GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection.

RATIONALE: Severe viral respiratory infections are often characterised by extensive myeloid cell infiltration and activation and persistent lung tissue injury. However, the immunological mechanisms driving excessive inflammation in the lung remain poorly understood. OBJECTIVES: To identify the mechanisms that drive immune cell recruitment in the lung during viral respiratory infections and identify novel drug targets to reduce inflammation and disease severity. METHODS: Preclinical murine models of influenza virus and severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. RESULTS: Oxidised cholesterols and the oxysterol-sensing receptor GPR183 were identified as drivers of monocyte-macrophage infiltration to the lung during influenza virus (IAV) and SARS-CoV-2 infection. Both IAV and SARS-CoV-2 infection upregulated the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) in the lung, resulting in local production of the oxidised cholesterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC). Loss-of-function mutation of GPR183, or treatment with a GPR183 antagonist, reduced macrophage infiltration and inflammatory cytokine production in the lungs of IAV- or SARS-CoV-2-infected mice. The GPR183 antagonist significantly attenuated the severity of SARS-CoV-2 infection and viral loads. Analysis of single cell RNASeq data on bronchoalveolar lavage samples from healthy controls and COVID-19 patients with moderate and severe disease revealed that CH25H, CYP7B1 and GPR183 are significantly upregulated in macrophages during COVID-19. CONCLUSION: This study demonstrates that oxysterols drive inflammation in the lung via GPR183 and provides the first preclinical evidence for therapeutic benefit of targeting GPR183 during severe viral respiratory infections.

Zooming into the COVID Era Together.

The pre-clinical medical school curriculum provides students with extraordinary experiences in preparation to become physicians. However, it was not originally designed to be delivered remotely. The COVID-19 pandemic promptly threw the medical education process into unforeseen circumstances. A model of student-faculty collaboration created to address new challenges and implement practical solutions rapidly is presented. This model was used effectively to respond to pre-clinical educational interruptions that were imposed by the COVID-19 pandemic and maintain high-quality training. Our experience provides valuable insights and lessons learned that can be applied to the ongoing pandemic response and to future educational challenges.

Zooming into the COVID Era Together

The pre-clinical medical school curriculum provides students with extraordinary experiences in preparation to become physicians. However, it was not originally designed to be delivered remotely. The COVID-19 pandemic promptly threw the medical education process into unforeseen circumstances. A model of student–faculty collaboration created to address new challenges and implement practical solutions rapidly is presented. This model was used effectively to respond to pre-clinical educational interruptions that were imposed by the COVID-19 pandemic and maintain high-quality training. Our experience provides valuable insights and lessons learned that can be applied to the ongoing pandemic response and to future educational challenges.

Addressing backlogs and managing waiting lists during and beyond the COVID-19 pandemic

In order to restore services to pre-pandemic levels and catch up on care, we need to understand and act on what we have learned from the pandemic, including investing in the health workforce, increasing funding for the health infrastructure of the future, and maintaining the innovative forms of service delivery that proved useful in reaching out to key groups affected by the pandemic. This brief is a valuable resource for policy-makers seeking to understand the extent of disruption to health services caused by COVID-19, the reasons behind this, and what different countries are doing in response. Its aim is to provide options to reduce service backlogs for those who are addressing this challenge in their national contexts.

Addressing backlogs and managing waiting lists during and beyond the COVID-19 pandemic

In order to restore services to pre-pandemic levels and catch up on care, we need to understand and act on what we have learned from the pandemic, including investing in the health workforce, increasing funding for the health infrastructure of the future, and maintaining the innovative forms of service delivery that proved useful in reaching out to key groups affected by the pandemic. This brief is a valuable resource for policy-makers seeking to understand the extent of disruption to health services caused by COVID-19, the reasons behind this, and what different countries are doing in response. Its aim is to provide options to reduce service backlogs for those who are addressing this challenge in their national contexts.

COVID-19 y trabajo informal: evidencia de once ciudades

Resumen Se presentan las conclusiones de un estudio dirigido por la red Mujeres en Empleo Informal: Globalizando y Organizando (WIEGO), en el que se investigan las repercusiones de la crisis de la COVID-19 en diferentes grupos de personas trabajadoras informales y en sus hogares en términos de empleo, ingresos, alimentación y hambre, cuidado y otras responsabilidades domésticas, así como las estrategias de afrontamiento de estas personas. Se comparan los roles de los gobiernos y de las organizaciones de personas trabajadoras informales en la prestación de diversas ayudas. Basándose en las reivindicaciones de estas personas, se plantean principios rectores para mejorar su situación en el futuro.

COVID-19 et travail informel: les enseignements d'une étude sur la situation dans onze grandes villes

Résumé Les auteurs présentent les conclusions d'une étude dirigée par le réseau Femmes dans l'emploi informel: globalisation et organisation (WIEGO) sur les effets de la crise du COVID-19 sur les travailleurs informels. L'analyse porte sur quatre professions et onze grandes villes de cinq régions. Il y est question du travail et des revenus, de l'accès à l'alimentation et de la faim, des responsabilités familiales et domestiques, ainsi que des stratégies d'adaptation des ménages. Les auteurs évoquent également les mesures de soutien proposées par les gouvernements et les organisations de travailleurs informels. Enfin, ils énoncent une série de principes devant guider l'action en faveur de ce groupe.

COVID-19 and informal work: Evidence from 11 cities

This article presents the findings of a study in 11 cities across five geographic regions on the impacts of the COVID-19 crisis on different groups of informal workers and their households. Four domains of impact are detailed: impact on work and income, food and hunger, care and other household responsibilities and on the coping strategies of informal workers households. The article also compares the role of government and of organizations of informal workers in providing relief and other support to informal workers and considers worker demands for a better deal for informal workers going forward.

Providing health services effectively during the first wave of COVID-19: A cross-country comparison on planning services, managing cases, and maintaining essential services.

The COVID-19 pandemic triggered abrupt challenges for health care providers, requiring them to simultaneously plan for and manage a rise of COVID-19 cases while maintaining essential health services. Since March 2020, the COVID-19 Health System Response Monitor, a joint initiative of the European Observatory on Health Systems and Policies, the WHO Regional Office for Europe, and the European Commission, has documented country responses to COVID-19 using a structured template which includes a section on provision of care. Using the information available on the platform, this paper analyzes how countries planned services for potential surge capacity, designed patient flows ensuring separation between COVID-19 and non-COVID-19 patients, and maintained routine services in both hospital and ambulatory settings. Despite very real differences in the organization of health and care services, there were many similarities in country responses. These include transitioning the management of COVID-19 mild cases from hospitals to outpatient settings, increasing the use of remote consultations, and cancelling or postponing non-urgent services during the height of the first wave. In the immediate future, countries will have to continue balancing care for COVID-19 and non-COVID-19 patients to minimize adverse health outcomes, ideally with supporting guidelines and COVID-19-specific care zones. Looking forward, policymakers will have to consider whether strategies adopted during the COVID-19 pandemic will become permanent features of care provision.