The impact of COVID-19 on rare metabolic patients and healthcare providers: results from two MetabERN surveys.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has caused disruption in all aspects of daily life, including the management and treatment of rare inherited metabolic disorders (IMDs). To perform a preliminary assessment of the incidence of COVID-19 in IMD patients and the impact of the coronavirus emergency on the rare metabolic community between March and April 2020, the European Reference Network for Hereditary Metabolic Diseases (MetabERN) has performed two surveys: one directed to patients' organizations (PO) and one directed to healthcare providers (HCPs). The COVID-19 incidence in the population of rare metabolic patients was lower than that of the general European population (72.9 × 100,000 vs. 117 × 100,000). However, patients experienced extensive disruption of care, with the majority of appointments and treatments cancelled, reduced, or postponed. Almost all HCPs (90%) were able to substitute face-to-face visits with telemedicine, about half of patients facing treatment changes switched from hospital to home therapy, and a quarter reported difficulties in getting their medicines. During the first weeks of emergency, when patients and families lacked relevant information, most HCPs contacted their patients to provide them with support and information. Since IMD patients require constant follow-up and treatment adjustments to control their disease and avoid degradation of their condition, the results of our surveys are relevant for national health systems in order to ensure appropriate care for IMD patients. They highlight strong links in an interconnected community of HCPs and PO, who are able to work quickly and effectively together to support and protect fragile persons during crisis. However, additional studies are needed to better appreciate the actual impact of COVID-19 on IMD patients' health and the mid- and long-term effects of the pandemic on their wellbeing.

RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells.

The cytokine interleukin (IL)-15, major histocompatibility complex (MHC) class I molecules and MHC class I chain-related proteins (MIC) A and B are involved in cellular immune responses to virus infections but their role in respiratory syncytial virus (RSV) infection has not been studied. We aimed to determine how RSV infection modulates IL-15 production, MHC class I and MICA expression in respiratory epithelial cells, the molecular pathways implicated in virus-induced IL-15 production and how interferon (IFN)-γ alters RSV-induced IL-15 production and MHC class I and MICA expression. We infected respiratory epithelial cell lines (A549 and BEAS-2B cells) and primary bronchial epithelial cells with RSV and measured production of IL-15, expression of MHC I and MICA and the role of the transcription factor nuclear factor (NF)-κB. We report here that RSV increases IL-15 in respiratory epithelial cells via virus replication and NF-κB-dependent mechanisms. Furthermore, RSV infection of epithelial cells upregulated cell surface expression of MICA and levels of soluble MICA. IFN-γ upregulated RSV induction of soluble IL-15 but inhibited induction of MICA. Upregulation of IL-15, MHC I and MICA are likely to be important mechanisms in activating immune responses to RSV by epithelial cells.