Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection- a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Impact of post-COVID-19 lung damage on pulmonary function, exercise tolerance and quality of life in Indian subjects.

After recovery from COVID-19, there is data to suggest potential long-term pulmonary sequelae and associated impairment of functional capacity. This cross-sectional study was designed to assess the impact on respiratory function in a cohort of Indian subjects. Subjects who had recovered from COVID-19 were recruited. Clinical symptoms, pulmonary function test results, 6-minute walk test (6MWT) results, St George's Respiratory questionnaire (SGRQ) and chest radiographs were obtained. Information on the COVID-19 illness during hospitalization, baseline laboratory biomarkers and the disease severity categories as outlined by WHO (asymptomatic, mild, moderate, severe and critical), were retrieved from the hospital records. The 'COVID pneumonia'(WHO category moderate, severe & critical) group was compared with the 'Mild COVID' (WHO category mild) group and likewise, the WHO category moderate and the WHO category severe/critical groups were compared. In 207 subjects, whose mean age was 48.7 years were assessed after an average of 63 days from onset of symptom, 35% had TLC< 80% (restrictive defect), 8.3% had FEV1/FVC<70% (obstructive defect) and 44.4% had diminished DLCO<80% (diffusing capacity). The 'COVID-19 pneumonia' group when compared to the 'mild COVID-19' group, had lower FVC% (77.85 VS 88.18; P = 0.001), TLC% (79.48 VS 87.91; P = 0.0002), DLCO% (75.30 VS 89.20; P<0.0001) and DLCO/VA% (105.6 VS 111.8; P = 0.032), decreased minimum oxygen saturation (94.89 VS 97.73; P<0.0001) and more subjects had a drop in saturation of ≥ 4% (21.69% VS 4.84%; P = 0.001) during the 6MWT, and a greater mean total SGRQ score (29.2 VS 11.0; P<0.0001). To our knowledge, this is the first such report on Indian subjects. We have shown that post-COVID-19 lung damage leads to significant impairment of lung function, quality of life and effort tolerance.

Tuberculin test using Indian indigenous purified-protein derivative (PPD) shows only moderate agreement with international standard PPD.

Background: In India, the prevalence of Latent TB infection (LTBI) is estimated to be around 40%. Various formulations of PPD(Purified protein derivative) are available, for diagnosis of LTBI, which may give variable responses. The commercially available PPD in India is by Arkray Healthcare (TST-Arkray). It is unclear if this product may have a similar sensitivity compared to other internationally accepted tuberculins (TST-Tubersol). Objectives: To assess the performance of the two TSTs compared to Quantiferon-Gold Plus (QFT-Plus). Methodology: A blood sample was collected for the QFT-Plus test. Both the TSTs were placed in the right and the left volar aspect of the forearms and 48 hrs later, the subjects came back to the study site for reading. Results: Among the 512 participants who were recruited, 326 subjects were healthcare professionals and 186 subjects were household contacts of patients with tuberculosis. They were tested with both TST-Tubersol and TST-Arkray, 139(27 %) participants tested positive for TST-Tubersol (≥10 mm), whereas 203 participants (40.1 %)tested positive for TST-Arkray. There was moderate agreement between the two tests with k = 0.58. Also, there was only poor agreement between both the TSTs with QFT Plus(kappa = 0.19 for Tubersol and 0.17 for Arkray). With QFT-Plus as gold standard, the sensitivity, specificity, PPV and NPV of TST-Tubersol, ast an induration cut-off of 10 mm was 46.8 %,76.3 %,31.8 % and 85.8 %. respectively and TST- Arkray; 60.6 %, 64 %, 28.5 % and 87.2 % respectively. Conclusion: The Indian TST (Arkray Diagnostics) has shown moderate agreement with the internationally accepted Tubersol. Additionally, there was poor agreement between the TSTs and QFT plus test.

Biomarkers of coagulation, endothelial, platelet function, and fibrinolysis in patients with COVID-19: a prospective study.

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7-14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26-4.55 ng/ml; Soluble P-selectin = 13.5-31.5 ng/ml; BTG = 0.034-1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.

Tracheobronchopathia Osteochondroplastica - to Biopsy or not to Biopsy? A Relook at The Rare Disease.

