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This case report presents an atypical manifestation of tuberculosis in a 21-year-old male who presented with multiple subcutaneous swellings in the bilateral heel, left elbow, and base of the left third finger for the previous 6 months. The patient also experienced loss of appetite and unintentional weight loss. Despite initial suspicion of bacterial abscesses, antibiotics did not lead to significant improvement. Further investigations revealed an elevated erythrocyte sedimentation rate and findings suggestive of osteomyelitis on imaging. Gene Xpert testing confirmed multidrug-resistant Mycobacterium tuberculosis as the causative agent. The patient was prescribed a bedaquiline-based multidrug-resistant tuberculosis regimen, which resulted in reduction in swelling size. This report highlights the challenges in diagnosing and managing complex cases of primary multiple tubercular abscesses, especially with drug-resistant strains, emphasizing the importance of timely diagnosis and multidisciplinary management for successful outcomes.

Background: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy., Materials and Methods: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA., Results: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy., Conclusions: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Abdominal bloating is a common complaint in patients with functional and organic bowel disease. Rifaximin, a nonabsorbable antibiotic, has been tried for the treatment of this disease. We performed a systematic review and meta-analysis to study the efficacy of rifaximin in abdominal bloating and distension in patients with functional gastrointestinal disorders (FGID)., Methods: We accessed 4 databases (MEDLINE, Embase, SCOPUS, and Web of Science) to identify randomized placebo-controlled trials that utilized rifaximin in FGID. We excluded observational studies, those including patients with organic bowel disorders such as inflammatory bowel diseases, or those in which rifaximin was given for other indications, such as hepatic encephalopathy., Results: A total of 1426 articles were available, of which 813 articles were screened after removing duplicates and 34 articles were selected for full-text review. Finally, 10 trials (3326 patients) were included. Rifaximin was administered in doses ranging from 400 to 1650 mg per day for 1 to 2 weeks. Rifaximin therapy led to a higher likelihood of improvement in symptoms of bloating (44.6% vs. 34.6%, RR 1.22, 95% CI 1.11, 1.35; n=2401 patients) without significant heterogeneity. However, daily doses less than 1200 mg/day were similar to placebo ( P =0.09). Bloating was quantified subjectively in 7 studies, and rifaximin led to a greater reduction in bloating scores compared with placebo (standardized mean difference -0.3, 95% CI -0.51, -0.1, P =0.04) but carried significant heterogeneity ( I2 =61.6%, P =0.01)., Conclusions: Rifaximin therapy is associated with an increased likelihood of improvement in bloating and distension, as well as reduces the subjective severity of these symptoms in patients with FGID., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy., Objective: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study., Patients & Methods: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid., Results: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26)., Interpretation: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Importance: Chronic obstructive pulmonary disease (COPD) is a respiratory condition that is associated with significant health and economic burden worldwide. Previous studies assessed the global current-day prevalence of COPD, but to better facilitate resource planning and intervention development, long-term projections are needed., Objective: To assess the global burden of COPD through 2050, considering COPD risk factors., Design, Setting, and Participants: In this modeling study, historical data on COPD prevalence was extracted from a recent meta-analysis on 2019 global COPD prevalence, and 2010 to 2018 historical prevalence was estimated using random-effects meta-analytical models. COPD risk factor data were obtained from the Global Burden of Disease database., Main Outcomes and Measures: To project global COPD prevalence to 2050, generalized additive models were developed, including smoking prevalence, indoor and outdoor air pollution, and development indices as predictors, and stratified by age, sex, and World Bank region., Results: The models estimated that the number of COPD cases globally among those aged 25 years and older will increase by 23% from 2020 to 2050, approaching 600 million patients with COPD globally by 2050. Growth in the burden of COPD was projected to be the largest among women and in low- and middle-income regions. The number of female cases was projected to increase by 47.1% (vs a 9.4% increase for males), and the number of cases in low- and middle-income regions was expected to be more than double that of high-income regions by 2050., Conclusions and Relevance: In this modeling study of future COPD burden, projections indicated that COPD would continue to affect hundreds of millions of people globally, with disproportionate growth among females and in low-middle income regions through 2050. Further research, prevention, and advocacy are needed to address these issues so that adequate preparation and resource allocation can take place.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The rapid and accurate diagnosis of tubercular lymphadenitis remains a challenging task today. The World Health Organization (WHO) endorsed the LoopAMP MTBC kit (TB-LAMP) as a replacement for sputum smear microscopy in the diagnosis of pulmonary tuberculosis (PTB). However, no prospective diagnostic accuracy study of TB-LAMP for tubercular lymphadenitis in adults has been performed yet. The current study evaluated the diagnostic performance of TB-LAMP in tubercular lymphadenitis (LNTB)., Methods: In a prospective observational study conducted at a tertiary care hospital in India, 90 subjects (age >18 years) suspected of LNTB were recruited consecutively and followed up for 6 months between January 2019 and December 2020. Samples were processed for microscopy, culture, GeneXpert, histopathology and TB-LAMP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TB-LAMP against the composite reference standard (CRS) and culture were determined., Results: TB-LAMP showed a sensitivity of 83.78 % (95 % CI, 73.76-90.47) and a specificity of 81.25 % (95 % CI, 56.99-93.41), respectively, against the CRS. The PPV and NPV were 95.38 % (95 % CI, 87.29-98.42) and 52.00 % (95 % CI, 33.50-69.97), respectively. TB-LAMP showed a sensitivity of 88.89 % (95 % CI, 71.94-96.15) and a specificity of 36.17 % (95 % CI, 23.97-50.46), respectively, against culture. The PPV and NPV were 44.44 % (95 % CI, 32-57.62) and 85 % (95 % CI, 63.96-94.76), respectively., Conclusion: TB-LAMP can be used instead of conventional microscopy for the diagnosis of TB in lymph node specimens at primary healthcare centres. It provides rapid and cost-effective diagnosis of LNTB in resource-limited settings due to good sensitivity and NPV., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Context: Gas discharge visualization (GDV) works on the principle of the Kirlian effect. It's a noninvasive, quick, and safe biometric tool to investigate the psychophysiological state of an individual, with the potential to identify deviations from the healthy functioning of humans at early stages., Objective: The study intended to systematically document the scientific evidence pertaining to the use of GDV devices in human health and disease conditions., Design: The research team performed a systematic search for studies on GDV on research databases such as Google Scholar, PubMed, and PsychINFO, using the following inclusion criteria: (1) experimental studies dealing with a GDV device, (2) studies dealing with human participants related to health and disease, and (3) studies published in the English language. The study excluded: (1) review articles, (2) case studies, (3) letter to editors, (4) studies with unclear methodology, and (5) studies published before the year 2000., Setting: The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bengaluru, India., Results: After filtering, the research team obtained 108 publications that dealt with the application of a GDV device in human participants. Based on the selection criteria, 42 studies were included in the review. These 42 studies included eight randomized controlled trials (RCTs), five nonrandomized controlled studies, 17 cross-sectional studies, 10 single-group pre-post studies, and two correlational studies., Conclusions: More studies with a robust methodology are needed to make definitive conclusions. The literature reveals that the GDV technique has the potential to provide early diagnosis and screening, especially in disorders of the endocrine and immune systems. It might also be used to assess wellness in healthy subjects and monitor the effects of interventions, such as yoga-including pranayama and meditation, acupuncture, qigong, music therapy, and massage on the human energy system. Future studies should focus on the validation of GDV imaging in clinical settings.

