Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial.

BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared. DISCUSSION: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice. TRIAL REGISTRATION: This clinical trial has been registered prospectively on www. CLINICALTRIALS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.

Association of the C allele of rs479200 in the EGLN1 gene with COVID-19 severity in Indian population: a novel finding.

The present study investigated two single nucleotide polymorphisms (SNPs)-rs479200 and rs516651 in the host EGLN1/PHD2 gene for their association with COVID-19 severity. A retrospective cohort of 158 COVID-19 patients from the Indian population (March 2020 to June 2021) was enrolled. Notably, the frequency of C allele (0.664) was twofold higher than T allele (0.336) in severe COVID-19 patients. Here, we report a novel finding that the C allele of rs479200 in the EGLN1 gene imparts a high risk of severe COVID-19 (odds ratio-6.214 (1.84-20.99) p = 0.003; 9.421 (2.019-43.957) p = 0.004), in additive inheritance model (adjusted and unadjusted, respectively).

Oscillometry-Defined Small Airway Dysfunction in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: The prevalence of small airway dysfunction (SAD) in patients with chronic obstructive pulmonary disease (COPD) across different ethnicities is poorly understood. This study aimed to estimate the prevalence of SAD in stable COPD patients. METHODS: We conducted a cross-sectional study of 196 consecutive stable COPD patients. We measured pre- and post-bronchodilator (BD) lung function and respiratory impedance. The severity of COPD and lung function abnormalities was graded in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SAD was defined as either difference in whole-breath resistance at 5 and 19 Hz > upper limit of normal or respiratory system reactance at 5 Hz < lower limit of normal. RESULTS: The cohort consisted of 95.9% men, with an average age of 66.3 years. The mean forced expiratory volume 1 second (FEV1) % predicted was 56.4%. The median COPD assessment test (CAT) scores were 14. The prevalence of post-BD SAD across the GOLD grades 1 to 4 was 14.3%, 51.1%, 91%, and 100%, respectively. The post-BD SAD and expiratory flow limitation at tidal breath (EFLT) were present in 62.8% (95% confidence interval [CI], 56.1 to 69.9) and 28.1% (95% CI, 21.9 to 34.2), respectively. COPD patients with SAD had higher CAT scores (15.5 vs. 12.8, p<0.01); poor lung function (FEV1% predicted 46.6% vs. 72.8%, p<0.01); lower diffusion capacity for CO (4.8 mmol/min/kPa vs. 5.6 mmol/min/kPa, p<0.01); hyperinflation (ratio of residual volume to total lung capacity % predicted: 159.7% vs. 129%, p<0.01), and shorter 6-minute walk distance (367.5 m vs. 390 m, p=0.02). CONCLUSION: SAD is present across all severities of COPD. The prevalence of SAD increases with disease severity. SAD is associated with poor lung function and higher symptom burden. Severe SAD is indicated by the presence of EFLT.

Exploring the Immunodominant Epitopes of SARS-CoV-2 Nucleocapsid Protein as Exposure Biomarker.

Background The nucleocapsid protein (N protein) of SARS-CoV-2 is undeniably a potent target for the development of diagnostic tools due to its abundant expression and lower immune evasion pressure compared to spike (S) protein. Methods Blood samples of active COVID-19 infections (n=71) and post-COVID-19 (n=11) were collected from a tertiary care hospital in India; pre-COVID-19 (n=12) sera samples served as controls. Real-time reverse transcriptase-PCR (rRT-PCR) confirmed pooled sera samples (n=5) were used with PEPperCHIP® SARS-CoV-2 Proteome Microarray (PEPperPRINT GmbH, Germany) to screen immunodominant epitopes of SARS-CoV-2. Highly immunodominant epitopes were then commercially synthesized and further validated for their immunoreactivity by dot-blot and ELISA. Results The lowest detectable concentration (LDC) of the N1 peptide in the dot-blot assay was 12.5 µg demonstrating it to be fairly immunoreactive compared to control sera. IgG titers against the contiguous peptide (N2: 156AIVLQLPQGTTLPKGFYAEGS176) was found to be significantly higher (p=0.018) in post-COVID-19 compared to pre-COVID-19 control sera. These results suggested that N2-specific IgG titers buildup over time as expected in post-COVID-19 sera samples, while a non-significant immunoreactivity of the N2 peptide was also observed in active-COVID-19 sera samples. However, there were no significant differences in the total IgG titers between active COVID-19 infections, post-COVID-19 and pre-COVID-19 controls. Conclusion The N2-specific IgG titers in post-COVID-19 samples demonstrated the potential of N protein as an exposure biomarker, particularly in sero-surveillance studies.

