when sarcoidosis ILD was compared with IIM ILD with a higher Th1 and Treg population but lower Th17 population in the former. No difference in T cell profile was observed after stratification for MSA positivity, type of MSA, clinical features of IIM and disease activity. Conclusion: Th subsets in IIM are distinct from sarcoidosis and HC with a TH17 predominant paradigm, creating a case of exploring Th17 pathway and IL-17 blockers for the treatment of IIM. However, cell profiling cannot distinguish active from inactive disease limiting its predictive potential as a biomarker of activity in IIM.(AU)
Introducción: Hay una escasez de biomarcadores en las miopatías inflamatorias idiopáticas (MII) para reconocer la inflamación muscular en curso y distinguir el daño de la actividad. Dado que la MII es una enfermedad mediada por autoanticuerpos con organogénesis linfoide terciaria informada en los músculos enfermos, nuestro objetivo fue estudiar el perfil del subconjunto de linfocitos T helpers (Th) de sangre periférica como un reflejo plausible de la inflamación muscular en curso. Métodos: Se compararon 56 pacientes de MII con 21 controles sanos (CS) y 18 pacientes con sarcoidosis. Las células Th1, Th17, Th17.1 y Treg se identificaron después de los ensayos de estimulación (BD Biosciences). Los autoanticuerpos de miositis se analizaron mediante inmunoanálisis en línea (Euroimmune, Alemania). Resultados: Todos los subconjuntos de Th estaban elevados en las MII en comparación con los CS. En comparación con los CS, PM tenía Th1 y Treg elevados, mientras que las poblaciones de Th17 y Th17.1 eran más altas en OM. Los pacientes con sarcoidosis tenían una población Th1 y Treg más alta pero una población Th17 más baja en comparación con MII {Th1 (69,1% frente a 49,65%, p<0,0001), {Treg (12,05% frente a 6,2%, p<0,0001), {Th17 (2,49% frente a 4,4%, p<0,0001)}. Se obtuvieron resultados similares cuando se comparó la EPI de sarcoidosis con la EPI de las MII con una mayor población Th1 y Treg pero menor población Th17 en la primera. No se observaron diferencias en el perfil de células T después de la estratificación por positividad de MSA, tipo de MSA, características clínicas de las MII y actividad de la enfermedad. Conclusión: Los subconjuntos de Th en las MII son distintos de la sarcoidosis y los CS con un paradigma predominante TH17, lo que crea un caso de exploración de la vía Th17 y los bloqueadores de IL-17 para el tratamiento de las MII...(AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Miosite , Células Th17 , Sarcoidose , Biomarcadores , Doenças Pulmonares Intersticiais , Músculos , Estudo de Prova de Conceito , Estudos de Casos e ControlesRESUMO
Background: Immune dysregulation plays a key role in determining COVID-19 disease severity. We aimed to analyze the T cell activation profile in COVID - 19 cases and its predictive role in disease severity and outcome. Material & methods: This was a prospective observational pilot study from a tertiary care COVID-19 hospital. Peripheral blood samples obtained between the fifth and seventh day of COVID-19 illness, were subjected to lymphocyte subset analysis using multicolor flowcytometry using a single tube, 8 antibodies (CD45, CD19, CD3, CD4, CD8, CD38, HLADR, and CD56) analysis. Correlation between lymphocyte subset analysis and clinical profile was determined. Results: 26 patients including 11 with mild disease and 15 with severe disease were enrolled. The median age was 58 years (range: 33-81), with a male: female ratio of 1.36:1. Significant lymphopenia was observed in the severe group compared to the mild group (p < 0.02). The absolute numbers of CD3+, CD4+, CD8 + T cells, B cells, and NK cells were significantly reduced in the severe group as compared to the mild group (p < 0.05). In patients with severe disease, the proportion of CD8 + and CD4 + T cells were significantly higher than those in patients with mild disease (p = 0.0372). Using ROC analysis, a CD4:8 T cell ratio of ≥ 2.63 and an activated (CD38 + HLA-DR+) CD8 T cell proportion of > 15.85% of the total CD8 T cell population, significantly determined the severe disease category. Conclusions: Severe COVID-19 is associated with severe lymphopenia, altered CD4/CD8 ratio and markedly increased CD8 T cell activation profile. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01558-6.
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Background & objectives: The association between hyperglycaemia at admission, diabetes mellitus (DM) status and mortality in hospitalized SARS-CoV-2 infected patients is not clear. The purpose of this study was to determine the relationship between DM, at-admission hyperglycaemia and 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection requiring intensive care. Methods: All consecutive moderate-to-severe patients with SARS-CoV-2 infection admitted to the intensive care units (ICUs) over six months were enrolled in this single-centre, retrospective study. The predicators for 28 day mortality were analysed from the independent variables including DM status and hyperglycaemia at-admission. Results: Four hundred and fifty two patients with SARS-CoV-2 were admitted to the ICU, with a mean age of 58.5±13.4 yr, 78.5 per cent being male, HbA1c of 7.2 per cent (6.3-8.8) and 63.7 per cent having DM. Overall, 28 day mortality was 48.9 per cent. In univariate analysis, mortality in diabetes patients was comparable with non-diabetes (47.9 vs. 50.6%, P=0.58), while it was significantly higher in hyperglycaemic group (60.4 vs. 35.8%, P<0.001). In multivariate Cox regression analysis, after adjusting for age, sex and comorbidities, hyperglycaemia at-admission was an independent risk factor of mortality [hazard ratio (HR) 1.45, 95% confidence interval (CI) (1.06-1.99), P<0.05]. Interpretation & conclusions: This study showed that the presence of hyperglycaemia at-admission in critically ill SARS-CoV-2 patients was an independent predictor of 28 day mortality. However, the findings may be susceptible to unmeasured confounding, and more research from prospective studies is required.