Introduction: In resource-limited settings, obstructive sleep apnea (OSA) often goes undiagnosed as polysomnography (PSG) is expensive, time-consuming, and not readily available. Imaging studies of upper airway have been tried as alternatives to PSG to screen for OSA. However, racial differences in upper airway anatomy preclude generalizability of such studies. We sought to test the hypothesis that ultrasonography (USG), an inexpensive, readily available tool to study soft tissue structures of the upper airway, would have predictive value for OSA in South Asian people., Methods: Adult patients with sleep-related complaints suspicious for OSA were taken for overnight PSG. After the PSG, consecutive patients with and without OSA were studied with submental ultrasonography to measure tongue base thickness (TBT) and lateral pharyngeal wall thickness (LPWT)., Results: Among 50 patients with OSA and 25 controls, mean age was 43.9 ± 11.4 years, and 39 were men. Patients with OSA had higher TBT (6.77 ± 0.63 cm vs 6.34 ± 0.54 cm, P value = 0.004) and higher LPWT (2.47 ± 0.60 cm vs 2.12 ± 0.26 cm, P value = 0.006) compared to patients without OSA. On multivariate analysis, TBT, LPWT, and neck circumference were identified as independent factors associated with OSA. These variables could identify patients with severe OSA with a sensitivity of 72% and a specificity of 76%., Conclusion: Patients with OSA have higher tongue base thickness and lateral pharyngeal wall thickness proportionate to the severity of the disease, independent of BMI and neck circumference. These findings suggest that sub-mental ultrasonography may be useful to identify patients with severe OSA in resource-limited settings., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Patients on central lines are often having multiple morbidities, and invasive devices provide a niche for biofilm formation, which makes central line-associated bloodstream infections (CLABSIs), a serious concern in health-care settings, as the infections difficult to treat. In this study, we evaluated the common bacteria causing CLABSI, and various patient and pathogen factors affecting the clinical outcome., Methods: In the prospective observational study, patients diagnosed with CLABSI were recruited. Extensive clinical, microbiological, and other laboratory workup was done, and observations were recorded. Congo red agar method, tube test, and microtiter plate assay were used for eliciting the biofilm-forming attributes of the bacterial pathogens., Results: Klebsiella pneumoniae was responsible for 48% of CLABSI, followed by Coagulase-negative Staphylococci (16%) and Staphylococcus aureus and Acinetobacter baumannii (12% each). Fifty-six percent of the isolates produced biofilms. The median (interquartile range) duration of hospital stay till death or discharge was 30 (20, 43) days. The all-cause mortality was 44%. Patients having a deranged liver function on the day of diagnosis ( P value for total bilirubin 0.001 and for aspartate transaminase 0.02), and those infected with multidrug-resistant organisms ( P value = 0.04) had significantly poor prognosis. The difference in the demographic, clinical, laboratory profile, and outcome of patients infected with biofilm producers and nonproducers was not found to be statistically significant., Conclusion: The study throws light on various host and pathogen factors determining the cause and outcome of CLABSI patients. To the best of our knowledge, this is the first study trying to decipher the role of biofilm formation in the virulence of pathogens and the prognosis of CLABSI., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Global Infectious Diseases.)

RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees. STING agonists (cAIMP, diABZI, and 2',3'-cGAMP) and Dectin-1 agonist scleroglucan demonstrate the most potent, broad-spectrum antiviral function. Furthermore, STING agonists inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals that cAIMP treatment rescue cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provides protection against CHIKV in a chronic CHIKV-arthritis mouse model. Our study describes innate immune signaling circuits crucial for RNA virus replication and identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse., Methods: This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture., Results: A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups., Conclusions: The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion., Trial Registration: CTRI/2021/02/030977 (ICMR, Clinical trial registry-India)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sinha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: It has been more than 17 years since the introduction of free ART in India. At this point, it would be prudent to look at the factors associated with the survival of persons living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLHA) who are already enrolled in the ART program., Methods: PLHAs enrolled from antiretroviral therapy (ART) centers located in three different cities in India - Delhi, Pune and Kolkata, and were followed up at six monthly intervals monitoring the WHO stage, CD4 counts, complete blood counts, and liver and kidney function tests, for a duration of three years., Results and Discussion: The incidence of mortality among HIV/AIDS patients on ART was 5.0 per 1000 patient-years (21/1410, 1.4%). Age at initiation of ART, being above 35 years, was the only significant predictor of mortality (log-rank p = 0.018). Multivariable analysis showed a significant association of an unfavourable outcome (defined as mortality or development of opportunistic infection during follow-up) with male gender (adjusted odds ratio (AOR) = 5.26, p = <0.01) and being unmarried at ART initiation (AOR = 1.39, p = 0.005)., Conclusion: The survival of PLHA with good adherence to ART is independent of the WHO stage or CD4 counts at the initiation of ART. Initiation of ART after 35 years of age was a significant predictor of mortality., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction:  Fracture or surgical intervention of fracture of the shaft of the humerus may cause injury to the nutrient artery leading to the nonunion or delayed union of the fracture. It is important to find the number and location of the nutrient artery. So the knowledge regarding the nutrient foramen helps to protect them during any operative procedure of the shaft of the humerus. The main objective of this study is to find out the number, location, and direction of the nutrient foramen of the humerus., Materials and Methods: The study was conducted on 80 dried humeri of unknown gender obtained from Narayan Medical College, Sasaram, Bihar, India, and also from other medical colleges of Bihar. The number, location, and direction of nutrient foramen were observed., Results: The majority of humeri showed one nutrient foramen, which was found in 91.25%, followed by 3.75% with double foramen and 1.25% with triple foramen. Nutrient foramen was absent in 3.75% of the humerus. The majority (89.02%) of nutrient foramen was found on the anteromedial surface followed by anterolateral (9.76%) and posterior surface (1.22%). The majority of nutrient foramen was found on the middle third (86.58%) of the shaft, followed by 13.42% on the distal third. No nutrient foramen was found on the proximal third of the humerus. All nutrient foramina were directed downward., Conclusion: The location of the nutrient foramen of the humerus was not constant; it may present on anteromedial, anterolateral, or posterior surfaces. Similarly, it may present on the middle or distal third of the shaft of the humerus. This study will help surgeons planning the surgical intervention of the shaft of the humerus, which will possibly reduce the chances of nonunion or delayed union., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kumar et al.)

