Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

A 37-Year-Old Man With Dyspnea, Bilateral Lung Consolidation, and a Tracheal Mass.

CASE PRESENTATION: A 37-year-old man presented to the ED with symptoms of productive cough, self-reported fever, and shortness of breath for the past 15 days. He was placed on noninvasive mechanical ventilation for respiratory distress. IV piperacillin-tazobactam and inhaled bronchodilators were promptly administered, and he was subsequently transferred to the respiratory ICU for further care. He had no history of bowel and bladder disturbance, altered sensorium, swelling of feet, or abdominal distention. He never used tobacco and denied a history of TB. Medical history was notable for recurrent hospitalizations and administration of multiple courses of antibiotics in the past for similar complaints. He often used inhaled bronchodilators/corticosteroids when clinically stable to relieve symptoms.

Post COVID sequelae among COVID-19 survivors: insights from the Indian National Clinical Registry for COVID-19.

INTRODUCTION: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities. METHODS: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting. RESULTS: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03). CONCLUSION: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Health system factors related to COVID-19 mortality in Eastern India: Hospital-based cross-sectional study.

Introduction: Mortality from coronavirus disease 2019 (COVID-19) pandemic has left footprints across all ages and socio-economic strata. The deaths because of COVID-19 are usually multi-factorial. The study aimed to assess the health system factors related to COVID-19-related deaths. Materials and Methods: A hospital-based retrospective study was conducted at a tertiary care hospital of eastern India. A total of 272 COVID-19 deaths that occurred between April and November 2020 were investigated. Data were extracted from Medical Record Department, and telephonic interviews were conducted to assess the different delays related to death. Data were analysed using Statistical Package for Social Sciences. Travel time, travel distance, delay in testing, and delay in receiving quality care were presented as median with inter-quartile range. Results: Complete information could be collected from 243 COVID deaths of the 272 deaths (89.3%). The duration of hospital stay was 1-7 days for 42% of the deceased. The median travel time was 120 min, and the median distance travelled was 60 km. The median time to receive first attention of health care workers was 10 minutes. There was hardly any delay in reporting of test results, whereas the median time from symptoms to test and the median time from symptoms to admission were 4 days each. Conclusion: Health system factors related to death of COVID-19 need to be addressed to avoid the avoidable deaths during the pandemic situation. The resilience of the health system can be helpful in reducing death toll in a low-resource country like India.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Dextromethorphan premedication in the alleviation of cough during flexible bronchoscopy in adults: A randomized double-blind placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Cough is invariably encountered during flexible bronchoscopy despite sedation and topical anaesthetics. The ideal cough suppressant during flexible bronchoscopy is not known. We assessed the role of dextromethorphan premedication in relieving the cough during flexible bronchoscopy in adults. METHODS: In this single-centre study, we randomized patients aged ≥18 years to receive dextromethorphan syrup 30 ml (90 mg) or an equal volume of placebo 1 h before the procedure. Patients rated their cough severity and discomfort on a visual analogue scale at the end of the procedure. Bronchoscopists also rated cough severity at the end of the procedure. RESULTS: Out of 112 patients screened, 94 patients (median (interquartile range [IQR]) age 51 (36.25-60.75) years, male: female 2.13:1) were randomized to either the dextromethorphan (n = 47) or placebo (n = 47) groups. The patients-rated median (IQR) cough scores at the end of the procedure were 15 (10-23) mm in dextromethorphan versus 20 (12-45.5) mm in placebo groups (p = 0.03). Patients-rated median cough scores at 1 h (5 mm vs. 6 mm, p = 0.21), discomfort scores (12.5 mm vs. 12.5 mm, p = 0.49), and midazolam and lignocaine usage were similar between the two groups. The bronchoscopist-rated median cough score was non-significantly lower in the intervention compared to the placebo (26 mm vs. 35 mm, p = 0.09) groups. CONCLUSION: Dextromethorphan premedication 1 h before flexible bronchoscopy may have an additive effect on cough suppression under conscious sedation and topical lignocaine. Further trials are needed to reiterate our findings with certainty.

