Objectives The main aim of this study was to find the prevalence of mortality among hospitalized COVID-19 infected patients and associated risk factors for death. Methods Three electronic databases including PubMed, Science Direct and Google Scholar were searched to identify relevant cohort studies of COVID-19 disease from January 1, 2020, to August 11, 2020. A random-effects model was used to calculate pooled prevalence rate (PR), risk ratio (RR) and 95% confidence interval (CI) for both effect measures. Cochrane chi-square test statistic Q, I 2 , and 2 tests were used to measure the presence of heterogeneity. Publication bias and sensitivity of the included studies were also tested. Results In this meta-analysis, a total of 58 studies with 122,191 patients were analyzed. The pooled prevalence rate of mortality among the hospitalized COVID-19 patients was 18.88%, 95% CI (16.46-21.30), p < 0.001. Highest mortality was found in Europe [PR 26.85%, 95% CI (19.41-34.29), p < 0.001] followed by North America [PR 21.47%, 95% CI (16.27-26.68), p < 0.001] and Asia [PR 14.83%, 95% CI (12.46-17.21), p < 0.001]. An significant association were found between mortality among COVID-19 infected patients and older age (> 65 years vs. < 65 years) [RR 3.59, 95% CI (1.87-6.90), p < 0.001], gender (male vs. female) [RR 1.63, 95% CI (1.43-1.87), p < 0.001], ICU admitted patients [RR 3.72, 95% CI (2.70-5.13), p < 0.001], obesity [RR 2.18, 95% CI (1.10-4.34), p < 0.05], hypertension [RR 2.08,95% CI (1.79-2.43) p < 0.001], diabetes [RR 1.87, 95% CI (1.23-2.84), p < 0.001], cardiovascular disease [RR 2.51, 95% CI (1.20-5.26), p < 0.05], and cancer [RR 2.31, 95% CI (1.80-2.97), p < 0.001]. In addition, significant association for high risk of mortality were also found for cerebrovascular disease, COPD, coronary heart disease, chronic renal disease, chronic liver disease, chronic lung disease and chronic kidney disease. Conclusion This meta-analysis revealed that the mortality rate among COVID-19 patients was highest in the European region and older age, gender, ICU patients, patients with comorbidity had a high risk for case fatality. Those findings would help the health care providers to reduce the mortality rate and combat this pandemic to save lives using limited resources.

Background: ß-thalassemia is one of the most common inherited blood disorders in the world and a major deterrent to the public health of Bangladesh. The management of thalassemia patients requires lifelong frequent blood transfusion and the available treatment options are unsatisfactory. A national policy on thalassemia prevention is mandatory in Bangladesh. However, precise and up-to-date information on the frequency of ß-thalassemia carriers are missing due to lack of accurate diagnostic approaches, limited access to information and absence of national screening program. This study aims to determine the nationwide carrier frequency of hemoglobin E (HbE) and βthalassemia and mutation spectrum among the carriers using molecular, hematological and biochemical methods. Methods: The study enrolled a total of 1877 individuals (60.1% male and 39.9% female) aged between 18 and 35 years. Total sample size and its division-wise breakdown were calculated in proportion to national and division-wise population. Venous blood was collected and subjected to CBC analysis and Hb-electrophoresis for each participant. Serum ferritin was measured to detect coexistence of iron deficiency anemia with thalassemia carrier. DNA-based High Resolution Melting (HRM) curve analysis was performed for confirmation of carrier status by mutation detection. Results: Of 11.89% (95% CI, 10.43-13.35) carriers of β-globin gene mutations, 8.68% (95% CI, 7.41-9.95) had HbE trait (ETT) and 2.24% (95% CI, 1.57-2.91) had beta-thalassemia trait (BTT). Among eight divisions, Rangpur had the highest carrier frequency of 27.1% (ETT-25%, BTT-2.1%), whereas Khulna had the lowest frequency of 4.2% (ETT-4.2% only). Moreover, αthalassemia, HbD trait, HbE disease, hereditary persistence of HbF were detected in 0.11, 0.16, 0.43 and 0.16% participants, respectively. HRM could identify two individuals with reported pathogenic mutations in both alleles who were erroneously interpreted as carriers by hematological indices. Finally, a total of nine different mutations including a novel mutation (c.151A > G) were detected in the β-globin gene. Conclusions: Since carrier frequency for both HbE and β-thalassemia is alarmingly high in Bangladesh, a nationwide awareness and prevention program should be made mandatory to halt the current deteriorating situations. Mutationbased confirmation is highly recommended for the inconclusive cases with conventional carrier screening methods to avoid any faulty detection of thalassemia carriers.

Liquid Chromatography tandem mass spectrometry (LC-MS/MS) is used for the diagnosis of more than 30 inborn errors of metabolisms (IEMs). Accurate and reliable diagnosis of IEMs by quantifying amino acids (AAs) and acylcarnitines (ACs) using LC-MS/MS systems depend on the establishment of age-specific cut-offs of the analytes. This study aimed to (1) determine the age-specific cut-off values of AAs and ACs in Bangladesh and (2) validate the LC-MS/MS method for diagnosis of the patients with IEMs. A total of 570 enrolled healthy participants were divided into 3 age groups, namely, (1) newborns (1-7 days), (2) 8 days–7 years, and (3) 8–17 years, to establish the age-specific cut-offs for AAs and ACs. Also, 273 suspected patients with IEMs were enrolled to evaluate the reliability of the established cut-off values. Quantitation of AAs and ACs was performed on an automated LC-MS/MS system using dried blood spot (DBS) cards. Then the specimens of the enrolled clinically suspected patients were analyzed by the established method. Nine patients came out as screening positive for different IEMs, including two borderline positive cases of medium-chain acyl-CoA dehydrogenase deficiency (MCAD). A second-tier test for confirmation of the screening positive cases was conducted by urinary metabolic profiling using gas chromatography- mass spectrometry (GC-MS). Out of 9 cases that came out as screening positive by LC-MS/MS, seven cases were confirmed by urinary GC-MS analysis including 3 cases with phenylketonuria, 1 with citrullinemia type II, 1 with methylmalonic acidemia, 1 with isovaleric acidemia and 1 with carnitine uptake defect. Two borderline positive cases with MCAD were found negative by urinary GC-MS analysis. In conclusion, along with establishment of a validated LC-MS/MS method for quantitation of AAs and ACs from the DBS cards, the study also demonstrates the presence of predominantly available IEMs in Bangladesh.