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)., (© 2022. The Author(s).)

New variants of SARS-CoV-2 continue to evolve. The novel SARS-CoV-2 variant of concern (VOC) B.1.1.529 (Omicron) was particularly menacing due to the presence of numerous consequential mutations. In this study, we reviewed about 12 million SARS-CoV-2 genomic and associated metadata using extensive bioinformatic approaches to understand how evolutionary and mutational changes affect Omicron variant properties. Subsampled global data based analysis of molecular clock in the phylogenetic tree showed 29.56 substitutions per year as the evolutionary rate of five VOCs. We observed extensive mutational changes in the spike structural protein of the Omicron variant. A total of 20% of 7230 amino acid and structural changes exclusive to Omicron's spike protein were detected in the receptor binding domain (RBD), suggesting differential selection pressures exerted during evolution. Analyzing key drug targets revealed mutation-derived differential binding affinities between Delta and Omicron variants. Nine single-RBD substitutions were detected within the binding site of approved therapeutic monoclonal antibodies. T-cell epitope prediction revealed eight immunologically important functional hotspots in three conserved non-structural proteins. A universal vaccine based on these regions may likely protect against all these SARS-CoV-2 variants. We observed key structural changes in the spike protein, which decreased binding affinities, indicating that these changes may help the virus escape host cellular immunity. These findings emphasize the need for continuous genomic surveillance of SARS-CoV-2 to better understand how novel mutations may impact viral spread and disease outcome.

Background: During flexible fibreoptic bronchoscopy through the nasal route, anaesthesia of the nasal passage is achieved by lignocaine gel application by a slip-tip syringe or with the help of a cotton tip swab. No studies in existing literature have compared the two techniques in terms of efficacy., Methods: 137 consecutive patients undergoing bronchoalveolar lavage (BAL) were recruited over a 2-year period. The patients underwent BAL after nasal anaesthesia-either by slip-tip syringe or by cotton tip swab smeared with 2% lignocaine gel. Patients were monitored for intraprocedural epistaxis, discomfort and improvement in operator visibility of nasal passage., Results: 67 patients were randomised to cotton swab and 70 patients to the gel instillation group. There were no significant differences in terms of epistaxis, 29.9% in the cotton tip swab (95% CI 19.3% to 42.3%) versus 24.3% in the gel instillation group (95% CI 14.8% to 36%) or detection of nasal blocks, 7.5% in the cotton tip swab (95% CI 2.5% to 16.6%) versus 10% in the gel instillation group (95% CI 4.1% to 19.5%) in the two groups, although a significant difference was there in terms of visibility, 73.1% in the cotton tip swab (95% CI 60.9% to 83.2%) versus 42.9% in the gel instillation group (95% CI 31.1% to 55.3%). There was no difference in the mean pain score across the two groups either during the procedure or 1 hour after it. A short systematic review of existing literature on the topic has been provided for comparison., Conclusion: Application of 2% lignocaine gel by slip-tip syringe and cotton tip swab are equivalent in terms of observed and narrated pain experienced by patients, frequency of epistaxis and nasal blocks. Vision was better preserved in the cotton tip swab group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Literature is lacking on the spectrum of symptoms of long COVID-19 (defined as symptoms persisting beyond 28 days of diagnosis) and its impact on quality of life. This single-center, cross-sectional study included mild COVID-19 cases as determined by a positive real-time reverse transcription polymerase chain reaction test. Patients were contacted at least 28 days after diagnosis and were interviewed telephonically using semi-structured questionnaires for duration of symptoms, fatigue using Fatigue Severity Scale (FSS) and quality of life using the World Health Organization Quality of Life: Brief Version (WHOQOL-BREF). A total of 251 COVID-19 patients were included; of which 169 (67.3%) were males. The mean age of the patients was 35.8 years (SD = 12.5). The prevalence of long COVID-19 was 28.2% (n = 71, 95% CI: 23.0-34.2). The most common symptoms involved the musculoskeletal system (12.7%), upper respiratory tract (7.6%), and fatigue among 17 (6.8%) patients. Patients with long COVID-19 had significantly higher FSS score and lower WHOQOL-BREF score compared to the patients without long COVID-19 (<28 days)., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Competing Interests: There are no conflicts of interest.

HIV stigma takes a multidimensional toll on a mother's ability to care for herself and subsequently may impact her ability to care for her child, particularly when mother and child are seroconcordant. A cross-sectional analysis was conducted to examine the association between maternal HIV stigma and child CD4 count in rural India. We assessed 108 mother-child dyads and found that a one-unit increase in community stigma fear decreased child CD4 count by 352 cells (95% CI = - 603, - 102), highlighting the need to develop a better understanding of the consequences of HIV-related stigma on the compounded burden of care in households where mother and child both live with HIV., (© 2021. The Author(s).)

