Second versus first wave of covid-19 in patients with mpn

Introduction. MPN-COVID is a European LeukemiaNet cohort study, launched in March 2020 in patients with myeloproliferative neoplasms (MPN) with COVID-19. The first cohort of 175 cases was analyzed at the end of first wave (July 2020) and results provided estimates and risk factors of overall mortality (Barbui T. Leukemia, 2021), thrombosis incidence (Barbui T. Blood Cancer J, 2021), and post-COVID outcomes (Barbui T. Blood Cancer J, 2021). In the second wave of pandemic (June 2020 to June 2021), case-fatality risk in the general population has been found variable across different countries, and no information is available in MPN patients with COVID-19 diagnosed during the second wave in comparison with those of the first wave. Methods. In an electronic case report form, we registered a total of 479 cases of ET (n=161, 34%), PV (n=135, 28%), pre-PMF (n=49, 10%) and overt MF (n=134, 28%), from 39 European hematology units (Italy, Spain, Germany, France, UK, Poland, Croatia). Of these, 304 were diagnosed COVID-19 during the second wave. Results. Patients in the second wave were significantly different from those in the first wave, including parameters such as age (median: 63 vs. 71 years, p<.001), sex (females: 52% vs. 42%, p=0.037), MPN category (MF 24% vs. 34%, p=0.020), comorbidity (at least one comorbidity 63% vs. 74%, p=0.012), disposition (home: 68% vs. 23%, regular ward: 29% vs. 66%, ICU: 3% vs. 11%, p<.001), need of respiratory support (28% vs. 59%, p<.001) and degree of systemic inflammation (C-Reactive Protein: 51% vs. 74%, p=0.008;Neutrophil to Lymphocyte Ratio: 4.1 vs. 5.4, p=0.038). In regard to COVID-19-directed therapy, in the second wave steroids were more frequently prescribed (28% vs. 40%, p=0.007), while the use of antibiotics, antivirals, hydroxychloroquine and experimental therapies was significantly less frequent (p<.001 for all the differences). Interestingly, only 4 out of 46 patients (8.7%) discontinued Ruxolitinib during second-wave acute COVID (all MF admitted to regular ward). In the two waves, distribution probability of COVID-19 incidence by Kernel method showed a substantially similar shape, whereas the two incidence peaks were associated with very different mortality, as reported in Fig. 1A. The difference between the probability of death was highly significant during the first (n=175) vs. second (n=304): 31% vs. 9% at 60 days from COVID-19 diagnosis, respectively (p<.001) (Fig. 1B). Of note, among 26 deaths, 4 (15%) occurred at home, 19 (73%) on regular wards and 3 (12%) in the ICU, and death more frequently afflicted patients with (n=17, 65%) than ET (n=5, 19%) and PV (n=4. 15%) (p<.001). Independent risk factors for death in a multivariate Cox regression model fitted on the whole cohort and adjusted for the wave to which patients belonged, were age over 70 years (HR=5.2, 95% CI 1.8-15.1, p=0.002), male sex (HR=1.9, 95% CI 1.1-3.1, p=0.016), COVID-19 severity revealed by the need for respiratory support (HR=4.5, 95% CI 1.9-10.7, p=0.001), and Ruxolitinib discontinuation (HR=3.0, 95% CI 1.3-6.9, p=0.011). Conversely, in patients who continued this drug, no risk was documented (HR=1.21, p=0.566). Taking into account death as competing event, the second outcome of interest was the incidence of thrombosis, wich occurred in a significantly lower proportion of patients in the second wave compared to the first one (n=5 [1.6%] vs. n=14 [8.0%] at +60 days, respectively, SHR=0.20, p=0.002) (Fig. 1C). All the events, but one (n=4/5) were venous and were reported in patients with ET (SHR=4.4, 95% CI 1.8-10.7, p=0.001). Conclusions. This is the largest series of MPN patients who incurred COVID-19 from June 2020 onward, namely during the 'second COVID-19 wave'. Compared to the first wave, the second one recorded a lower overall COVID-19 severity, but Ruxolitinib discontinuation still remained a risk factor for a dismal outcome. Greater vulnerability of ET than PV in developing venous thrombosis was confirmed also during the second wave. This finding suggests that ET warrants a specific antithrombo ic prophylaxis in addition to heparin.

Smart specialisation strategies and energy transition: An exploratory analysis of the case of the Basque Country*

Energy transition is a core element of the sustainability transition around which the European Union's post-COVID recovery strategies are built. While these strategies are being designed primarily by EU Member States, the regional level will be critical for their success. Firstly, because regions are key ‘implementers on-the ground' of European and national policies. Secondly, because the placespecificities of regions make them ideal ‘laboratories' for experimenting with the innovations needed for sustainability transitions. This opens an important research question around how regional innovation policy, and more precisely how the regional smart specialisation strategies (S3) that have been developed over recent years, could provide a ‘ready-made' framework for discovery and experimentation oriented explicitly to energy transitions. This paper explores this question by combining discussion of the concepts of S3 and energy transitions with an exploratory analysis of the S3 experience in the specific case of the Basque region. The paper highlights that moving from a S3 to a Sustainable S3 (or S4) will require enhancing the connectedness of different parts of existing strategies so that energy transition goals are approached in a holistic manner. La transición energética es un elemento clave en la transición a la sostenibilidad en torno a la cual se están creando las estrategias de recuperación pos-COVID en la Unión Europea. Aunque dichas estrategias son diseñadas fundamentalmente por los estados miembros de la UE, el ámbito regional puede ser crítico para el éxito de las mismas. En primer lugar, porque las regiones son «actores clave sobre el terreno» de las políticas nacionales y europeas. Segundo, porque las características de cada región las convierten en ‘laboratorios' ideales para experimentar con las innovaciones necesarias para la transición hacia la sostenibilidad. Esto plantea una importante cuestión de investigación sobre cómo las políticas regionales de innovación y, más concretamente, cómo las estrategias regionales de especialización inteligente (S3) que han sido desarrolladas en los últimos años, podrían aportar un marco ‘ready-made' para la experimentación y el descubrimiento orientados explícitamente a transiciones energéticas. Este artículo analiza esta cuestión combinando el debate sobre los conceptos de S3 y transiciones energéticas, con un análisis exploratorio de la experiencia S3 en el caso específico de la región vasca. El artículo pone de manifiesto que pasar de un S3 a un S3 sostenible (o S4) exigirá la mejora de la conexión entre diferentes partes de las estrategias existentes para que las metas de la transición energética se aborden de manera holística. © 2021. All Rights Reserved.