BACKGROUND: Tracheobronchopathia osteochondroplastica (TPO) is a rare idiopathic disease involving the tracheobronchial tree. It is mostly an incidental finding with non-specific clinical manifestations. It has typical bronchoscopic, radiological features and biopsy is usually considered non-essential. The study aimed to determine whether biopsy makes a difference in the management of patients. METHODS: All patients diagnosed with TPO in our institution over 15 years (2005 to 2020) were included in this study. Their medical records, chest computed tomography (CT), and bronchoscopy reports were retrospectively reviewed, and data were analysed. All the CT images were reviewed by a senior chest radiologist. RESULTS: From the 20,000 bronchoscopies and 260,000 CT thorax images obtained, 28 cases were diagnosed as TPO based on either bronchoscopy or radiology or both. Among the 19 cases diagnosed through bronchoscopy, 16 underwent a biopsy. In addition to TPO features, biopsy showed additional diagnoses in 6 cases. In 9 cases, TPO was not initially diagnosed by CT but by bronchoscopy. In 8 patients, TPO was diagnosed incidentally on CT performed for other reasons. On follow-up with the treatment of underlying/co-existing concomitant aetiologies, clinical improvement was noted in all patients. None of them progressed to respiratory failure or airway obstruction until the last follow-up. CONCLUSION: Among patients who underwent bronchoscopic biopsy of TPO lesions, 38% had biopsy results showing an alternative aetiology, which led to changes in the treatment plan for all these patients. Hence, a bronchoscopic biopsy of TPO lesions should be performed to rule out other aetiologies.

Reversible platypnoea-orthodeoxia syndrome.

Platypnoea-orthodeoxia syndrome is characterised by dyspnoea and oxygen desaturation in the upright position usually caused by an extracardiac shunt and less often due to dynamic factors that accentuate an intracardiac right-to-left shunt. In our patient, the collapse of lower lobe of left lung secondary to bronchial stenosis due to endobronchial tuberculosis and resultant mediastinal shift was the factor that led to an otherwise unrecognised intracardiac right-to-left shunt leading to platypnoea-orthodeoxia. We postulate that there would have been an increased stretching and widening of a patent foramen ovale in the upright position due to gravity resulting in an increased shunt despite normal intracardiac pressures. Once the patency of the left main bronchus was restored by deploying a stent, the left lower lobe expanded, the mediastinum returned to its normal position and there was resultant resolution of the platypnoea-orthodeoxia. This interesting observation may be useful in managing similar scenarios in the future.

Bronchoscopic view of post-tuberculosis lung cavity: A case report.

An elderly male, a former smoker, was evaluated at the pulmonary medicine clinic for recurrent episodes of streaky hemoptysis for the last 3 years. He had a history of being successfully treated for microbiologically confirmed pulmonary tuberculosis in the past. He presented in this consultation with two episodes of large volume hemoptysis, and the laboratory results suggested an ongoing active infection. Sputum smear was negative for an infectious etiology. Contrast-enhanced CT of the thorax revealed a lung cavity in the right upper lobe. He underwent flexible bronchoscopy with bronchoalveolar lavage which revealed Klebsiella pneumoniae infection. Small-diameter bronchoscope was used to navigate into the affected lung segment which revealed a cave-like appearance. This was an interesting finding and physicians should be familiar with such bronchoscopic findings and techniques in the management of their patients, particularly in tuberculosis endemic areas.

Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?

BACKGROUND: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic, a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction. AIM: To describe the clinical and laboratory characteristics, outcomes, and management of these patients, and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders. METHODS: This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital, between May and August 2021, who fulfilled clearly defined inclusion and exclusion criteria. Outcome was assessed by a change in PaO2/FiO2 ratio and levels of inflammatory markers before and after immunomodulation, duration of mechanical ventilation after starting treatment, and survival to discharge. RESULTS: Five patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction at a median interquartile range (IQR) duration of 32 (23-35) d after the onset of symptoms. These patients had elevated inflammatory markers, required mechanical ventilation for 13 (IQR 10-23) d, and responded to glucocorticoids and/or intravenous immunoglobulin. One patient died (20%). CONCLUSION: This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome - Adults by the paucity of extrapulmonary organ involvement. The diagnosis can be considered in patients presenting with delayed respiratory worsening, that is not attributable to cardiac dysfunction, fluid overload or ongoing infections, and associated with an increase in systemic inflammatory markers like C-reactive protein, inteleukin-6 and ferritin. A good response to immunomodulation can be expected. This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.

Rural South Indian spirometry values show wide variation compared to existing prediction equations.