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis with underlying circulatory cellular and metabolic abnormalities associated with higher mortality rates. However, a detailed understanding of sepsis is still limited. The present study reports the differences in the metabolic profile of serum samples of patients with sepsis compared to healthy controls using Nuclear Magnetic Resonance (NMR) spectroscopy. The study also compares the NMR metabolomics on day zero of admission among sepsis survivors (those who survived till day seven) and sepsis non-survivors (those who succumbed on day zero). Furthermore, the different metabolites in serum were analysed by univariate and multivariate analysis, ROC analysis, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. Metabolites with VIP score (>1·0) were considered as potential biomarker/s to discriminate sepsis survivors from non- survivors at day zero. Data showed that phenylalanine was significantly higher in sepsis patients compared to healthy controls, whereas isoleucine, valine and histidine were significantly lower in sepsis patients compared to healthy controls. Also, non-survivors had higher serum levels of creatine, phosphocreatine, choline, betaine, tyrosine, histidine and phenylalanine concentrations than survivors. These findings suggest that the metabolic alterations at day zero may predict the survival of patients with sepsis. The significant differences seen in metabolites concentration of amino acids, phospholipids and creatine may be used as early prognostic markers to discriminate non-survivors from survivors of sepsis patients at day zero. Our findings indicate that the metabolite alterations are associated with the progression of the disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The objective of this subanalysis of data from centres across urban areas in India of the Global Asthma Network (GAN) was to study 1) the prevalence of symptoms of asthma in children and adults, 2) the change in prevalence of asthma and its trigger factors since the International Study of Asthma and Allergies in Childhood (ISAAC), and 3) current asthma treatment practice., Methods: In this cross-sectional, multicentre, school-based and self-administered questionnaire, responses from children aged 6-7 years and 13-14 years, and their respective parents, were analysed., Results: The GAN Phase I study included 20 084 children in the 6-7-year age group, 25 887 children in the 13-14-year age group and 81 296 parents. The prevalence of wheeze in the previous 12 months was 3.16%, 3.63% and 3.30% in the three groups, respectively. In comparison to the ISAAC studies, there was a significant reduction in the prevalence of current wheeze (p<0.001). Bivariate analysis revealed a significant reduction in the prevalence of trigger factors. Almost 82% of current wheezers and 70% of subjects with symptoms of severe asthma were not clinically diagnosed as having asthma. The daily use of inhaled corticosteroids (ICS) was less than 2.5% in subjects with current wheeze and those with symptoms of severe asthma but less than 1% used daily ICS when asthma remained undiagnosed., Conclusion: The prevalence of current wheeze and its causal factors showed a significant reduction compared to previous ISAAC studies. Among subjects with current wheeze and symptoms of severe asthma, the problem of under-diagnosis and under-treatment was widespread., Competing Interests: Conflict of interest: There is no conflict of interest to report by any of the authors., (Copyright ©The authors 2022.)

A patient, an adolescent male, presented to us with complaints of recurrent respiratory tract infections since childhood. Differentials considered were cystic fibrosis (CF), bronchial asthma with allergic bronchopulmonary aspergillosis (ABPA), primary ciliary dyskinesia (PCD) and primary immunodeficiency disorders. Sweat chloride test, total IgE and Aspergillus fumigatus specific serum IgE and IgG levels were normal ruling out CF and ABPA. Nasal nitric oxide (NO) screening test showed reduced NO levels, and high-speed video microscopy of nasal scrapings showed stiff beating cilia with reduced ciliary beat frequency confirming the diagnosis of PCD. Immunodeficiency workup showed reduced serum IgG, IgA and IgM, when repeated on two separate occasions when the patient was not harbouring any active infection, suggestive of pan-hypogammaglobulinaemia. Thus, a diagnosis of coexistent PCD and pan-hypogammaglobulinaemia was made. Detection of immunodeficiency disorders is important in patients with PCD as they may benefit from immunoglobulin replacement., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Tuberculosis (TB) remains a significant global health crisis and the number one cause of death for an infectious disease. The health consequences in high-burden countries are significant. Barriers to TB control and eradication are in part caused by difficulties in diagnosis. Improvements in diagnosis are required for organisations like the World Health Organisation (WHO) to meet their ambitious target of reducing the incidence of TB by 50% by the year 2025, which has become hard to reach due to the COVID-19 pandemic. Development of new tests for TB are key priorities of the WHO, as defined in their 2014 report for target product profiles (TPPs). Rapid triage and biomarker-based confirmatory tests would greatly enhance the diagnostic capability for identifying and diagnosing TB-infected individuals. Protein-based test methods e.g. lateral flow devices (LFDs) have a significant advantage over other technologies with regard to assay turnaround time (minutes as opposed to hours) field-ability, ease of use by relatively untrained staff and without the need for supporting laboratory infrastructure. Here we evaluate the diagnostic performance of nine biomarkers from our previously published biomarker qPCR validation study; CALCOCO2, CD274, CD52, GBP1, IFIT3, IFITM3, SAMD9L, SNX10 and TMEM49, as protein targets assayed by ELISA. This preliminary evaluation study was conducted to quantify the level of biomarker protein expression across latent, extra-pulmonary or pulmonary TB groups and negative controls, collected across the UK and India, in whole lysed blood samples (WLB). We also investigated associative correlations between the biomarkers and assessed their suitability for ongoing diagnostic test development, using receiver operating characteristic/area under the curve (ROC) analyses, singly and in panel combinations. The top performing single biomarkers for pulmonary TB versus controls were CALCOCO2, SAMD9L, GBP1, IFITM3, IFIT3 and SNX10. TMEM49 was also significantly differentially expressed but downregulated in TB groups. CD52 expression was not highly differentially expressed across most of the groups but may provide additional patient stratification information and some limited use for incipient latent TB infection. These show therefore great potential for diagnostic test development either in minimal configuration panels for rapid triage or more complex formulations to capture the diversity of disease presentations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garlant, Ellappan, Hewitt, Perumal, Pekeleke, Wand, Southern, Kumar, Belgode, Abubakar, Sinha, Vasan, Joseph and Kempsell.)

