Does Raised Transaminases Predict Severity and Mortality in Patients with COVID 19?

Background: The most dreaded pandemic grappling world now, the Coronavirus Disease 2019 (COVID-19), chiefly involves the respiratory system; nevertheless, it is a multisystem disorder. Its involvement of the hepatic system is considerable; however, still emerging are its clinical implications and the effects on morbidity and mortality. Aim: The aim of this study is to report on the various aspects of its hepatic involvement by describing the alterations in tests of liver function and its significance in the disease outcome in a cohort of hospitalized COVID-19 patients at a tertiary center in northern India. Methods: This is a retrospective cohort study conducted in a tertiary-care hospital in northern India. All confirmed hospitalized COVID-19 cases aged 15 and above from Apr to Oct 2020 with no pre-existing liver disease were included. The primary endpoint was death at 28 days. Statistical analysis included descriptive analysis, sensitivity-specificity, and univariable and multivariable regression analysis as well as survival analysis. Results: A total of 708 patients with COVID-19 fulfilled the inclusion criteria included 561 (79.2%) males and 147 (20.8%) females. The median age was 49 (IQR = 25) years. Mild and moderate/severe disease were seen in 508 (71.8%) and 200 (28.2) patients, respectively. Serum bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were elevated in 6.92%, 69.91%, and 80.22% of patients, respectively. In univariable logistic regression, AST [odds ratio; OR 1.008 95% CI (1.005-1.012) per 1 IU/L increase] and ALT [OR 1.005 95% CI (1.002-1.007) per 1 IU/L increase] were significantly associated with the odds of moderate to severe disease but only AST was significant after adjustment to age, sex, and comorbidity [adjusted odds ratio; aOR 1.007 95% CI (1.003-1.011) per 1 IU/L increase]. Serum albumin was negatively associated with the odds of moderate to severe disease and remained significant in the adjusted model [aOR 0.217 95%CI (0.149-0.316) per 1 g/dL increase].Ninety-six patients succumbed to illness [case fatality rate; CFR 13.6%). In adjusted Cox Proportional-Hazards Model for mortality, AST [adjusted hazard ratio; aHR 1.002 95% CI (1.000-1.003) per 1 IU/L increase] and serum albumin [aHR 0.396 95% CI (0.285-0.549) per 1 g/dL increase] showed significant association with mortality. Conclusion: Liver function abnormalities are common in patients with COVID-19. In particular, AST and serum albumin levels are effective predictors of disease severity and mortality and can be used as markers of fatal disease in the management as well as prognostication of COVID-19.

Functional impairment in bronchiectasis: Spirometry parameters versus St. George's Respiratory Questionnaire scores: Any co-relation?

OBJECTIVES: Bronchiectasis is a common respiratory disease which has significant morbidity and mortality. Health-related quality of life scores are not routinely used for the assessment of bronchiectasis. The present study was undertaken with an aim to assess the clinical profile and functional impairment using spirometry in patients with bronchiectasis and to co-relate functional impairment with their St. George's Respiratory Questionnaire (SGRQ) score. METHODOLOGY: This was a cross-sectional study carried out on 102 patients of bronchiectasis. All patients were assessed for clinical profile, spirometry, and SGRQ scores. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC were measured and compared with SGRQ scores. Data analysis was done using SPSS version 20.0 and MS-Excel. RESULTS: Obstruction was found in 62.7% and significant bronchodilator reversibility was observed in 30.4%. All spirometry parameters individually and combined showed a negative co-relation which was stastically significant (P < 0.001). Best co-relation was with FEV1 r = -0.809; symptom score, r = -0.821; activity score, r= -0.849; impact score and r = -0.873 total score. FVC% versus symptoms score r = -0.735; activity score r = -0.729, impacts score r = -0.778; total score r = -0.792. FEV1/FVC versus symptoms score r = -0.227, activity score r = -0.278, impacts score r = -0.263, total score r = -0.274. CONCLUSION: SGRQ scores have shown good correlation with functional impairment. It can be used as a modality to evaluate health status of patient in resource constraint settings.

Ferritin and Hemoglobin as Predictors of Fatal Outcome in COVID-19: Two Sides of the Same Coin.

