Mechanisms by which cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection

Background: People with cystic fibrosis (PwCF) have chronic, pronounced respiratory damage and have been considered among those at highest risk for serious harm from SARS-CoV-2. Numerous clinical studies have reported that individuals with CF in North America and Europe, although highly susceptible to COVID-19, do not have mortality levels that exceed those of the general population. Method(s): To understand features that might influence lethality of COVID- 19 in PwCF, we tested potential relationships between CFTR and viral pathogenesis. As one approach to evaluate impact of CF transmembrane conductance regulator (CFTR) on COVID-19 severity, independent sets of blood samples fromvirally infected individualswere genotyped. Bloodwas obtained from 424 U.S. patients hospitalized with severe COVID-19 and a much larger European cohort of 7147 healthy individuals and 2587 individuals with severe COVID-19. Deoxyribonucleic acid in both studies was probed for the F508del variant. In other experiments, we investigated the possibility that lack of CFTR might alter viral binding and propagation. We used human bronchial epithelial cell (HBEC) monolayers from individuals without functional CFTR for this purpose. Finally, we examined effects of CF airway secretions and features such as viscosity, pH, and protease/anti-protease imbalance during SARS-CoV-2 infection. Result(s): We found no evidence of a relationship between deficient CFTR function (based on carrier status for the severe F508del defect) and clinical outcomes from COVID-19. In addition, viral propagation studies using airway epithelial monolayers (a model that reproduces many aspects of in vivo tissue biology) were not influenced by homozygous absence of CFTR. We show that levels of angiotensin converting enzyme-2 receptor messenger ribonucleic acid (mRNA) appear normal in CF primary epithelium, whereas transmembrane serine protease 2 mRNA is variable but lower ( p < 0.001) in a manner that correlates with viral infectivity (R2 = 0.76). Dependence of viral proliferation on features of CF mucosal fluid-including pH (viral replication optimum at pH 7-7.5), viscosity (diminished propagation in highly viscous apical media), and protease/ anti-protease imbalancewere identified as likely contributors to efficiency of SARS-CoV-2 replication and pathogenesis. Conclusion(s): These findings using patient data, CF and non-CF primary airway epithelia, and CF airway secretions fail to demonstrate a causal relationship between loss of CFTR and susceptibility to severe COVID-19. Notwithstanding the caveat that addition of virus in small buffer volumes disrupts airway surface liquid depth and composition, our findings also argue against a role for CFTR during acute infection of airway cells in vitro. On the other hand, chronic disruption of periciliary liquid, diminished pH, altered protease/anti-protease homeostasis, and increased fluid viscosity (sequelae that occur in CF lungs) were implicated as contributors to impaired SARS-CoV-2 propagation. Such studies provide a basis for future work to test relationships between CFTR and severity of COVID-19. Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

COVID-19 related stigma and health-protective behaviours among adolescents in the Netherlands: An explorative study.

The COVID-19 pandemic has forced many governments to impose social distancing measures upon its citizens, including in the Netherlands. Motivating adolescents to adhere to measures such as social distancing can be challenging, since adolescents are relatively more affected by them, while experiencing virtually no personal health benefit. In addition, the COVID-19 pandemic seems to impact the social environment of adolescents in schools, as some media sources have reported bullying and stigmatisation of students with an Asian appearance. This study aims to explore the experiences of adolescents regarding their Health-Protective Behaviour (HPB), as well as the prevalence and expression of stigma towards ethnic minorities within the context of the first wave of COVID-19 pandemic. We performed a cross-sectional mixed-methods study, including two independent online questionnaires. An adapted version of the "HPB" questionnaire (n = 528) and the "Measure of Disease-Related Stigma (MDRS)" questionnaire (n = 380), were administered to Dutch adolescents of 10-16 years old, attending primary or secondary school. Furthermore, 15 interviews were held with eight male and seven female adolescents. All data collection took place between March 17 and April 20, 2020. Results show that adolescents perceive COVID-19 as a threat to other peoples' health, rather than their own, and report adherence to public health measures in the interest of older and more vulnerable members of their community. We found no convincing evidence for widespread misinformation or stigmatising of certain ethnic groups among adolescents related to COVID-19 during this study. Participants acknowledged such behaviour happened in the early stages of the pandemic, before this study was initiated. Adolescents are a vital group for public health researchers to engage with during a pandemic, even when reaching them can be challenging.

Mitigating the COVID-19 pandemic in India: an in-depth exploration of challenges and opportunities for three vulnerable population groups

Purpose: The COVID-19 pandemic is certain to have an unprecedented impact on the global population, but marginalized and vulnerable groups in low-income countries (LICs) are predicted to carry the largest burden. This study focuses on the implications of COVID-19-related measures on three population groups in India, including (1) migrant laborers (of which a majority come from Scheduled Castes (SCs) and Scheduled Tribes (STs), as well as Other Backward Classes (OBCs)), (2) children from low-income families and, (3) refugees and internally displaced persons (IDPs). Design/methodology/approach: This study adopts a sequential mixed-method research design. A desk-based study of a selection of government reports was undertaken on the COVID-19-related mitigation measures. The desk study was followed by in-depth interviews with purposively recruited high-ranking experts in specific sectors of policy implementation and service delivery across the country. Findings: The outcomes of this study shed light on (1) the most urgent needs that need to be addressed per population group, (2) the variety of state-level responses as well as best practices observed to deal with mitigation issues and (3) opportunities for quick relief as well as more long-term solutions. Practical implications: The COVID-19 pandemic has not only reduced people's means of maintaining a livelihood but has simultaneously revealed some of India's long-standing problems with infrastructure and resource distribution in a range of sectors, including nutrition and health, education, etc. There is an urgent need to construct effective pathways to trace and respond to those people who are desolate, and to learn from – and support – good practices at the grassroot level. Originality/value: The current study contributes to the discussion on how inclusive public health might be reached. © 2021, Joe Thomas, Emma Emily de Wit, R.K. Radhakrishnan, Nupur Kulkarni and Joske G.F. Bunders-Aelen.