An epidemiological, strategic and response analysis of the COVID-19 pandemic in South Asia: a population-based observational study.

INTRODUCTION: South Asia has had a dynamic response to the ongoing COVID-19 pandemic. The overall burden and response have remained comparable across highly-burdened countries within the South Asian Region. METHODOLOGY: Using a population-based observational design, all eight South Asian countries were analyzed using a step-wise approach. Data were obtained from government websites and publicly-available repositories for population dynamics and key variables. RESULTS: South Asian countries have a younger average age of their population. Inequitable distribution of resources centered in urban metropolitan cities within South Asia is present. Certain densely populated regions in these countries have better testing and healthcare facilities that correlate with lower COVID-19 incidence per million populations. Trends of urban-rural disparities are unclear given the lack of clear reporting of the gaps within these regions. COVID-19 vaccination lag has become apparent in South Asian countries, with the expected time to complete the campaign being unfeasible as the COVID-19 pandemic progresses. CONCLUSION: With a redesigning of governance policies on preventing the rise of COVID-19 promptly, the relief on the healthcare system and healthcare workers will allow for adequate time to roll out vaccination campaigns with equitable distribution. Capacity expansion of public health within the Region is required to ensure a robust healthcare response to the ongoing pandemic and future infectious disease outbreaks.

Biochemical testing for the diagnosis of Wilson's disease: A systematic review.

BACKGROUND: Wilson's disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24-hour urinary copper, and ceruloplasmin using the Leipzig criteria. METHODS: Adhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4. RESULTS: Nine studies were included. The best practice evidence for 24-hour urinary copper test ranged from a cutoff value of 0.64-1.6 µmol/24 h (N = 268; sensitivity = 75.6%, specificity = 98.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2 µmol/g yielding a power of 96.4% sensitivity and 95.4% specificity (N = 1,150); however, the tried and tested 4 µmol/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2 g/L (N = 4,281; sensitivity = 77.1%-99%, specificity = 55.9%-82.8%). CONCLUSION: This paper provides a large-scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over- or under-estimation of the index tests.

CRISPR-Cas13a mediated targeting of hepatitis C virus internal-ribosomal entry site (IRES) as an effective antiviral strategy.

Hepatitis C is an inflammatory liver disease caused by the single-stranded RNA (ssRNA) hepatitis C virus (HCV). The genetic diversity of the virus and quasispecies produced during replication have resulted in viral resistance to direct-acting antivirals (DAAs) as well as impediments in vaccine development. The recent adaptation of CRISPR-Cas as an alternative antiviral approach has demonstrated degradation of viral nucleic acids in eukaryotes. In particular, the CRISPR-effector Cas13 enzyme has been shown to target ssRNA viruses effectively. In this work, we have employed Cas13a to knockdown HCV in mammalian cells. Using a computational screen, we identified several potential Cas13a target sites within highly conserved regions of the HCV internal ribosomal entry site (IRES). Our results demonstrate significant inhibition of HCV replication as well as translation in huh-7.5 cells with minimal effects on cell viability. These findings were validated using a multi-modality approach involving qRT-PCR, luciferase assay, and MTT cell viability assay. In conclusion, the CRISPR-Cas13a system efficiently targets HCV in vitro, suggesting its potential as a programmable therapeutic antiviral strategy.

Evolution of efficacious pangenotypic hepatitis C virus therapies.

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes. Subsequently, establishment of cell-based replicon systems enabled investigations into various stages of HCV life cycle including its entry, replication, translation, and assembly, as well as role of host proteins. Collectively, these approaches have facilitated identification of important molecules that are deemed essential for HCV life cycle. The expanded set of putative virus and host-encoded targets has brought us one step closer to developing robust strategies for efficacious, pangenotypic, and well-tolerated medicines against HCV. Herein, we provide an overview of the development of various classes of virus and host-directed therapies that are currently in use along with others that are undergoing clinical evaluation.