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COVID-19 , Diabetes Mellitus , Hiperglicemia , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , SARS-CoV-2 , Estudos Retrospectivos , Hiperglicemia/complicações , Unidades de Terapia Intensiva , Diabetes Mellitus/epidemiologiaRESUMO
Background: Our understanding of the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still evolving and is limited for prognostication. The study was performed to predict severity and mortality based on hematology parameters in coronavirus disease (COVID-19). Material and Methods: The study was a single-center retrospective analysis of 240 patients with COVID-19. The hematological parameters were compared between different grades of severity. The receiver operating characteristics (ROC) curve along with the Classification and Regression Trees (CART) methods were used for the analysis. Result: The total leukocyte count, absolute neutrophil count, neutrophil-lymphocyte ratio (NLR), and neutrophil-monocyte ratio (NMR) were increasing along with an increase in severity; while the absolute lymphocyte count and lymphocyte-monocyte ratio (LMR) were decreasing (P < 0.001). For prediction of severity and mortality on admission, the NLR, NMR, and LMR were significant (P < 0.001). The NLR, NMR, and LMR had an area under the receiver operating characteristics curve (AUROC) of 0.86 (95% CI of 0.80-0.91), 0.822 (95% CI of 0.76-0.88), and 0.69 (95% CI of 0.60-0.79), respectively, for severity. While the NLR, NMR, and LMR had an AUROC value of 0.85 (95% CI of 0.79-0.92), 0.83 (95% CI of 0.77-0.89), and 0.67 (95% CI of 0.57-0.78), respectively, for mortality. Conclusion: With the increase in severity there was an increase in the total leukocyte count and absolute neutrophil count while the absolute lymphocyte count decreased. On admission, the cut-off value of NLR >5.2, NMR >12.1, while LMR <2.4 may predict severity and mortality in COVID-19.
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INTRODUCTION: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. METHODS: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. RESULTS: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection. CONCLUSIONS: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. CLINICAL TRIALS REGISTRY: Clinical Trials Registry India (CTRI/2020/07/026668).
The Bacillus CalmetteGuérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine's efficacy as a booster compared with routine COVID-19 vaccine boosters.
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Involvement of the gastrointestinal (GI) system in corona virus disease-19 (COVID-19) in form of diarrhea, loss of taste, nausea, and anorexia is common and associated with poor prognosis. COVID-19 is also associated with a hypercoagulable state that mainly involves the pulmonary vasculature. However, GI complications involving thrombosis are observed infrequently. We report two COVID-19 patients who had two different causes of acute abdomen. The first patient was a 49-year-old male diagnosed with an aortic thrombus along with a splenic infarct. He was diagnosed early and successfully managed with anticoagulants. The second patient was a 30-year-old male who developed pain in the abdomen and was found to have features suggestive of peritonitis. A contrast-enhanced computerized tomography (CECT) scan of the abdomen revealed dilated bowel loops. Immediate exploratory laparotomy was performed; he was found to have jejunal perforation with gangrene. Histopathological examination of the resected specimen showed inflammatory cells with edema and thrombotic vessels. However, he succumbed to sepsis and multiorgan failure. Therefore, it is important to investigate cases of acute abdomen in COVID-19 thoroughly and whenever indicated CT angiogram should be obtained.
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Abdome Agudo , COVID-19 , Trombose , Abdome Agudo/etiologia , Adulto , Anticoagulantes , COVID-19/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Trombose/complicações , Trombose/etiologia , Tomografia Computadorizada por Raios X/métodosRESUMO
Background and objectives The mannoprotein lateral flow assay (MP-LFA) or Aspergillus-specific lateral flow device (AspLFD) is a novel rapid test for point-of-care diagnosis (PoC) of invasive aspergillosis (IA), but its routine clinical application is hampered due to low sensitivity (Sn) of the assay in serum. Therefore, this study aimed to develop a new method to enhance the Sn of the serum MP-LFA. Methodology In the new method (Tripathy method), we used direct heating of the serum without any dilution at 120°C for 15 minutes to purify the mannoprotein (MP) antigen of the Aspergillus. The MP-enriched serum supernatant obtained after centrifugation was loaded in an LFD cassette, and the results were read after 20 minutes using a digital cube reader. In parallel to our new method, AspLFD was performed according to the manufacturer's instructions. The diagnostic performance of the two methods was evaluated using paired sera of true IA patients (IA, n=18) and healthy subjects (controls, n=20). The positivity of the two methods was also evaluated in the sera of leukemia patients with possible/probable IA (possible/probable IA; n=23). Results The Tripathy method had a significantly higher sensitivity (88.9% versus 55.5%; p<0.05) and diagnostic odds ratio (72.0 versus 23.7) than the standard AspLFD method. In receiver operating characteristic curve analysis for differentiation between IA patients and controls, although the Tripathy method (area under curve; AUC: 0.894, p<0.001) and AspLFD method (AUC: 0.753, p<0.001) were significantly associated with IA, the AUC of the Tripathy method was significantly higher than that of the AspLFD method (0.894 versus 0.753; p<0.05). In the sera of possible/probable IA, MP-LFA by the Tripathy method had a significantly higher rate of positivity than the AspLFD method (39.0% versus 21.7%; p<0.05). Conclusion Our data show that the Tripathy method is a highly sensitive method of MP-LFA for the PoC diagnosis of IA in clinical settings.
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BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.