Background: The diagnosis of CPA relies on the detection of the IgG Aspergillus antibody, which is not freely available, especially in resource-poor settings. Point-of-care tests like LDBio Aspergillus ICT lateral flow assay, evaluated in only a few studies, have shown promising results for the diagnosis of CPA. However, no study has compared the diagnostic performances of LDBio LFA in setting of tuberculosis endemic countries and have compared it with that of IgG Aspergillus. Objectives: This study aimed to evaluate the diagnostic performances of LDBio LFA in CPA and compare it with existing the diagnostic algorithm utilising ImmunoCAP IgG Aspergillus. Methods: Serial patients presenting with respiratory symptoms (cough, haemoptysis, fever, etc.) for >4 weeks were screened for eligibility. Relevant investigations, including direct microscopy and culture of respiratory secretions, IgG Aspergillus, chest imaging, etc., were done according to existing algorithm. Serums of all patients were tested by LDBio LFA and IgG Aspergillus (ImmunoCAP Asp IgG) and their diagnostic performances were compared. Results: A total of 174 patients were included in the study with ~66.7% patients having past history of tuberculosis. A diagnosis of CPA was made in 74 (42.5%) of patients. The estimated sensitivity and specificity of LDBio LFA was 67.6% (95% CI: 55.7−78%) and 81% (95% CI: 71.9−88.2%), respectively, which increased to 73.3% (95% CI: 60.3−83.9%) and 83.9% (95% CI: 71.7−92.4%), respectively, in patients with a past history of tuberculosis. The sensitivity and specificity of IgG Aspergillus was 82.4% (95% CI: 71.8−90.3%) and 82% (95% CI: 73.1−89%); 86.7% (95% CI: 75.4−94.1%) and 80.4% (95% CI: 67.6−89.8%), in the whole group and those with past history of tuberculosis, respectively. Conclusions: LDBio LFA is a point-of-care test with reasonable sensitivity and specificity. However, further tests may have to be done to rule-in or rule-out the diagnosis of CPA in the appropriate setting.

Background: The Global Asthma Network phase I study in India aimed to study the prevalence, time trends, and associated risk factors of allergic rhinitis and eczema among 6-7-year-old, and 13-14-year-old school children and their parents. Objectives:  The objective of the study was to understand the current prevalence and associated risk factors of Allergic Rhinitis and Eczema in India among 6-7-year-olds, 13-14-year-olds and in their parents/guardians for newer directions to health care providers, policy makers and academicians., Methods: Cross-sectional, multicenter study using self- and parent-administered questionnaire among randomly selected school children aged 6 to 7 years from 8 centers and 13 to 14 years from 9 centers and their respective parents/guardians across India., Results: Prevalence of allergic rhinitis (AR) (%, 95% CI) among 20,084 6-7-year-olds (children), 25,887 13-14-year-olds (adolescents), and 81,296 adults/parents was 7.7% (7.4%-8.1%), 23.5% (23.0%-24.1%), and 9.8% (9.55%-9.96%) and that of eczema was 2.5% (2.3%-2.7%), 3.5% (3.27%-3.71%), and 9.9% (9.7%-10.1%), respectively. Among 6-7-year-olds, AR and eczema showed a significantly ( P  < .001) declining time trend since the International Study of Asthma and Allergies in school children phase III in 2002-2003. Among 13-14-year-olds, AR ( P  < .01) but not eczema showed a significant temporal decline. Coexisting atopic condition, parental history of atopy, and some environmental factors consistent with previous studies were significant risk factors among children and adolescents. AR or eczema in either parent strongly predicted the same atopic condition among their adolescent offspring. Among adults, coexisting atopic condition was the strongest predictor of either AR or eczema., Conclusions: There is a slight declining time trend of AR and eczema in India over 2 decades among children and adolescents. Nearly 10% of Indian adults suffer from AR and eczema. Although genetic factors had the strongest association for AR and eczema among all age groups, certain early-life and environmental exposures need consideration to devise preventative strategies., (© 2022 The Authors.)

Background: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection., Methods: We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%., Findings: Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61)., Interpretation: This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures., Funding: None., Translation: For the Hindi translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies., Methods: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors., Results: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM., Conclusion: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective was to study the sensitivity, specificity, and diagnostic accuracy of various computed tomography (CT) chest findings in diagnosing recurrence among pulmonary tuberculosis (PTB) suspects., Materials and Methods: A prospective observational study was conducted in a tertiary care hospital in New Delhi. A total of 130 suspects with a past history of treatment for PTB, who presented with any of the symptoms suggestive of recurrence were included. Sputum-positive, HIV-positive patients, pregnant females, and patients aged <18 years were excluded. Patients underwent CT chest followed by bronchoalveolar lavage (BAL)., Results: A total of 62 patients were there in the final analysis. The median age of the patients with recurrent PTB was 27.5 years. Cough was the universal symptom in all these patients (>90%). Hemoptysis was the predominant symptom among patients with chronic pulmonary aspergillosis (66.6%). Necrotic mediastinal lymph nodes had good diagnostic accuracy of 88.71% with area under the curve of 0.806, P < 0.001 in diagnosing recurrent TB. BAL GeneXpert and mycobacteria growth indicator tube had good sensitivity (83.33% and 84.62%, respectively), specificity (100% for both), and excellent diagnostic accuracy (95.16% and 96.36%, respectively) for diagnosing recurrence in sputum negative and sputum scarce patient, (P < 0.001) when compared with composite reference standard. For culture-positive cases, BAL GeneXpert MTB/RIF had 100% sensitivity and 97.73% specificity in diagnosing recurrent PTB patients., Conclusion: The presence of mediastinal necrotic lymph node is the most accurate CT finding that can differentiate recurrent TB from post-TB sequelae. No other single chest CT scan finding had reliable diagnostic accuracy in comparison to microbiological tools in diagnosing recurrence among sputum negative or scarce previously treated PTB suspects., Competing Interests: None

Background & Objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population., Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants., Results: Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively., Interpretation & Conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study.

