SARS-CoV-2 Neuronal Invasion and Complications: Potential Mechanisms and Therapeutic Approaches.

Clinical reports suggest that the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) has not only taken millions of lives, but has also created a major crisis of neurologic complications that persist even after recovery from the disease. Autopsies of patients confirm the presence of the coronaviruses in the CNS, especially in the brain. The invasion and transmission of SARS-CoV-2 in the CNS is not clearly defined, but, because the endocytic pathway has become an important target for the development of therapeutic strategies for COVID-19, it is necessary to understand endocytic processes in the CNS. In addition, mitochondria and mechanistic target of rapamycin (mTOR) signaling pathways play a critical role in the antiviral immune response, and may also be critical for endocytic activity. Furthermore, dysfunctions of mitochondria and mTOR signaling pathways have been associated with some high-risk conditions such as diabetes and immunodeficiency for developing severe complications observed in COVID-19 patients. However, the role of these pathways in SARS-CoV-2 infection and spread are largely unknown. In this review, we discuss the potential mechanisms of SARS-CoV-2 entry into the CNS and how mitochondria and mTOR pathways might regulate endocytic vesicle-mitochondria interactions and dynamics during SARS-CoV-2 infection. The mechanisms that plausibly account for severe neurologic complications with COVID-19 and potential treatments with Food and Drug Administration-approved drugs targeting mitochondria and the mTOR pathways are also addressed.

The role of emptying services in provision of safely managed sanitation: A classification and quantification of the needs of LMICs.

Classifications for onsite sanitation in terms of facility type (septic tanks, pit latrines) exist, but connecting these facilities to the wider sanitation value chain via improved containment, emptying, and collection has not been well explored. Using existing Joint Monitoring Programme facility classifications and secondary data on piped water access, a Service Typology was developed to classify and quantify the primary emptying service needs of household level onsite sanitation facilities. Facilities in six Sustainable Development Goal (SDG) regions were classified as Emptiable (faecal sludge can be removed either via Mechanized or Non-Mechanized means) or Unemptiable. Of the 722 million household level sanitation facilities assessed in these regions, 32% were found to be emptiable via Mechanized means, 50% via Non-Mechanized means and 18% were found to be Unemptiable pits. The volume (by number of facilities) and density (as a proportion of the full population) of each service type were estimated by SDG region and by country. Results from this study provide background data on the role of emptying sanitation facilities in achieving SDG6, and can be incorporated into investment priorities, policy framing, technology development, infrastructure development, and targeted behaviour change strategies.