Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism.

BACKGROUND

Internationally, strategies focusing on reducing alcohol-related harms in homeless populations with severe alcohol use disorder (AUD) continue to gain acceptance, especially when conventional modalities focused on alcohol abstinence have been unsuccessful. One such strategy is the managed alcohol program (MAP), an alcohol harm reduction program managing consumption by providing eligible individuals with regular doses of alcohol as a part of a structured program, and often providing resources such as housing and other social services. Evidence to the role of MAPs for individuals with AUD, including how MAPs are developed and implemented, is growing. Yet there has been limited collective review of literature findings.

METHODS

We conducted a scoping review to answer, "What is being evaluated in studies of MAPs? What factors are associated with a successful MAP, from the perspective of client outcomes? What are the factors perceived as making them a good fit for clients and for communities?" We first conducted a systematic search in PubMed, Embase, PsycINFO, CINAHL, Sociological Abstracts, Social Services Abstracts, and Google Scholar. Next, we searched the gray literature (through focused Google and Ecosia searches) and references of included articles to identify additional studies. We also contacted experts to ensure relevant studies were not missed. All articles were independently screened and extracted.

RESULTS

We included 32 studies with four categories of findings related to: (1) client outcomes resulting from MAP participation, (2) client experience within a MAP; (3) feasibility and fit considerations in MAP development within a community; and (4) recommendations for implementation and evaluation. There were 38 established MAPs found, of which 9 were featured in the literature. The majority were located in Canada; additional research works out of Australia, Poland, the USA, and the UK evaluate potential feasibility and fit of a MAP.

CONCLUSIONS

The growing literature showcases several outcomes of interest, with increasing efforts aimed at systematic measures by which to determine the effectiveness and potential risks of MAP. Based on a harm reduction approach, MAPs offer a promising, targeted intervention for individuals with severe AUD and experiencing homelessness. Research designs that allow for longitudinal follow-up and evaluation of health- and housing-sensitive outcomes are recommended.