The impact on ambient air pollution and asthma-related admissions of COVID-19 transport restrictions : Caitriona Kelly

Exposure to air pollution is a known risk factor for asthma exacerbations, emergency attendances and hospitalisations. In Europe, the main source of air pollution is the transport industry, and so the COVID-19 transport restrictions provided an opportunity to examine if reduction in traffic had a demonstrable impact on ambient air quality and asthma-related admissions. Routinely collected data was used to conduct a retrospective population cohort study. The Environmental Protection Agency provided daily nitrogen dioxide (NO2) and particulate matter (PM) concentrations for Dublin, and all asthma-related admissions were collected from the Hospital In-Patient Enquiry system. The two years prior to the pandemic were compared with the period of transport restrictions (from March 2020). During the period of restrictions, there was a significant reduction in the mean number of daily asthma admissions (2.8 v 4.5 admissions p < 0.001). There was also a significant decrease in mean daily concentrations in two pollutants: NO2 (16.7 v 24.0µg/m3 p < 0.001) and PM2.5 (7.8 v 8.9µg/m3 p = 0.002). Only NO2 had a statistically significant correlation with asthma admissions (r = 0.132 p < 0.001). Transport restrictions introduced to mitigate against COVID-19 led to improvements in air quality, as seen by the reductions in pollutant concentrations. Previously described associations between pollutants and asthma, would suggest that these improvements in air quality contributed to the reduction in asthma admissions. Whereas the primary source of NO2 is transport emissions, PM is made up of particles from multiple sources, which likely explains the lack of correlation between asthma admissions and PM. Public Health need to advocate for transport policies which can improve air quality, and as a result, public health. Key messages Poor air quality poses a significant health challenge requiring public health input and advocacy. Reducing vehicle traffic can improve air quality which would have a positive impact on public health.

Ambient air pollutant concentrations and asthma-related hospital admissions during COVID-19 transport restrictions.

OBJECTIVES: Exposure to air pollution is a known risk factor for asthma exacerbations and hospitalisations. This study aimed to identify if COVID-19 transport restrictions led to improvements in air quality in Dublin and if this had an impact on asthma-related hospital admissions. STUDY DESIGN: This was a population-based retrospective cohort study. METHODS: Daily concentration levels of particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) were obtained from the Environmental Protection Agency (EPA). The Hospital In-Patient Enquiry (HIPE) system provided the daily number of asthma-related hospital admissions in Dublin. The figures for 2018-2019 were compared with the period of transport restrictions (from March 2020). RESULTS: During the period of transport restrictions, there was a significant decrease in mean daily concentrations in both PM2.5 (8.9 vs 7.8 µg/m3, P = 0.002) and NO2 (24.0 vs 16.7 µg/m3, P < 0.001). There was also a significant reduction in the mean number of daily asthma admissions (4.5 vs 2.8 admissions, P < 0.001). Only NO2 showed a statistically significant correlation with asthma admissions (r = 0.132, P < 0.001). CONCLUSION: Transport restrictions introduced to mitigate against COVID-19 led to lower pollutant levels and improved air quality. Previously described associations between pollutants and asthma would indicate that these improvements in air quality contributed to the reduction in asthma-related admissions. The complex nature of PM is the likely explanation for the lack of correlation between its concentration and asthma admissions, unlike NO2 whose primary source is vehicular emissions. Public Health needs to advocate for transport policies, which can improve air quality and hence improve human health.

Cybord-Dara in Newly Diagnosed Transplant-Eligible Multiple Myeloma: Follow up Results from the 16-Bcni-001/Ctrial-IE 16-02 Study Show High Rates of MRD Negativity at End of Treatment