Background: Though invasive pulmonary aspergillosis is a well known complication of COVID-19 pneumonia, indolent forms of aspergillosis have been rarely described., Methods: We prospectively collected the clinico-radio-microbiological data of 10 patients of subacute invasive pulmonary aspergillosis (SAIA), who presented to our hospital with recent history of COVID-19 pneumonia along with cavitary lung disease, positive IgG (against Aspergillus) with or without positive respiratory samples for Aspergillus spp., Result: The mean age of presentation of SAIA was 50.7 ± 11.8 years. All the patients had recently recovered from severe COVID-19 illness with a mean duration of 29.2 ± 12 days from COVID-19 positivity. Cough was the predominant symptom seen in 8/10 (80%) patients followed by haemoptysis. 7/10 (70%) patients were known diabetic. While serum galactomannan was positive in 5/9 patients (55.5%), fungal culture was positive in 2/7 patients (28.5%) and polymerase chain reaction (PCR) for Aspergillus was positive in three patients. Eight (80%) patients presented with a single cavitary lesion; pseudoaneurysm of pulmonary artery was seen in two patients and post-COVID-19 changes were seen in all patients. All patients were treated with voriconazole, out of which four (40%) patients died during the follow-up period., Conclusion: SAIA should be considered in the differential diagnosis of cavitating lung lesions in patients with recent history of COVID-19 in the background of steroid use with or without pre-existing diabetes., (© 2021 Wiley-VCH GmbH.)

Loss of lean muscle mass impairs immunity and increases mortality risk among individuals with HIV/AIDS. We evaluated the relative contributions of protein supplementation and nutrition education on body composition among 600 women living with HIV/AIDS in rural Andhra Pradesh, India. We conducted a cluster randomized controlled 2 × 2 factorial trial lasting six months with follow up at twelve and eighteen months. Interventions occurred in the Nellore and Prakasam regions of Andhra Pradesh by trained village women, ASHA (Accredited Social Health Activists), and included: (1) the usual supportive care from ASHA (UC); (2) UC plus nutrition education (NE); (3) UC plus nutritional protein supplementation (NS); (4) combined UC plus NE plus NS. A Bioimpedance Analyzer Model 310e measured body composition. SAS 9.4 analyzed all data. Mixed models using repeated measures evaluated lean mass change from baseline as primary and fat weight and total weight as secondary outcomes. Lean mass change was significantly associated with NS ( p = 0.0001), NE ( p = 0.0001), and combined NS plus NE ( p = 0.0001), with similar associations for secondary outcomes. Stronger associations for total weight were observed with greater ART adherence. Nutritional interventions may improve physiologic response to HIV. Significant increases in lean mass resulted from independent and combined protein supplementation and nutrition education.

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO 2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.

Background and Aims: This meta-analysis aims to highlight the impact of cardio-metabolic comorbidities on COVID-19 severity and mortality., Methods: A thorough search on major online databases was done for studies describing the clinical outcomes of COVID-19 patients. We used random-effects model to compute pooled estimates for critical or fatal disease., Results: A total of 20,475 patients from 33 eligible studies were included. Maximum risk of development of critical or fatal COVID-19 disease was seen in patients with underlying cardiovascular disease [OR: 3.44, 95% CI: 2.65-4.48] followed by chronic lung disease, hypertension and diabetes mellitus. Of the total cases, 64% had one of the four comorbidities with the most prevalent being hypertension with a pooled prevalence of 27%., Conclusions: Presence of comorbidities like cardiovascular disease, chronic lung disease, hypertension and diabetes mellitus led to a higher risk of development of critical or fatal COVID-19 disease, with maximum risk seen with underlying cardiovascular disease., Competing Interests: Declaration of competing interest The authors report no conflict of interest relevant to the published work., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Pulmonary aspergilloma (PA) is a common complication seen in patients with pulmonary tuberculosis sequelae. Antifungal therapy, including oral azoles, is commonly used though only surgical resection offers curative benefit. Local administration of amphotericin B, like intracavitary instillation, has been effective in aspergilloma patients though nebulised amphotericin B (nAB) has never been formally assessed., Objective: The aim of this prospective, non-inferior, open-label, randomised control trial is to evaluate the efficacy and safety of nebulised amphotericin B compared to oral itraconazole therapy in the treatment of PA., Patients/methods: Diagnosed cases of PA (n=33) were randomised into the control group receiving oral itraconazole (n=18) and intervention group receiving nebulised amphotericin B (n = 15). Response to treatment was assessed both clinically and radiologically at the end 6 months., Results and Conclusion: The number of patients showing overall improvement at the end of 6 months in the control arm(oral itraconazole) vs intervention arm(nebulised amphotericin B) was 65% (95% CI 38.3-85.8) and 67%(95% CI 38.4%-88.2%), respectively, in the intention-to-treat and 79% (95% CI 49.2%-95.3%), and 65% (95% CI 38.4%-88.2%), respectively, in the per-protocol analysis. While there was no statistically significant difference between the intervention and control arm in both the analyses, non-inferiority was shown in the per-protocol but not in the intention-to-treat analysis. No major adverse events were noted in either group; however, a significant proportion of patients receiving nAB reported minor cough (40%), which, however, did not lead to discontinuation of therapy in any patients. Nebulised amphotericin B can be an effective therapeutic option for pulmonary aspergilloma patients., (© 2021 Wiley-VCH GmbH.)

Background: Currently, there is no data on the impact of COVID-19 on patients' income and work in India., Methods: We conducted a cross-sectional study at a tertiary hospital in New Delhi. We included all the patients who were ≥18 years of age and consecutively diagnosed with COVID-19 between the 1 st of May 2020 to 31 st July 2020. Patients were interviewed by a physician using a semi-structure questionnaire. Data were collected on socio-economic status, occupation, income loss, leaves taken, decrease in work efficiency (self-perceived) and about-facing any stigma/discrimination at the workplace., Results: Out of 245 patients, 190 patients were employed. A total of 126 patients (66.3%) self-reported their work was affected due to COVID-19 disease. A total of 30.5% of patients ( n = 58/190) reported deduction in their salary. The median amount of salary loss was INR 10,000 (IQR 9000-25000). Decrease in income and work efficiency (self-perceived) was found to be 37.3% ( n = 71) and 12.1% ( n = 23), respectively. A total of 47 patients (37.3%) took personal leaves (median number - 17 days (IQR 14-25), and discrimination/stigma related to the COVID-19 at the workplace was faced by 22.6% of patients., Conclusion: Income and work of a substantial number of patients was affected due to COVID-19, as there was a decrease in income and work efficiency. Patients also had to take personal leaves and face stigma in the workplace. This will inform the policymakers to formulate strategies to mitigate the impact of COVID-19., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Family Medicine and Primary Care.)

