Application of a High-Content Screening Assay Utilizing Primary Human Lung Fibroblasts to Identify Antifibrotic Drugs for Rapid Repurposing in COVID-19 Patients.

Lung imaging and autopsy reports among COVID-19 patients show elevated lung scarring (fibrosis). Early data from COVID-19 patients as well as previous studies from severe acute respiratory syndrome, Middle East respiratory syndrome, and other respiratory disorders show that the extent of lung fibrosis is associated with a higher mortality, prolonged ventilator dependence, and poorer long-term health prognosis. Current treatments to halt or reverse lung fibrosis are limited; thus, the rapid development of effective antifibrotic therapies is a major global medical need that will continue far beyond the current COVID-19 pandemic. Reproducible fibrosis screening assays with high signal-to-noise ratios and disease-relevant readouts such as extracellular matrix (ECM) deposition (the hallmark of fibrosis) are integral to any antifibrotic therapeutic development. Therefore, we have established an automated high-throughput and high-content primary screening assay measuring transforming growth factor-ß (TGFß)-induced ECM deposition from primary human lung fibroblasts in a 384-well format. This assay combines longitudinal live cell imaging with multiparametric high-content analysis of ECM deposition. Using this assay, we have screened a library of 2743 small molecules representing approved drugs and late-stage clinical candidates. Confirmed hits were subsequently profiled through a suite of secondary lung fibroblast phenotypic screening assays quantifying cell differentiation, proliferation, migration, and apoptosis. In silico target prediction and pathway network analysis were applied to the confirmed hits. We anticipate this suite of assays and data analysis tools will aid the identification of new treatments to mitigate against lung fibrosis associated with COVID-19 and other fibrotic diseases.

Human rights, public health and COVID-19 in Canada.

Faced with the extraordinary global public health crisis of COVID-19, governments across Canada must decide, often with limited and imperfect evidence, how to implement measures to reduce its spread. Drawing on a health and human rights framework, this commentary explores several features of the Canadian response to date that raise human rights concerns. Our discussion focuses on criminal law, fines, data collection, and so-called snitch lines. We argue that the approach of governmental and public health authorities must be grounded in the best available scientific evidence and align with human rights standards. Our aim is to encourage dialogue within the public health community in Canada about the importance of human rights-based responses to COVID-19.

RéSUMé: Face à la crise de santé publique sans précédent que représente la COVID-19 à l'échelle mondiale, les gouvernements des provinces et territoires du Canada doivent décider, souvent en se fondant sur des preuves limitées et imparfaites, comment mettre en œuvre des mesures pour réduire sa propagation. En s'appuyant sur un cadre de travail relatif à la santé et aux droits de la personne, cette analyse explore plusieurs éléments de la réponse canadienne apportée à ce jour qui soulèvent des préoccupations en matière de droits de la personne. Notre analyse porte en particulier sur le droit criminel, les amendes, la collecte de données et ce qu'on appelle les « lignes de dénonciation ¼. Nous estimons que l'approche des autorités gouvernementales et de santé publique doit être fondée sur les preuves scientifiques disponibles les plus solides et s'aligner sur les normes en matière de droits de la personne. Nous avons pour objectif d'encourager le dialogue au sein de la communauté du secteur de la santé publique au Canada sur l'importance des réponses à la COVID-19 fondées sur les droits de la personne.