ABSTRACT
Background: Socially vulnerable populations were vastly affected by the COVID-19 pandemic. The pandemic significantly impacted Brazil, pressuring its healthcare system for several months, with high mortality rates, even among the youngest population. Cohort studies combining disease surveillance are essential for understanding virus circulation in the community, surrogates of protection, vaccine effectiveness, and demand for health resources. Methods: : Here, we present the protocol for a community-based prospective cohort study in the largest complex of favelas (slums) in Rio de Janeiro, Brazil (Complexo da Maré). The study participants are residents initially recruited during a massive vaccination campaign in the community. Five waves of data collection at approximately six-month intervals were planned. The first two waves have been completed at the time of writing this study protocol, and the third is underway. The protocol comprises interviews, blood sampling, and records linkage with secondary data to enrich the profiles of cohort participants and community information. We will describe COVID-19 seroprevalence, socio-demographic characteristics, and the burden of COVID-19, followed by estimating the association of socioeconomic factors and the burden of disease with seroprevalence. Discussion: The primary aims of the study are to assess COVID-19 clinical, epidemiological and genomic profiles and outcomes in residents from Maré, including vaccine effectiveness, surrogates of immune protection, virus transmission in households, and the overall burden of the pandemic.
ABSTRACT
Background: The remarkable ability of the liver to regenerate by proliferation of mature hepatocytes constitutes the first mechanism of repair commonly named the hepatocyte-driven regeneration. Yet, during chronic liver injury or acute severe hepatocyte death, proliferation of hepatocytes becomes exhausted. In these cases, alternative cholangiocyte-driven regeneration occurs during which cholangiocytes differentiate into healthy hepatocytes. Despite these two mechanisms of repair, end stage liver disease remains the 12th most common cause of death in the US, begging for therapeutic strategies to harness intrinsic mechanisms of regeneration. My lab investigates various strategies using nucleoside-modified mRNA complexed in lipid nanoparticles (mRNA-LNP) to harness hepatocyte-and cholangiocyte-driven liver repair to treat acute and chronic liver disease mouse models. Method(s): We recently pioneered mRNA-LNP as a technology to deliver regenerative factors to the liver for liver regeneration application, departing from the original protein replacement or immunization applications whose safety is widely validated with the current mRNA-based COVID-19 vaccines. Acute and chronic liver diseases were recapitulated in mice with the single dose of acetaminophen (APAP) overdose model and the choline-deficient ethioninesupplemented (CDE) diet, respectively. Mice were also injected with AAV8-Tbg-p21 prior to liver injury to mimic hepatocyte senescence. Result(s): We demonstrate that delivery via mRNA-LNP to the liver of the known key hepatocyte mitogen hepatocyte growth factor (HGF) and epidermal growth factor (EGF) enhances hepatocyte-driven repair by sharply reversing steatosis and accelerating restoration of liver function in the CDE chronic model, while accelerating liver regeneration in APAP acute model with rapid return to baseline serum ALT levels. Interestingly, the overlooked factor, growth hormone, delivered with mRNA-LNP significantly accelerates liver repair after APAP overdose. To harness cholangiocyte-driven repair, we delivered VEGFA in acute and chronic injured mouse livers. We found that VEGFA mRNA-LNP induces robust cholangiocyte conversion to hepatocytes, and importantly, reverts steatosis and fibrosis. Conclusion(s): Our study introduces mRNA-LNP as a potentially translatable safe therapeutic intervention to harness both hepatocyte-and cholangiocyte-driven liver regeneration to ultimately treat human acute and chronic liver diseases.
ABSTRACT
In this paper, we measure the effect of the 2020 COVID-19 pandemic wave at the national and subnational levels in selected Latin American countries that were most affected: Brazil, Chile, Ecuador, Guatemala, Mexico, and Peru. We used publicly available monthly mortality data to measure the impacts of the pandemic using excess mortality for each country and its regions. We compare the mortality, at national and regional levels, in 2020 to the mortality levels of recent trends and provide estimates of the impact of mortality on life expectancy at birth. Our findings indicate that from April 2020 on, mortality exceeded its usual monthly levels in multiple areas of each country. In Mexico and Peru, excess mortality was spreading through many areas by the end of the second half of 2020. To a lesser extent, we observed a similar pattern in Brazil, Chile, and Ecuador. We also found that as the pandemic progressed, excess mortality became more visible in areas with poorer socioeconomic and sanitary conditions. This excess mortality has reduced life expectancy across these countries by 2-10 years. Despite the lack of reliable information on COVID-19 mortality, excess mortality is a useful indicator for measuring the effects of the coronavirus pandemic, especially in the context of Latin American countries, where there is still a lack of good information on causes of death in their vital registration systems. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s41118-021-00139-1.