Background: The emergence of drug-resistant tuberculosis (TB), is a major menace to cast off TB worldwide. Line probe assay (LPA; GenoType MTBDRplus ver. 2) and Xpert MTB/RIF assays are two rapid molecular TB detection/diagnostic tests. To compare the performance of LPA and Xpert MTB/RIF assay for early diagnosis of rifampicin-resistant (RR) TB in acid-fast bacillus (AFB) smear-positive and negative sputum samples., Methods: A total 576 presumptive AFB patients were selected and subjected to AFB microscopy, Xpert MTB/RIF assay and recent version of LPA (GenoType MTBDRplus assay version 2) tests directly on sputum samples. Results were compared with phenotypic culture and drug susceptibility testing (DST). DNA sequencing was performed with rpoB gene for samples with discordant rifampicin susceptibility results., Results: Among culture-positive samples, Xpert MTB/RIF assay detected Mycobacterium tuberculosis (Mtb) in 97.3% (364/374) of AFB smear-positive samples and 76.5% (13/17) among smear-negative samples, and the corresponding values for LPA test (valid results with Mtb control band) were 97.9% (366/374) and 58.8% (10/17), respectively. For detection of RR among Mtb positive molecular results, the sensitivity of Xpert MTB/RIF assay and LPA (after resolving discordant phenotypic DST results with DNA sequencing) were found to be 96% and 99%, respectively. Whereas, specificity of both test for detecting RR were found to be 99%., Conclusion: We conclude that although Xpert MTB/RIF assay is comparatively superior to LPA in detecting Mtb among AFB smear-negative pulmonary TB. However, both tests are equally efficient in early diagnosis of AFB smear-positive presumptive RR-TB patients.

Background & Objectives: Despite advances in diagnostics and therapeutics, tuberculosis (TB) is widely prevalent and contributes to a significant burden of illness in both developing and developed nations. The present study was aimed to assess the role of coronin in TB patients and healthy controls. Coronin is a leucocyte-specific protein that is actively recruited in mycobacterial phagolysosomes, where it inhibits lysosomal delivery of Mycobacterium by activating a calcium-dependent phosphatase-calcineurin., Methods: In the study, 100 newly diagnosed cases of TB (pulmonary and extra-pulmonary) and healthy controls were prospectively enrolled over one year and the levels of coronin-1a in these patients and controls were measured by quantitative PCR (qPCR)., Results: A total of 100 TB patients and 100 healthy individuals as controls were assessed. There were 59 patients with extra-pulmonary TB (EPTB) and 41 of pulmonary TB (PTB). In 47 per cent of patients, corroborative histopathological evidence of TB was also available. Significantly higher values of coronin-1a were observed in TB patients (19.94±2.61) than in healthy controls (16.09±1.91) (P<0.001)., Interpretation & Conclusions: Coronin 1a appears to play an important role in the TB disease pathophysiology and agents developed against coronin may have a role in the treatment of TB. Further studies are required to assess if coronin-1a levels are elevated in non-tubercular infective a etiologies and whether these can be a potential drug target in patients with TB.

Background & Objectives: In the present scenario, the most common sample for diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) is nasal and throat swab (NTS). Other sampling options such as gargle lavage have found limited application in clinical use mostly because of unavailability of an appropriate gargling liquid. This study was conducted to assess the stability of SARS-CoV-2 RNA in normal saline at 4°C that can serve as a gargling liquid as well as a transport medium. The study also looked at the agreement between NTS and gargle lavage/saliva for the detection of SARS-CoV-2., Methods: In 29 consecutive real-time RT-PCR (rRT-PCR) positive COVID-19 patients, paired NTS, gargle and saliva samples were taken. Samples were processed by rRT-PCR for the detection of SARS-CoV-2 RNA. To assess the SARS-CoV-2 RNA stability in normal saline, gargle lavage specimens were divided into two aliquots; one subset of the specimen was run within 4-6 h along with the routine samples (NTS and saliva) and the other subset was stored at 4°C and processed after 24-30 h. Agreement between cycle threshold (Ct) values from both the runs was compared using Bland-Altman (BA) analysis., Results: The positivity rates of rRT-PCR in NTS, saliva and gargle lavage samples were 82.7 (24/29), 79.3 (23/29) and 86.2 per cent (25/29), respectively. BA plot showed a good agreement between the Ct values of fresh and stored gargle samples, stipulating that there were no significant differences in the approximate viral load levels between the fresh and stored gargle lavage samples (bias: E gene -0.64, N gene -0.51, ORF gene -0.19)., Interpretation & Conclusions: Our study results show stability of SARS-CoV-2 RNA in the gargle samples collected using normal saline up to 24-30 h. Gargle lavage and saliva specimen collection are cost-effective and acceptable methods of sampling for the detection of SARS-CoV-2 RNA by rRT-PCR. These simplified, inexpensive and acceptable methods of specimen collection would reduce the cost and workload on healthcare workers for sample collection., Competing Interests: None

Introduction : The COVID-19 pandemic has provided global challenges to health-care facilities in ensuring the delivery of care to patients. Tremendous international collaboration has enabled the swift formulation of evidence-based guidelines that aim to clarify day-to-day issues faced by physicians and other health-care providers on the frontlines. Areas covered : In order to provide answers to the common questions and dilemmas faced by physicians and policymakers, especially those handling pulmonary manifestations of COVID-19, the authors made a list of pertinent clinical topics that were reviewed between 21st of August, 2020 to 30th of August, 2020 by the authors using online databases that included PubMed, EBSCO, and the Cochrane Library. Literature was reviewed and included based on relevance to the topics selected. The review was aimed to serve as a quick reference for addressing practical issues faced during patient care in the ongoing pandemic with a brief account of the management of COVID-19 patients as per international guidelines. Expert opinion : As more evidence continues to generate regarding the optimal methods of managing COVID-19 cases while caring for non-COVID patients concurrently, physicians will need to constantly reeducate themselves to keep pace with a rapidly evolving landscape of therapeutic options.