INTRODUCTION: Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have multisystemic involvement with hyperinflammation being a cardinal feature and deranged iron metabolism having a possible role. In this premise, we studied the prognostic value of two markers of iron metabolism ferritin and hemoglobin. METHODOLOGY: A retrospective-cohort study was carried out in a tertiary hospital in northern India involving 210 hospitalized COVID-19 patients aged 15-and above. Analysis was done for clinical profile, comorbidities and basic laboratory indices including ferritin-hemoglobin ratio (FHR) with primary end-point being in-hospital all-cause mortality. RESULTS: Median serum ferritin levels (640.00ng/mL vs 220.00ng/mL) were significantly higher among non-survivors as against survivors while median hemoglobin levels were significantly lower (12.12g/dL vs 13.73g/dL). Serum ferritin levels >400ng/mL (Sn 80%, Sp 70%) predicted mortality with high sensitivity and specificity. Notably, serum ferritin levels >400ng/mL (HR 11.075 [1.481-82.801]) and anemia, defined as a hemoglobin of <12g/dL for females and < 13g/dL for males and were significantly associated with the risk of mortality in a univariable Cox-proportional hazards regression. The median FHR was significantly higher among non-survivors compared to survivors (56.98 vs 17.17). FHR>31 (Sn 85% Sp 71.6%) was highly sensitive and specific for predicting mortality. The multivariable analysis indicated that FHR >31 remained an independent risk factor for mortality (HR 12.293 [3.147-48.028]). CONCLUSION: Ferritin-hemoglobin ratio (FHR), which encompasses into a single index, the effects of both elevated levels of ferritin and the severity of anemia, seems to perform particularly well as a prognostic marker and emerged as an independent risk factor for mortality in COVID-19 patients. Hyperferritinemia and anemia, both, are inexorably interlinked in addition to having a role, directly or indirectly in the disease pathophysiology. Ferritin and hemoglobin, hence should be seen as two sides of the same coin rather than as two discrete entities.

Vaccination status and COVID-19 related mortality: A hospital based cross sectional study.

BACKGROUND: Efficacy of vaccines studied in clinical trial settings are likely to be different from their effectiveness in a real-world scenario. Indian Armed Forces launched its vaccine drive against COVID-19 on 16 Jan 2021. This study evaluated the effect of vaccination on mortality amongst hospitalized COVID patients. METHODS: A cross sectional study was done on all admitted moderate to severe COVID-19 patients at a designated COVID hospital in New Delhi. The primary outcome assessed the association of being fully vaccinated with mortality. Unadjusted odds ratios (OR) (with 95% CI) was performed for each predictor. Logistic regression was used for multivariable analysis and adjusted odds ratios obtained. RESULTS: The 1168 patients included in the study had a male preponderance with a mean age of 54.6 (± 17.51) years. A total of 266 (23%) patients were partially vaccinated with COVISHIELD® and 184 (16%) were fully vaccinated. Overall, 518 (44.3%) patients had comorbidities and 332 (28.4%) died. Among those fully vaccinated, there was 12.5% (23/184) mortality while it was 31.45 % (309/984) among the unvaccinated (OR 0.3, 95% CI 0.2 to 0.5, p<0.0001). In a logistic regression model, complete vaccination status and younger age were found to be associated with survival. CONCLUSIONS: Vaccination with two doses of COVISHIELD® was associated with lower odds of mortality among hospitalized patients with moderate to severe COVID.

Clinical characteristics and clinical predictors of mortality in hospitalised patients of COVID 19 : An Indian study.