The anti-CD38 monoclonal antibody Daratumumab has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM), improving progression free survival and overall survival in several phase 3 studies. We conducted a phase 1b study of intravenous Daratumumab (16 mg/kg) with weekly subcutaneous bortezomib (1.3-1.5 mg/m 2 ), cyclophosphamide (150-300 mg/m 2), and dexamethasone (40 mg) (CyBorD-DARA) as induction before autologous stem cell transplantation (ASCT), followed by CyBorD-DARA consolidation (2 cycles) and monthly DARA +/- bortezomib (in high-risk disease) maintenance for 24 months. We hypothesized that the addition of cyclophosphamide could lead to enhanced antibody dependent cellular phagocytosis (ADCP). This trial was registered at www.clinicaltrials.gov as NCT02955810. We previously reported the initial results of this study. 1. In addition to a favourable safety profile we observed promising anti-MM activity with 10 of 13 patients (77%) in whom assessment was possible achieving measurable residual disease (MRD) negativity at a sensitivity of 10 -5 by next generation sequencing (NGS) after ASCT. We now report the results at EOT, with a focus on MRD. Eligible patients were ≤70 years of age with untreated transplant-eligible MM. 18 patients were enrolled. Median age was 56.5 years (range, 32-66 years), 61% were male and 94% of patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively. 29% of patients had high-risk genetic features by fluorescent in situ hybridisation (FISH) or gene expression profiling, including 17p deletion in 12% and t(4;14) and t(14;16) in 6% each. On an ITT basis, the rates of very good partial remission or better (≥VGPR) after ASCT, consolidation and at end of treatment (EOT) (after completion of 24 months of DARA) were 94%, 94% and 81% respectively, and rates of complete response or better (≥CR) were 50%, 63% and 63% respectively. Measurable residual disease (MRD) assessment was possible in 13 patients after induction, ASCT and consolidation, and 10 at EOT. Sustained MRD negativity (ie. MRD negativity after ASCT, consolidation and at EOT) to a level of 10 -5 by NGS was achieved in 33% (ITT). Of 13 patients who remained on study at EOT in VGPR or better, 54% were MRD negative (MRD was unavailable in 23%). 7 patients were MRD negative after both ASCT and consolidation. Of these patients, all evaluable at EOT(6/7) remained MRD negative, with 1 patient unable to undergo MRD assessment due to the COVID-19 pandemic, but remaining in CR. Nausea and diarrhoea occurred in 89% of patients, but were mostly grade 1-2 (Grade ≥3 nausea 17%;diarrhoea 6%). Neutropenia occurred in 44% (Grade ≥3 17%), anaemia in 39% (Grade ≥3 22%), and thrombocytopenia in 33% (Grade ≥3 22%). The rate of neutropenic sepsis was 11%. Infusion-related reactions occurred in 50% (Grade ≥3 6%) and peripheral neuropathy occurred in 33% (Grade ≥3 0%) The most commonly reported serious adverse event (SAE) was sepsis in 22%. One patient developed abnormal liver function tests leading to discontinuation from the trial. CyBorD-DARA induction, consolidation and DARA-maintenance is an effective and well-tolerated IMiD free regimen in transplant-eligible patients with MM. MRD negativity at a level of > 10 -5 after ASCT and consolidation may be predictive of sustained MRD negativity at EOT. References: 1. Naicker SD, et al. Cyclophosphamide alters the tumor cell secretome to potentiate the anti-myeloma activity of daratumumab through augmentation of macrophage-mediated antibody dependent cellular phagocytosis. Oncoimmunology. 2021 Jan 25;10(1):1859263. doi: 10.1080/2162402X.2020.1859263. PMID: 33552684;PMCID: PMC7849715. 2. O'Dwyer M, et al. CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study. Blood Adv. 2019 Jun 25;3(12):1815-1825. doi: 10.1182/bloodadvances.2019000010. PMID: 31201169;PMCI : PMC6595251. Disclosures: O'Dwyer: ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees;Janssen: Consultancy;Bristol Myers Squibb: Research Funding. Quinn: Takeda: Honoraria. Szegezdi: ONK Therapeutics: Research Funding.