Background and Objective: India, a highly heterogeneous country, has no common reference standards for predicting spirometry values, with very few recent studies from south India. This study aimed to create reference equations for rural south Indian adults, based on a population-based survey in Vellore, south India and compare it with other equations from India. Methods: The data from 583 non-smoking, asymptomatic participants (30 years and older) from a spirometry-based survey for airflow obstruction (rural Vellore, 2018), were used to develop equations for FEV1, FEV1/FVC, and FVC. The dataset was divided for development (70%) and validation (30%), by gender. Differences between observed and predicted values were assessed using the new equations and comparisons made with other equations from India. Results: Predictions with Vellore rural equations were closest to the previous south Indian equations from urban Bangalore. However, the Bangalore equations led to overestimation of FVC values in males, and of both FEV1 and FVC values in females. Using the rural Vellore equations also led to a higher percent of males being classified as having airflow obstruction, compared to the Bangalore equations which underestimated airflow obstruction in this rural population. Comparison with previously derived Indian equations from other parts of the country showed pronounced variations. Conclusions: Our study reiterates the need for representative rural and urban studies of adults from various parts of India, to obtain region specific reference equations, given the wide variations in spirometry values in "normal" individuals, due to social heterogeneities of the Indian population and resulting complexities in defining normal.

Undiagnosed Asthma-COPD overlap among patients diagnosed as Asthma and COPD in a referral hospital, India.

Patients who have features of both Asthma & COPD are now known as Asthma COPD overlap (ACO). Prevalence of ACO based on the Global Initiative for Asthma (GINA) and Global initiative for obstructive lung disease (GOLD) Syndromic Approach is scarce. In this cross-sectional observational study, we recruited physician-diagnosed-pAsthma, pCOPD & pACO by simple random sampling. Clinical features, spirometry, 6-min walk test, Serum Immunoglobulin E, % blood eosinophils and chest x-rays were reviewed. Syndromic approach was applied, and the diagnosis was reclassified accordingly. In all, 877 patients were included (Male = 445, Female = 432). Physician diagnosis for these were: pAsthma-713, pCOPD-157 and pACO-7. They were reclassified using the Syndromic approach as: sAsthma, sCOPD and sACO. The 713 pAsthmatics were reclassified as follows: sAsthma-684 (95.94%), sCOPD-12 (1.68%) and sACO-17 (2.38%). Of the 157 pCOPD patients, 91 (57.96%) were reclassified as sCOPD, 23 (14.6%) as sACO, and 17 (927.38%) as sAsthma. Of the 7 previously diagnosed pACO patients, only 1 (14.28%) was reclassified as sACO, 5 (71.42%) as sAsthma and 1 (14.28%) as sCOPD. sCOPD patients had more exacerbations (52.88% vs 46.34%, p = 0.479), critical care admissions (16.35% vs 7.32%, p = 0.157) and intubations (17.31% vs 9.76%, p = 0.255) compared to sACO patients, the latter had more events than sAsthma patients: exacerbations 46.34% vs 10.11% (p < 0.001), critical care admissions 7.32% vs 1.64% (p = 0.010) and intubations 9.76% vs 1.5% (p < 0.001). The syndromic approach helped us to identify ACO and also more appropriately classified COPD & Asthma. There was a significant difference between physician diagnosis and diagnosis using Syndromic Approach. It revealed considerable misclassification of several Asthmatic and ACO subjects, who could have been denied inhaled corticosteroids, as they were wrongly categorised as COPD by physician diagnosis.

Pharmacokinetics of rifampicin, isoniazid & pyrazinamide during daily & intermittent dosing: A preliminary study.

Background & objectives: The National Tuberculosis (TB) Control Programme has transitioned from thrice-weekly to daily drug treatment regimens in India. This preliminary study was conceived to compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in TB patients being treated with daily and thrice weekly anti-TB treatment (ATT). Methods: This prospective observational study was undertaken in 49 newly diagnosed adult TB patients receiving either daily ATT (n=22) or thrice-weekly ATT (n=27). Plasma RMP, INH and PZA were estimated by high-performance liquid chromatography. Results: The peak concentration (Cmax) of RMP was significantly higher (RMP: 8.5 µg/ml vs. 5.5 µg/ml; P=0.003) and Cmax of INH was significantly lower (INH: 4.8 µg/ml vs. 10.9 µg/ml; P<0.001) in case of daily dosing compared to thrice-weekly ATT. Cmax of drugs and doses was significantly correlated. A higher proportion of patients had subtherapeutic RMP Cmax (8.0 µg/ml) during thrice-weekly compared to daily ATT (78% vs. 36%; P=0.004). Multiple linear regression analysis showed that Cmax of RMP was significantly influenced by the dosing rhythm, pulmonary TB and Cmax of INH and PZA by the mg/kg doses. Interpretation & conclusions: RMP concentrations were higher and INH concentrations were lower during daily ATT, suggesting that INH doses may need to be increased in case of a daily regimen. Larger studies are, however, required using higher INH doses when monitoring for adverse drug reactions and treatment outcomes.