Clinico-Epidemiological Characteristics of Healthcare Workers with SARS-CoV-2 Infection during the First and Second Waves in a Teaching Hospital from Eastern India: A Comparative Analysis.

In this retrospective observational study, we have performed a comparative analysis of the demographic, clinical and epidemiological characteristics of the HCWs affected with SARS-CoV-2 infection during first two waves in India. The overall prevalence of SARS-CoV-2 infection among HCWs was found to be 15.24% (14.20-16.33) and 23.38% (22.14-25.65) during first and second waves respectively. The second wave showed an adjusted odds ratio of 0.04(0.02-0.07) and 2.09(1.49-2.93) for hospitalization and being symptomatic, respectively. We detected significantly higher level of C-reactive protein (CRP) among admitted HCWs during the second wave (5.10 -14.60 mg/dl) as compared to the first wave (2.00 - 2.80 mg/dl). Our study found the relative risk of SARS-CoV-2 reinfection among HCWs during the second wave to be 0.68 [0.57-0.82, p < 0.001)]. Although, the prevalence of SARS CoV-2 infection and risk of being symptomatic was higher during second wave, the risk of hospitalization was less when compared with the first wave.

Spectrum of Bacterial Pathogens in Critical COVID-19 Patients Admitted in Intensive Care Units of a Tertiary Care Hospital During the First and Second Wave of the Pandemic.

OBJECTIVE: This study intends to compare the clinical characteristics and the prevalence and spectrum of bacterial pathogens in COVID-19 patients admitted to ICU during the first and second waves at a tertiary care, teaching and referral hospital of eastern India. METHOD: This is a hospital-based retrospective study which analysed demographic details, clinical profile and bacterial culture results of severe and critically ill COVID-19 patients admitted in intensive care units (ICU) during April -Oct 2020 (1st wave) and April -July 2021 (2nd wave). RESULT: The patients admitted during the 2nd wave were comparatively older and had multiple comorbidities compared to the 1st wave. (23.8%) (45/189) and 50% (173/346) of the COVID-19 patients admitted to ICU developed bacterial infection during the 1st and 2nd wave respectively. Overall, there was predominance of multidrug resistant Gram negative bacilli in both the waves. There was increased isolation of intrinsic colistin resistant microorganisms. CONCLUSION: Multidrug resistant Gram negative bacterial infections, remain a dreaded complication in severe and critically ill hospitalised COVID-19 patients requiring ICU care and high usage of colistin spirals the emergence and spread of pathogens intrinsically resistant to colistin.

Pulmonary anaplastic large-cell lymphoma: A case-based systematic review of world literature.

We describe a case of ALK1 negative (-) pulmonary anaplastic large-cell lymphoma (pALCL) in an adult female with an unfavorable outcome following combination chemotherapy and present a systematic review of 39 such sporadic cases reported over the past 28 years (1990-2018). pALCL occurred in 26 males and 13 females (median age, 43 years [5-81]) and 13/39 (33.33%) were ≤18 years. The lesions were endobronchial in 21 (53.85%) and parenchymal in 18 (46.15%) cases. Twenty-six cases were ALK1-; 13 were ALK1+ (positive); and 27/34 cases had a T cell phenotype (where tested). ALK- cases were characterized by higher age (P = 0.012) at presentation, more B symptoms (P = 0.002), and more parenchymal than endobronchial lesions (P = 0.039). The median survival (N = 29/39) was 60 months; pediatric group had a better survival than adult/elderly group (log-rank, P = 0.026). pALCL is rare and may have a distinct biological behavior.

Robust home brew fragment sizing assay for detection of MET exon 14 skipping mutation in non-small cell lung cancer patients in resource constrained community hospitals.