Influence of laboratory biomarkers on inflammatory indices for assessing severity progression in COVID-19 cases.

Background and Objective: This study explored the role of various laboratory biomarkers on inflammatory indices for predicting disease progression toward severity in COVID-19 patients. Methods: This retrospective study was conducted on 1233 adults confirmed for COVID-19. The participants were grouped undermild, moderate, and severe grade disease. Serum bio-inflammatory index (SBII) and systemic inflammatory index (SII) were calculated and correlated with disease severity. The study variables, including clinical details and laboratory variables, were analyzed for impact on the inflammatory indices and severity status using a sequential multiple regression model to determine the predictors for mortality. Receiver operating characteristics defined the cut-off values for severity. Results: Among the study population, 56.2%, 20.7%, and 23.1% were categorized as mild, moderate, and severe COVID-19 cases. Diabetes with hypertension was the most prevalent comorbid condition. The odds for males to have the severe form of the disease was 1.6 times (95% CI = 1.18-2.18, P = 0.002). The median (inter-quartile-range) of SBII was 549 (387.84-741.34) and SII was 2097.6 (1113.9-4153.73) in severe cases. Serum urea, electrolytes, gamma-glutamyl transferase, red-cell distribution width-to-hematocrit ratio, monocytopenia, and eosinopenia exhibited a significant influence on the SpO2, SBII, and SII. Both SBII (r = -0.582, P < 0.001) and SII (r = -0.52, P < 0.001) strongly correlated inversely with SpO2 values [Figures 3a and 3b]. More than 80% of individuals admitted with severe grade COVID-19 had values of more than 50th percentile of SBII and SII. The sensitivity and specificity of SBII at 343.67 for severity were 81.4% and 70.1%, respectively. SII exhibited 77.2% sensitivity and 70.8% specificity at 998.72. Conclusion: Serial monitoring of the routinely available biomarkers would provide considerable input regarding inflammatory status and severity progression in COVID-19.

18F-Labeled Fluoro-2-Deoxyglucose Positron Emission Tomography and Computed Tomography in a Large Pulmonary Sclerosing Pneumocytoma with Contralateral Lung Metastasis.

Pulmonary sclerosing pneumocytoma is an exceedingly rare neoplasm of the lung. These tumors are usually slow growing with a benign disease course but can easily be mistaken for carcinoid tumors or adenocarcinoma in cytology or histopathology specimens. Rare occurrences of metastases have been reported in the literature making 18F-labeled fluoro-2-deoxyglucose positron emission tomography and computed tomography useful for the evaluation of these tumors.

Left pulmonary aplasia with multiloculated effusion and pericardial defects in a young adult: a case report.

Pulmonary aplasia is a rare developmental lung anomaly with unknown etiology. Multiloculated effusion and pericardial defects are even less common with no cases reported up until now. Here, we report the first case of an unusual presentation of a 25-year-old female with recurrent cough for four months, who was diagnosed with left pulmonary aplasia with multiloculated effusion and partial pericardial defects, and who underwent uniportal thoracoscopic drainage and pleurectomy.

Detection of a Lophomonas, a rare pathogen in Bronchoalveolar lavage.

Lophomonas infection is an emerging parasitic disease-causing respiratory infection. Although common in immunocompromised patient, it has been observed also in some immunocompetent cases. We report the case of a 45-year-old male who presented with productive cough, fever, and chest pain, with marked eosinophilia and cavitary lesion in the X-ray chest. KOH preparation and acid-fast bacilli microscopy of bronchoalveolar lavage (BAL) were negative. Direct microscopic examination of BAL accidentally showed a large number of living Lophomonas species with the movement of flagella. Methylene blue and Giemsa staining showed the plume of flagella and the nucleus. The patient was managed conservatively with metronidazole and get cured. It was concluded that the patient presented with signs and symptoms of pneumonia must be evaluated for rare events also if the patient was not responding with typical management of pneumonia. We reported the first case of this rare entity in Chhattisgarh state in an immunocompetent young Indian male.