BACKGROUND: The rapid spread of the coronavirus disease 2019 (COVID-19) with high mortality rate necessitates disease characterization and accurate prognostication for prompt clinical decision-making. The aim of this study is to study clinical characteristics and predictors of mortality in hospitalized patients with COVID-19 in India. METHODS: Retrospective cohort study was conducted in a tertiary care hospital in northern India. All consecutive confirmed hospitalized COVID-19 cases aged 15 years and older from 13 Apr till 31 Aug 2020 are included. Primary end point was 30-day mortality. RESULTS: Of 1622 patients ,1536 cases were valid. Median age was 36 years, 88.3% were men and 58.1% were symptomatic. Fever (37.6%) was commonest presenting symptom. Dyspnea was reported by 15.4%. Primary hypertension (8.5%) was commonest comorbidity, followed by diabetes mellitus (6.7%). Mild, moderate, and severe hypoxemia were seen in 3.4%, 4.3%, and 0.8% respectively. Logistic regression showed greater odds of moderate/severe disease in patients with dyspnea, hypertension, Chronic Kidney Disease (CKD), and malignancy. Seventy six patients died (4.9%). In adjusted Cox proportional hazards model for mortality, patients with dyspnea (hazard ratio [HR]: 14.449 [5.043-41.402]), altered sensorium (HR: 2.762 [1.142-6.683]), Diabetes Mellitus (HR: 1.734 [1.001-3.009]), malignancy (HR:10.443 [4.396-24.805]) and Chronic Liver Disease (CLD) (HR: 14.432 [2.321-89.715]) had higher risk. Rising respiratory rate (HR: 1.098 [1.048-1.150]), falling oxygen saturation (HR: 1.057 per unit change 95% CI: 1.028-1.085) were significant predictors. CONCLUSION: Analysis suggests that age, dyspnea, and malignancy were associated with both severe disease and mortality. Diabetes Mellitus and Chronic Liver Disease were associated with increased the risk of fatal outcome. Simple clinical parameters such as respiratory rate and oxygen saturation are strong predictors and with other risk factors at admission can be effectively used to triage patients.

New-onset diabetes mellitus with COVID-19: Coincidence or cause.

Diabetes mellitus (DM) was noted as the commonest comorbidity in the coronavirus disease 2019 (COVID-19) which contributed to worse prognosis in these patients. In some cases, we also noted new-onset DM detected during hospitalization for symptomatic COVID disease. We describe three such cases, where the patients presented with severe symptomatic hyperglycemia and ketoacidosis in two and hyperosmolality in one of them. Antibody to GAD-65 was negative and varying degrees of C-peptide secretion was noted after recovery in them. There was no clinical or biochemical evidence of exocrine pancreatic involvement noted during acute presentation or after the recovery. This interesting phenomenon of coexisting DM in symptomatic COVID-19 requires further studies to differentiate between coincidence or causation.

Radiographical Spectrum of High-altitude Pulmonary Edema: A Pictorial Essay.

BACKGROUND: High-altitude pulmonary edema (HAPE) is a common cause of hospitalization in high altitude areas with significant morbidity. The clinical presentation of HAPE can overlap with a broad spectrum of cardiopulmonary diseases. Also, it is associated with varied radiological manifestations mimicking other conditions and often leading to unnecessary and inappropriate treatment. PATIENTS AND METHODS: The primary aim of the study was to study the various radiological manifestations of HAPE through real-world chest radiographs. We present six different chest X-ray patterns of HAPE as a pictorial assay, at initial presentation, and after the resolution of symptoms with supplemental oxygen therapy and bed rest alone. RESULTS: HAPE can present as bilateral symmetrical perihilar opacities, bilateral symmetrical diffuse opacities, unilateral diffuse opacities, bilateral asymmetrical focal opacities, and even lobar consolidation with lower zone or less commonly upper zonal predilection. These presentations can mimic many common conditions like heart failure, acute respiratory distress syndrome, pulmonary embolism, aspiration pneumonitis, pneumonia, malignancy, and tuberculosis. CONCLUSION: A holistic clinical-radiological correlation coupled with analysis of the temporal course can help high-altitude physicians in differentiating true HAPE from its mimics. HOW TO CITE THIS ARTICLE: Yanamandra U, Vardhan V, Saxena P, Singh P, Gupta A, Mulajkar D, et al. Radiographical Spectrum of High-altitude Pulmonary Edema: A Pictorial Essay. Indian J Crit Care Med 2021;25(6):668-674.

Management of primary pulmonary alveolar proteinosis: A multicentric experience.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar accumulation of surfactant material with reduced lung function and resulting hypoxemia. It is characterized by a variable clinical course, and whole lung lavage (WLL) is the standard treatment. Herein, we report our multicentric experience of management of primary PAP. MATERIALS AND METHODS: This retrospective study included patients with PAP managed at various armed forces respiratory centers from 2009 to 2019. The diagnosis of primary PAP was based on histopathologic confirmation on transbronchial lung biopsy or open lung biopsy and absence of causes of secondary PAP. We analyzed the response to WLL in these patients as well as the safety of the procedure. RESULTS: During the above-specified period, ten patients with a diagnosis of PAP were admitted to various armed forces respiratory centers. The median age of the patients was 34.5 years (range 23-59); there were nine males (90%). The mean duration (± standard deviation) of symptoms was 10.8 (±2.70) months. For management, WLL was done for eight patients with a median volume of 23.5 L (range 18-45) per patient. All the patients showed significant symptomatic response as well as improvement in physiological parameters with no major complications. The median follow-up of all patients was 18 (range 5-44) months. CONCLUSIONS: WLL is a safe, effective therapy in an experienced setting in patients with PAP and provides long-lasting benefits.