Clinical management of stage III non-small cell lung cancer in India: An expert consensus statement.

Non-small cell lung cancer (NSCLC) is considered the most common type of lung cancer (>80% of all lung cancers); patients are often diagnosed at advanced stages of the disease. The management of NSCLC is considered challenging owing to variations in size, an extension of the tumors, involvement patterns, and classification. Although adequate literature and guidelines are available on the management of NSCLC in several countries, an Indian perspective on stage III NSCLC management is lacking. We used the modified Delphi approach to form consensus statements. A thorough literature search was done. The authors then convened and deliberated over published literature, available guidelines, and clinical judgment. Recommendation statements were formed for different clinical scenarios. These statements were sent as a form of survey to other oncologists, and their responses were recorded and mentioned. Evidence-based statements were formed for diagnosing and managing stage III NSCLC. These recommendation statements cover various aspects-surgical, radiation, and medical treatment in various clinical scenarios including adjuvant, neoadjuvant, and consolidation therapies.

Evaluation of humoral immune deficiency in Indian patients with bilateral bronchiectasis with no apparent aetiology.

Background: Infections continue to be the leading aetiology of bronchiectasis in developing countries like India. Among non-infectious cases, the majority will have no identifiable cause despite extensive evaluation. Recently, immunodeficiency has been recognized as an important aetiology, but data on its prevalence remain rather sparse. Objectives: The objective of this study is to evaluate the prevalence of humoral immunodeficiency in a cohort of adults with bilateral bronchiectasis with no apparent aetiology. Methods: This is the single-site study from Christian Medical College (Vellore, India) of adults with HRCT-proven non-infectious bronchiectasis. Humoral immunity was assessed through quantitative analysis of immunoglobulins and IgG subclass levels. Results: Among 158 cases, immunoglobulin deficiency was found in 15%. Low IgM was the most predominate finding (7%), followed by common variable immunodeficiency (3%) and low IgA (2.5%). In addition, IgG subclass deficiency was found in 5%. In 53% of cases, no specific aetiology could be identified. Conclusion: Humoral immune deficiency is present in a significant proportion of patients with non-infectious bronchiectasis. Routine measurement of serum immunoglobulins should therefore be considered as part of the evaluation.

Impact of Undernutrition on Tuberculosis Treatment Outcomes in India: A Multicenter, Prospective, Cohort Analysis.

BACKGROUND: Undernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined. METHODS: We conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at 5 sites from 2015-2019. Using multivariable Poisson regression, we assessed associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after 2 months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion. RESULTS: Severe undernutrition (BMI <16 kg/m2) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR], 2.05; 95% confidence interval [CI], 1.42-2.91 and aIRR, 2.20; 95% CI, 1.16-3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR, 1.81; 95% CI, 1.27-2.61). Severe stunting (height-for-age z score <-3) was associated with unfavorable outcomes (aIRR, 1.52; 95% CI, 1.00-2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a 4- and 5-fold higher rate of death, respectively. CONCLUSIONS: Premorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need to address this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.

Semantic segmentation of bone structures in chest X-rays including unhealthy radiographs: A robust and accurate approach.

The chest X-ray is a widely used medical imaging technique for the diagnosis of several lung diseases. Some nodules or other pathologies present in the lungs are difficult to visualize on chest X-rays because they are obscured byoverlying boneshadows. Segmentation of bone structures and suppressing them assist medical professionals in reliable diagnosis and organ morphometry. But segmentation of bone structures is challenging due to fuzzy boundaries of organs and inconsistent shape and size of organs due to health issues, age, and gender. The existing bone segmentation methods do not report their performance on abnormal chest X-rays, where it is even more critical to segment the bones. This work presents a robust encoder-decoder network for semantic segmentation of bone structures on normal as well as abnormal chest X-rays. The novelty here lies in combining techniques from two existing networks (Deeplabv3+ and U-net) to achieve robust and superior performance. The fully connected layers of the pre-trained ResNet50 network have been replaced by an Atrous spatial pyramid pooling block for improving the quality of the embedding in the encoder module. The decoder module includes four times upsampling blocks to connect both low-level and high-level features information enabling us to retain both the edges and detail information of the objects. At each level, the up-sampled decoder features are concatenated with the encoder features at a similar level and further fine-tuned to refine the segmentation output. We construct a diverse chest X-ray dataset with ground truth binary masks of anterior ribs, posterior ribs, and clavicle bone for experimentation. The dataset includes 100 samples of chest X-rays belonging to healthy and confirmed patients of lung diseases to maintain the diversity and test the robustness of our method. We test our method using multiple standard metrics and experimental results indicate an excellent performance on both normal and abnormal chest X-rays.