Gender and Crises in European Economic Governance: Is this Time Different?*

There is now a significant literature engaging with questions around gender and economic governance in the European Union. This builds upon research that demonstrates the gendered nature of the economy, and the gendered impacts of policy interventions. This paper draws on that research to develop an account of the gendered nature of the EU's crisis response, moving from analysis of the response to the Global Financial Crisis to some prelimary discussions of the EU's economic response to the COVID-19 pandemic. The paper shows how at each stage policies generate gendered consequences, and are built upon gendered assumptions about society and the economy. This paper therefore connects the feminist literature on the European Economic Governance to debates on the Covid-19 response, using a focus on gender and gender equality to examine key continuities between the crisis fighting of the Global Financial crisis to the establishment of the Next Generation EU fund.

Impact of COVID-19 Lockdown Restrictions: Ambient NO2 and Asthma Hospital Admissions

Aim The World Health Organization (WHO) declared the COVID-19 pandemic a global health emergency. Many countries of the world, including Ireland, closed their borders and imposed nationwide lockdown. During this period, all major anthropogenic transport activities, which contribute to atmospheric pollution, were restricted. The current study examines the impact of the transport restrictions on ambient nitrogen dioxide (NO2) concentrations and hospital admissions for asthma across Ireland. Methods This is a retrospective population-based cohort study. National ambient air quality monitoring network data were analysed to investigation variations in NO2 concentrations. Asthma hospital admissions data were collected from the HSE Hospital In-patient Enquiry (HIPE) for Cork, Dublin, and Meath. Results During the period of transport restrictions, there were reductions in the annual mean NO2 for Cork, Dublin and Meath (i.e. 12µg/m3 to 11µg/m3 (p = 1);25µg/m3 to 17µg/m3 (p < 0.001);and 23µg/m3 to 21µg/m3 (p = 1)). Reductions in asthma hospital admissions were also observed. Among the 8,471 patient episodes included in this study, the mean [SD] age at admission was 47.2[22.9] years;61% were female (n=5,134);mean [SD] length of stay was 4.9[10.9] days. Conclusion The findings of this study provide an opportunity to explore the impact of NO2 emissions for Cork, Dublin and Meath on asthma hospital admissions, in order to improve air quality modelling and policy development of management of asthma.

COVID-19 transport restrictions in Ireland: impact on air quality and respiratory hospital admissions.

AIM: Exposure to poor air quality is a well-established factor for exacerbation of respiratory system diseases (RSDs); whether air pollutants are a cause of the development of RSD, however, remains unclear. This study aimed to examine the relationship between COVID-19 transport restrictions and hospital admissions because of RSD in Dublin city and county for 2020. STUDY DESIGN: This was a retrospective population-based cohort. METHODS: Admission data were collected from the Health Service Executive Hospital In-patient Enquiry. Daily count of hospital admissions with Dublin city and county address with primary diagnosis of RSD was performed. The daily air nitrogen dioxide (NO2) data were obtained from the Environmental Protection Agency (EPA). RESULTS: During the period of transport restrictions, there was a reduction in the annual mean NO2 from 25 µg/m3 to 17 µg/m3 (P < 0.001), and decreases in hospital admissions for RSD were observed. Among the 9934 patient episodes included in this study, the mean age at admission was 61.5 years, 57.8% were female (n = 5744), and mean (standard deviation) length of stay was 7.5 (13.52) days. CONCLUSION: This study, using routinely gathered data, suggests that decreases in ambient NO2 as related to COVID-19 transport restrictions were significantly associated with lower asthma and chronic obstructive pulmonary disease admissions.

Extensive pneumatosis intestinalis and portal venous gas mimicking mesenteric ischaemia in a patient with SARS-CoV-2.

We present the case of a critically ill 47-year-old man diagnosed with SARS-CoV-2 (COVID-19) who developed extensive pneumatosis intestinalis and portal venous gas in conjunction with an acute abdomen during the recovery phase of his acute lung injury. A non-surgical conservative approach was taken as the definitive surgical procedure; a complete small-bowel resection was deemed to be associated with an unacceptably high long-term morbidity. However, repeat computed tomography four days later showed complete resolution of the original computed tomography findings. Pneumatosis intestinalis from non-ischaemic origins has been described in association with norovirus and cytomegalovirus. To our knowledge, this is the first time that this has been described in COVID-19.