Comparative evaluation of effects of intrapleural block with adjuvants on analgesia and pulmonary function after intercostal drainage: A pilot study.

BACKGROUND: Inter-costal chest drain (ICD) used for varied thoracic pathologies causes continuous pain and irritation of the pleura, which limits respiratory efforts and impairs ventilatory function. Intrapleural block deposits local anaesthetic between the layers of pleura and may improve ventilatory function especially in non surgical patients. METHODS: Twenty eight ASA I-III patients treated with ICD, who could perform incentive spirometry, were included for study. They were randomized to 'Group C' (control group); 'Group B' (Bupivacaine); 'Group M' (Bupivacaine + Morphine) and 'Group D' (Bupivacaine + Dexmedetomidine). The drugs were administered via the ICD itself and clamped thereafter for 15 min. The success of the block was assessed by time for first analgesic demand, maximum inspiratory volume generated and Numerical Rating Scale score for pain; by patients. RESULTS: Effective analgesia was observed in Group B, M and D. Addition of an adjuvant significantly prolonged time for rescue analgesic demand. Patients who received local anaesthetic alone or with an adjuvant had significantly improved maximal inspiratory volume and required lesser rescue analgesics. No significant complications were observed in any group. Pain relief in post-surgical patients using intraplural block is masked by systemic analgesics. However its application in patients with ICD for non surgical indications was explored in this study and was found to improve patient comfort and ventilation. CONCLUSION: Intra-pleural blockade is safe and effective in relieving the constant pleural irritation and pain of ICD, thus enabling the patient to improve ventilatory effort and faster recovery of respiratory function.

Case series of Pulmonary Alveolar Microlithiasis from India.

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterised by calcific deposits in lung parenchyma. PAM being a progressive disease with dissociation between severity of clinical symptoms and radiological picture, it is often detected incidentally. Mutations in the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells are considered to be involved in the pathogenesis of PAM. The majority of the patients are diagnosed usually between the ages of 20 and 40 years, although paediatric PAM has also been reported. Diagnosis is confirmed by combination of radiological features, bronchial lavage and histopathological testing. At present, lung transplant is the only definitive treatment available. Though rare, the prevalence of PAM is worldwide. Till June 2018, 86 cases have been reported from India and 1042 cases have been reported worldwide. We report three cases from India, including a student, cement factory worker and a tailor, which will highlight the varied clinical and radiological presentations of this rare disease along with the response to treatment.

Hypertension and catecholamine levels in sleep apnoea.

BACKGROUND: Sleep-disordered breathing has been strongly associated with systemic hypertension. Increased sympathetic activity in sleep-disordered breathing may be responsible for this association. METHOD: In this sleep clinic-based study, 82 newly diagnosed patients of sleep-disordered breathing were evaluated for hypertension, and their plasma and urinary levels of catecholamines were measured. Catecholamine levels were then compared separately with the severity of sleep apnoea and blood pressure (BP). RESULTS: The prevalence of hypertension in the study population was 46.3%. The BP showed a strong and statistically significant correlation with apnoea-hypopnoea index (diastolic, r = 0.65, P < 0.001 and systolic, r = 0.60, P < 0.001) which was maintained even after the results were analysed separately for obese and non-obese subjects. Both plasma and urinary levels of catecholamines were greater in patients with severe sleep apnoea (compared to nonsevere cases) and in those with hypertension compared to normotensives. However, statistical significance was achieved only for urine catecholamines and not for plasma catechol-amines in both the cases. CONCLUSION: Hypertension is highly prevalent among Indian subjects with obstructive sleep apnoea. Catecholamine levels are significantly higher in hypertensive than in normotensive apnoeics and are also directly related to the severity of obstructive sleep apnoea. Twenty-four hour urinary catecholamine levels are more valid measures of sympathetic activity than spot plasma samples.