BACKGROUND: A mutation/deletion involving donor or acceptor sites for exon 14 results in splicing out of exon 14 of the mesenchymal epithelial transition (MET) gene and is known as "MET exon 14 skipping" (ΔMET14). The two recent approvals with substantial objective responses and improved progression-free survival to MET inhibitors namely capmatinib and tepotinib necessitate the identification of this alteration upfront. We herein describe our experience of ΔMET14 detection by an mRNA-based assay using polymerase chain reaction followed by fragment sizing. METHODS: This is a home brew assay which was developed with the concept that the transcripts from true ΔMET14 will be shorter by ~140 bases than their wild type counterparts. The cases which were called MET exon 14 skipping positive on next-generation sequencing (NGS) were subjected to this assay, along with 13 healthy controls in order to establish the validity for true negatives. RESULTS: Thirteen cases of ΔMET14 mutation were detected on NGS using RNA-based sequencing. Considering NGS as a gold standard, the sizing assay using both gel and capillary electrophoresis that showed 100% specificity for both with concordance rates of 84.6% and 88.2% with NGS, respectively, were obtained. CONCLUSIONS: Owing to the cost-effective nature and easy to use procedures, this assay will prove beneficial for small- and medium-sized laboratories where skilled technical personnel and NGS platforms are unavailable.

Comparison of endobronchial ultrasound-guided transbronchial needle aspiration cytology versus cell blocks in adults with undiagnosed mediastinal lymphadenopathy.

INTRODUCTION: Retrospective studies have shown improved diagnostic yield of combined cytology and cell blocks specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with variable additional yields in cell blocks. In this prospective study, we assessed the diagnostic performance of cytology and cell blocks in patients undergoing EBUS-TBNA. METHODS: This was a single-center, cross-sectional study conducted between December 2017 and November 2019 including patients aged ≥18 years with mediastinal lymphadenopathy. EBUS-TBNA was performed under conscious sedation using 22G needles. Both cytology smears and cell blocks by the tissue coagulum clot technique were prepared for each patient without rapid on-site evaluation. RESULTS: Data were analyzed for 93 patients (mean age 54.25 ± 13.7 years, 73 males) where both cytology and cell blocks were available. Sample adequacy was 100%. Overall diagnostic yield either by cytology or cell block was 83%. Cytology yield was 79.6%, whereas cell block was diagnostic in 73% of patients (P < 0.001). The overall additional yield of cell blocks was 3.2%. Cell blocks had additional yields of 1.8%, 0%, and 14.3% in malignancy, tuberculosis, and sarcoidosis, respectively. Tumor histology was better identified in 76% of positive cell blocks, and accurate histological subtyping was possible in 32.6% cases. Immunohistochemistry was feasible in 82.5% of all positive cell blocks, and these were judged to be adequate for the mutational analysis. CONCLUSIONS: Compared to cytology, EBUS-TBNA cell blocks did not significantly increase the overall diagnostic yield in unselected patients. However, cell blocks are beneficial in the characterization of tumor morphology and histological subtyping of lung cancer.

Concomitant echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase rearrangement and epidermal growth factor receptor mutation in non-small cell lung cancer patients from eastern India.

BACKGROUND: In non-small cell lung cancer common driver mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are usually mutually exclusive. This study aimed to elucidate the concurrence of EGFR mutation and ALK rearrangement in eastern India patients with primary lung adenocarcinoma and assess the response of EGFR tyrosine kinase inhibitor (TKI) therapy after 6 months in primary lung adenocarcinoma. METHODS: We retrospectively analyzed 198 adenocarcinomas for EGFR and ALK mutations. EGFR and ALK tests were done by real-time polymerase chain reaction and immunohistochemistry (IHC) techniques, respectively. Radiological response was assessed by Response Evaluation Criteria in Solid Tumors (version 1.1). RESULTS: EGFR/ALK co-alteration was found in 4 adenocarcinoma patients. All were males with advanced disease. Younger patients had exon 19 deletion whereas older ones showed exon 21 mutation. The initial option of ALK-TKI in all four patients was excluded straightaway due to the high-cost burden of ALK-TKI. Two of them showed a partial response while other two had stable disease after 6 months of EGFR TKI therapy. CONCLUSION: EGFR/ALK co-alterations in adenocarcinomas albeit rare do exist. The challenge of monetary hurdle in developing countries with ALK TKI therapy can be handled by giving only EGFR TKI in these cases of concomitant mutations. Future perspective in research could be finding an agent with the potential of dual inhibition of ALK and EGFR.