Treatment of COVID-19 Acute Respiratory Distress Syndrome With a Tabletop Noninvasive Ventilation Device in a Respiratory Intermediate Care Unit.

Objective: To study the outcomes of noninvasive ventilation (NIV) administered through a tabletop device for coronavirus disease 2019 acute respiratory distress syndrome in the respiratory intermediate care unit (RIMCU) at a tertiary care hospital in India. Patients and Methods: We retrospectively studied a cohort of hospitalized patients deteriorating despite low-flow oxygen support who received protocolized management with positive airway pressure using a tabletop NIV device in the RIMCU as a step-up rescue therapy from July 30, 2020 to November 14, 2020. Treatment was commenced on the continuous positive airway pressure mode up to a pressure of 10 cm of H2O, and if required, inspiratory pressures were added using the bilevel positive air pressure mode. Success was defined as weaning from NIV and stepping down to the ward, and failure was defined as escalation to the intensive care unit, the need for intubation, or death. Results: In total, 246 patients were treated in the RIMCU during the study period. Of these, 168 received respiratory support via a tabletop NIV device as a step-up rescue therapy. Their mean age was 54 years, and 83% were men. Diabetes mellitus (78%) and hypertension (44%) were the commonest comorbidities. Treatment was successful with tabletop NIV in 77% (129/168) of the patients; of them, 41% (69/168) received treatment with continuous positive airway pressure alone and 36% (60/168) received additional increased inspiratory pressure via the bilevel positive air pressure mode. Conclusion: Respiratory support using the tabletop NIV device was an effective and economical treatment for coronavirus disease 2019 acute respiratory distress syndrome. Further studies are required to assess the appropriate time of initiation for maximal benefits and judicious utilization of resources.

The role and diagnostic accuracy of serology for COVID-19.

BACKGROUND: The role and performance of various serological tests for the diagnosis of COVID-19 are unclear. This study aimed to evaluate the performance of seven commercially available serological assays for SARS-CoV-2 antibodies by testing COVID-19 cases and controls. METHODS: Adult patients with fever for > 5 days, admitted to a tertiary-care teaching hospital in South India, were enrolled prospectively between June and December 2020. SARS-CoV-2 RT-PCR confirmed patients were classified as cases, and patients with febrile illness with laboratory-confirmed alternative diagnosis and healthy participants were controls. All participants were tested with SCoV-2 Detect™ IgM ELISA kit and SCoV-2 Detect™ IgG ELISA kit (InBios International, Seattle, USA) (Inbios), SARS-CoV-2 Total and SARS-CoV-2 IgG (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) (Siemens), Roche Elecsys® Anti-SARS-CoV-2 (Roche Diagnostics, Rotkreuz, Switzerland) (Roche), Abbott SARS-CoV-2 IgG (Abbott Diagnostics, IL, USA) (Abbott), and Liaison® SARS-CoV-2 S1/S2 IgG (DiaSorinS.p.A., Saluggia, Italy) (Liaison). The sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and accuracies were compared. RESULTS: There were 303 participants: 153 cases and 150 controls. ELISA detecting anti-S protein antibody was more sensitive (88.9% for IgG and 86.3% for IgM) than the CLIAs (82.4% for total antibodies and 76.5-85.6% for IgG). Among CLIAs, Roche IgG was most sensitive (85.6%) followed by Abbott (83%) and Liaison (83%). Abbot had the best PPV (88.8%) and was more specific (89.3%) than Liaison (82%) and Roche (82%). Siemens IgG was less sensitive (76.5%) than Siemens Total (82.4%). The specificity of all the serological assays was modest (75-90%). Antibody test positivity increased with the duration of illness reaching 90% after 10 days of illness. When cases were compared against pre-pandemic controls, the IgG gave excellent specificity (98-100%). For seroprevalence studies, InBios IgG had the best accuracy (90.8%) with 88.9% sensitivity and 97.6% specificity. CONCLUSION: The serological assays are important adjuncts for the diagnosis of COVID-19 in patients with persistent symptoms, especially in the second week of illness. The value of serological diagnostic tests is limited in the first week of illness and they provide additional value in seroprevalence studies. The diagnostic accuracy of the ELISA and CLIA platforms were comparable.

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.