Obstructive sleep apnea and the effect of CPAP treatment on ischemia-modified albumin levels: a multi effect size meta-analysis with diagnostic test accuracy.

PURPOSE: A close association of oxidative stress (OS) and ischemia-modified albumin (IMA) with obstructive sleep apnea (OSA) has been reported in the literature, but the results on IMA are ambiguous. We conducted a meta-analysis to evaluate the association of IMA with OSA and the effect of continuous positive airway pressure (CPAP) therapy on IMA in patients with OSA. METHODS: Relevant studies were identified by searching PubMed and other databases in addition to manual searching of cross-references. Using random-effects model, the standardized mean differences (SMDs), pooled correlation coefficients and summary of diagnostic test accuracies were obtained with 95% confidence intervals (CIs). The meta-regression, sub-group and sensitivity analyses were performed to explore heterogeneity. The presence of publication bias was tested using funnel plot analysis followed by Begg's and Egger's tests for statistical signidicance. RESULTS: This meta-analysis finally included nine studies. When comparing with non-OSA controls, the OSA patients showed a significantly increased circulatory IMA levels (SMD = 1.15, p = 0.0001). And, this increase is even more pronounced in severe-OSA group as compared to mild-moderate OSA patients (SMD = 076, p = 0.0006). A decrease in post-CPAP treatment IMA was observed when compared with that of baseline values. Meta-analysis of correlations showed significant associations of IMA with polysomnographic parameters. The pooled diagnostic odds ratio and area under curve were 19.58 and 0.888 (Q* = 0.819), respectively. There was no evidence of publication bias for the association of IMA with OSA. CONCLUSION: This meta-analysis suggests that OSA is associated with significantly increased IMA levels which may indicate OS, ischemia and subclinical cardiovascular risk. In the diagnostic test accuracy meta-analysis, IMA showed good accuracy for OSA detection. However, further studies are required to establish its clinical utility.

Study the association of chronic obstructive pulmonary disease with early endothelial dysfunction and its impact on cardiovascular system by estimating urinary albumin creatinine ratio.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) attribute to systemic inflammation which is responsible for microalbuminuria reflecting endothelial dysfunction, could be a significant surrogate marker of potential cardiovascular morbidity. OBJECTIVE: The aim of our study was to find out the possible association of COPD with early cardiovascular changes in the form of renal endothelial dysfunction. SETTINGS AND DESIGN: Case-control, multi-group, cross-sectional hospital-based study was designed and conducted in the Department of Respiratory Medicine of BPS Government Medical College for Women, Khanpur Kalan, Sonipat, Haryana. SUBJECTS AND METHODS: The study included 150 subjects, comprising of three groups with each having 50 subjects: Group 1 - acute exacerbation of COPD, Group 2 - stable COPD patients, Group 3 - asymptomatic smokers. Pulmonary function test, urine albumin creatinine ratio (UACR) and brachio-ankle pulse wave velocity were measured in all the subjects. STATISTICAL ANALYSIS: Data were analyzed using SPSS ver 20 (IBM, USA) software. Continuous variables were compared by unpaired Student's t-test while correlation was measured by Pearson correlation test, P < 0.05 was considered statistically significant. RESULTS: The mean urine albumin creatinine ratio UACR value in acute exacerbation of COPD (283.30 mg/g; standard deviation [SD] ±871.98) was found significantly higher compare to control subjects (24.17 mg/g; SD ± 32.105;) P = 0.038. Besides this COPD patients with Type 2 respiratory failure having robust positive correlation in between UACR and arterial blood pH (r = 0.559; P = 0.030) while it was inverse and moderate with partial pressure of arterial oxygen (r = -0.470; P = 0.077). CONCLUSIONS: Acute state of COPD with or without Type 2 respiratory failure is having a significant impact on cardiovascular system in the form of early microvascular changes.