ROS1 positive non-small cell lung cancer with pulmonary embolism in a 22-year woman.

ROS1-rearrangement occurs in 1-2% of non-small cell lung cancer (NSCLC). This mutation is predominantly seen in relatively young, non-smoker, female with adenocarcinoma. Association of pulmonary embolism with ROS1-rearranged NSCLC has been suggested. We report a case of a 22-year-old woman with ROS1-positive NSCLC and pulmonary embolism. This case possibly represents the youngest patient in the literature.

CSF cell-free DNA EGFR testing using DdPCR holds promise over conventional modalities for diagnosing leptomeningeal involvement in patients with non-small cell lung cancer.

BACKGROUND: EGFR mutant NSCLC patients have leptomeningeal (LM) involvement in more than 9% cases. MATERIAL & METHODS: We conducted a study evaluating the diagnostic utility of cfDNA EGFR testing in CSF using DdPCR while comparing it against MRI and CSF cytology. We also looked for known EGFR mutations in the CSF sample. These mutations were also tested in paired plasma samples. We further compared which constituent of CSF (pellet/supernatant) had better yield. RESULTS: 21 patients comprised the study. Of these 17 patients were diagnosed to have LM involvement based on conventional criteria. All modalities had 100 % specificity and positive predictive value. However, MRI and CSF cytology had a poor negative predictive value. cfDNA had the highest sensitivity (92.3 %), negative predictive value (75 %), accuracy (94.1 %), and net comparative benefit. Paired plasma samples were available for 19 patients. Primary EGFR mutation was detectable in the CSF sample in 16/19 patients; however, the plasma sample was positive only in 7/19 patients. 3 samples were negative for primary EGFR mutation in both CSF and plasma. None of the CSF samples showed positivity for T790M mutation which could however be observed in two patients in plasma samples. Both supernatant and pellet were analysed for cfDNA mutation analysis in 18/21 patients. The intraclass correlation coefficient regarding the percentage fraction tumor-derived DNA of cfDNA observed was 0.83(95 % CI 0.29 to 0.95) between both samples. CONCLUSION: EGFR detection in CSF has a potential role in diagnosing LM involvement. T790 M resistance mutations are uncommon in CSF post first and second-generation TKIs. Both supernatant and pellet samples can be used for the extraction of cell-free DNA in CSF.

Late manifestation of follicular conjunctivitis in ventilated patient following COVID-19 positive severe pneumonia.

A 65-year-old known diabetic, hypertensive, and asthmatic patient was admitted for suspected coronavirus disease 19 (COVID-19) infection following complaints of breathlessness. He tested positive for COVID-19 and was put on ventilation. He developed severe follicular conjunctivitis of the right eye while on a ventilator, which was treated conservatively. The resolution of ocular signs was noted over 2 weeks without any complications. This case highlights the timeline of events and discusses the late ophthalmic manifestations in patients with COVID-19 infection.

Rasmussen's aneurysm masquerading as mass lesion.

Haemoptysis is an often encountered respiratory symptom. The amount of haemoptysis varies from mild to life-threatening severity and may indicate the underlying pulmonary disorder. Herein, we report a 50-year-old male smoker who presented with occasional streaky to mild haemoptysis for last 1 year. He had pulmonary tuberculosis 10 years ago and had received adequate treatment. Chest radiograph was suspicious of a mass lesion in left upper lung. Contrast-enhanced CT scan of thorax revealed pulmonary artery pseudoaneurysm suggestive of Rasmussen's aneurysm. Unlike this case, Rasmussen's aneurysm usually manifests as life-threatening haemoptysis and portends a high mortality.