Tuberculosis (TB) remains a major global threat and diagnosis of active TB ((ATB) both extra-pulmonary (EPTB), pulmonary (PTB)) and latent TB (LTBI) infection remains challenging, particularly in high-burden countries which still rely heavily on conventional methods. Although molecular diagnostic methods are available, e.g., Cepheid GeneXpert, they are not universally available in all high TB burden countries. There is intense focus on immune biomarkers for use in TB diagnosis, which could provide alternative low-cost, rapid diagnostic solutions. In our previous gene expression studies, we identified peripheral blood leukocyte (PBL) mRNA biomarkers in a non-human primate TB aerosol-challenge model. Here, we describe a study to further validate select mRNA biomarkers from this prior study in new cohorts of patients and controls, as a prerequisite for further development. Whole blood mRNA was purified from ATB patients recruited in the UK and India, LTBI and two groups of controls from the UK (i) a low TB incidence region (CNTRLA) and (ii) individuals variably-domiciled in the UK and Asia ((CNTRLB), the latter TB high incidence regions). Seventy-two mRNA biomarker gene targets were analyzed by qPCR using the Roche Lightcycler 480 qPCR platform and data analyzed using GeneSpring™ 14.9 bioinformatics software. Differential expression of fifty-three biomarkers was confirmed between MTB infected, LTBI groups and controls, seventeen of which were significant using analysis of variance (ANOVA): CALCOCO2, CD52, GBP1, GBP2, GBP5, HLA-B, IFIT3, IFITM3, IRF1, LOC400759 (GBP1P1), NCF1C, PF4V1, SAMD9L, S100A11, TAF10, TAPBP, and TRIM25. These were analyzed using receiver operating characteristic (ROC) curve analysis. Single biomarkers and biomarker combinations were further assessed using simple arithmetic algorithms. Minimal combination biomarker panels were delineated for primary diagnosis of ATB (both PTB and EPTB), LTBI and identifying LTBI individuals at high risk of progression which showed good performance characteristics. These were assessed for suitability for progression against the standards for new TB diagnostic tests delineated in the published World Health Organization (WHO) technology product profiles (TPPs)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Perumal, Abdullatif, Garlant, Honeyborne, Lipman, McHugh, Southern, Breen, Santis, Ellappan, Kumar, Belgode, Abubakar, Sinha, Vasan, Joseph and Kempsell.)

Epstein-Barr Virus (EBV) is associated with the Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL respectively). HIV is a risk factor for EBV infections and previously published data indicate that HIV infected individuals have higher chances of getting EBV infections compared to HIV uninfected individuals. Very limited information is available from India about the the prevalence of EBV in HIV positivity, with or without malignancy. In a recent study (Sinha et al. Current HIV Res 16:1-6, 2018) from All India Institute of Medical Sciences (AIIMS), New Delhi, we have shown that 2% among the HIV-1 infected individuals have malignancies including HL and NHL. To determine the prevalence of EBV among these individuals, clinical specimen obtained from ART clinic of AIIMS were tested for the presence of EBV DNA in plasma samples by quantitative real-time PCR. We have observed high prevalence of EBV (30%) among the 92 specimen tested. Prevalence is higher in patients with malignancy (37%) compared to those without maliganancy (27%). No correlation was observed with the CD4 counts or HIV viral load with EBV positivity., (© Indian Virological Society 2021.)

Global literature examining the association between mental health of women living with HIV (WLWH) and child development is scarce. In this study, we examined the relationship between mothers' mental health and their children's social development outcomes 6 months later. Data for these analyses come from several waves of interviews of 600 WLWH in the South Indian state of Andhra Pradesh, India. These women were enrolled in a 2×2 factorial clinical trial designed to assess the impact of food supplementation and nutrition education, both in addition to ASHA support, on adherence to ART and improved health outcomes for the women and one of their children. They were assessed on food security, stigma, social support, quality of life, depressive symptoms and child development outcomes. Results of longitudinal GEE regression analysis indicate that mother's depressive symptoms were significantly negatively associated with child's social quotient 6 months later. These findings have important implications for targeted health interventions, integrating mental health, both for WLWH and their children in India.

Background: Obstructive sleep apnoea (OSA) is an important factor in the development and progression of heart failure (HF). The prevalence of OSA is higher in patients with HF than in the general population. We sought to test the hypothesis that OSA severity was predictive of ventricular function and cardiac injury [as assessed by high-sensitivity cardiac troponin I(hs-cTnI)]., Methods: A total of 60 patients were recruited after evaluation for sleep disturbances using the Jenkins Sleep Questionnaire (JSQ) and Epworth Sleepiness Scale (ESS). Subsequently, they underwent polysomnography thus confirming the diagnosis of OSA and were equally divided into three groups according to OSA severity grade. Following polysomnography, the next morning patients underwent venous blood sampling and echocardiography., Results: We observed a statistically significant association (P = 0.009) between diastolic dysfunction grades and severity grades of OSA. All the three diastolic dysfunction variables E/A ratio, deceleration time and E/e' ratio had a significant association(P < 0.05) with severity grades of OSA. There was a marginally significant positive correlation (ρ = 0.3244, p = 0.04) between AHI events per hour and mitral E/e' ratio. There was a statistically significant association(P < 0.001) between hs-cTnI value among different severity grades of OSA., Conclusions: Here in our study, we found OSA a potential risk factor for development of myocardial injury and diastolic dysfunction. Severe grades of OSA are associated with higher grades of diastolic dysfunction and circulating levels of hs-cTnI. These data are consistent with the notion of a vicious cycle of frequent apnoea's or hypoxemia and recurrent myocardial injury, which could increase the risk of heart failure especially diastolic dysfunction in OSA., Competing Interests: Conflict of interest All authors declare that they have no credit and conflict of interest. ResMed provided a philanthropic donation to UC San Diego School of Medicine, San Diego 92121, CA, USA., (Copyright © 2020 Elsevier B.V. All rights reserved.)