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1.
Blood ; 138(19):315-315, 2021.
Article in English | EuropePMC | ID: covidwho-1601749

ABSTRACT

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 antithrombotic prophylaxis in addition to heparin. Figure 1 Disclosures Barbui:  AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding;Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Iurlo:  Novartis: Speakers Bureau;Incyte: Speakers Bureau;Pfizer: Speakers Bureau;Bristol Myers Squibb: Speakers Bureau. Sobas:  Celgene: Consultancy, Honoraria;Novartis: Consultancy, Honoraria. Fox:  Novartis: Honoraria;Sierra: Honoraria. Palandri:  AOP: Membership on an entity's Board of Directors or advisory committees;CTI: Consultancy;Sierra Oncology: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees. Benevolo:  Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees;Amgen: Speakers Bureau. Harrison:  Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Sierra Oncology: Honoraria;Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Incyte Corporation: Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Constellation Pharmaceuticals: Research Funding;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bonifacio:  Pfizer: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees. Kiladjian:  Taiho Oncology, Inc.: Research Funding;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Incyte Corporation: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;PharmaEssentia: Other: Personal fees;AOP Orphan: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors or advisory committees. Patriarca:  Incyte: Honoraria;Takeda: Honoraria;Argenix: Honoraria;Novartis: Honoraria;Amgen: Honoraria;Pfizer: Honoraria. Griesshammer:  Janssen: Consultancy, Honoraria;Roche: Consultancy, Honoraria;Shire: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Celgene: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Amgen: Consultancy, Honoraria;AOP Orphan: Consultancy, Honoraria;CTI: Consultancy, Honoraria;Gilead: Consultancy, Hono aria;Astra Zeneca: Consultancy, Honoraria. Garcia Gutierrez:  Pfizer: Consultancy, Honoraria, Research Funding;Incyte: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria, Research Funding;Novartis: Consultancy, Honoraria, Research Funding. Osorio:  Janssen, Abbvie, Roche: Consultancy. Koschmieder:  CTI: Membership on an entity's Board of Directors or advisory committees, Other;BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support);Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding;Baxalta: Membership on an entity's Board of Directors or advisory committees, Other;Abbvie: Other: Travel support;Alexion: Other: Travel support;Karthos: Other: Travel support;Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support;Image Biosciences: Other: Travel support;AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding;Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support);Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support);Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding;Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees,Other: Travel support, Research Funding;Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support);Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support);Shire: Honoraria, Other. Vannucchi:  Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors or advisory committees.

2.
Haematologica ; 106(12): 3034-3045, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1547214

ABSTRACT

The COVID-19 pandemic has had a heavy impact on global health and economy and vaccination remains the primary way of controlling the infection. During the ongoing vaccination campaign some unexpected thrombotic events have emerged in subjects who had recently received the AstraZeneca (Vaxzevria) vaccine or the Johnson and Johnson (Janssen) vaccine, two adenovirus vector-based vaccines. Epidemiological studies confirm that the observed/expected ratio of these unusual thromboses is abnormally increased, especially in women in fertile age. The characteristics of this complication, with venous thromboses at unusual sites, most frequently in the cerebral vein sinuses but also in splanchnic vessels, often with multiple associated thromboses, thrombocytopenia, and sometimes disseminated intravascular coagulation, are unique and the time course and tumultuous evolution are suggestive of an acute immunological reaction. Indeed, plateletactivating anti-PF4 antibodies have been detected in a large proportion of the affected patients. Several data suggest that adenoviruses may interact with platelets, the endothelium and the blood coagulation system. Here we review interactions between adenoviral vectors and the hemostatic system that are of possible relevance in vaccine-associated thrombotic thrombocytopenia syndrome. We systematically analyze the clinical data on the reported thrombotic complications of adenovirus-based therapeutics and discuss all the current hypotheses on the mechanisms triggering this novel syndrome. Although, considering current evidence, the benefit of vaccination clearly outweighs the potential risks, it is of paramount importance to fully unravel the mechanisms leading to vaccineassociated thrombotic thrombocytopenia syndrome and to identify prognostic factors through further research.

3.
Sci Rep ; 11(1): 21136, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1493228

ABSTRACT

The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score group), the case-fatality rate was 1.6%, 17.8% in the second and third quartile (high-risk score group) and 53.5% in the fourth quartile (very high-risk score group). The three risk score groups showed good discrimination for the P/F value at admission, and a positive correlation was found for the low-risk class to P/F at 48 h after admission (adjusted R-squared = 0.48). We developed a predictive model of death for people with SARS-CoV-2 infection by including only easy-to-obtain variables (abnormal blood count, BUN, C-reactive protein, sodium and lower SpO2). It demonstrated good accuracy and high power of discrimination. The simplicity of the model makes the risk prediction applicable for patients in the Emergency Department, or during hospitalization. Although it is reasonable to assume that the model is also applicable in not-hospitalized persons, only appropriate studies can assess the accuracy of the model also for persons at home.


Subject(s)
COVID-19/mortality , Machine Learning , Pandemics , SARS-CoV-2 , Aged , Aged, 80 and over , Blood Cell Count , Blood Chemical Analysis , COVID-19/blood , Cohort Studies , Female , Hospital Mortality , Humans , Male , Middle Aged , Models, Statistical , Multivariate Analysis , Oxygen/blood , Pandemics/statistics & numerical data , ROC Curve , Risk Factors , Rome/epidemiology
5.
Curr Hematol Malig Rep ; 16(5): 455-463, 2021 10.
Article in English | MEDLINE | ID: covidwho-1442179

ABSTRACT

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is associated with a high rate of respiratory failure, thromboembolism, bleeding, and death. Patients with myeloproliferative neoplasms (MPNs) are prone to both thrombosis and bleeding, calling for special care during COVID-19. We reviewed the clinical features of MPN patients with COVID-19, suggesting guidance for treatment. RECENT FINDINGS: One study by the European LeukemiaNet collected 175 MPN patients with COVID-19 during the first wave of the pandemic, from February to May 2020. Patients with primary myelofibrosis (PMF) were at higher risk of mortality (48%) in comparison with essential thrombocythemia (ET) (25%) and polycythemia vera (19%); the risk of death was higher in those patients who abruptly discontinued ruxolitinib. In patients followed at home, in regular wards, or in ICU, the thrombosis rate was 1.0%, 2.8%, and 18.4%, respectively. Independent risk factors for thrombosis were ET phenotype, transfer to ICU, and neutrophil/lymphocyte ratio; major bleeding occurred in 4.3% of patients, particularly those with PMF. MPN patients with non-severe COVID-19 treated at home should continue their primary or secondary antithrombotic prophylaxis with aspirin or oral anticoagulants. In the case of hospitalization, patients assuming aspirin should add low molecular weight heparin (LMWH) at standard doses. In contrast, LMWH at intermediate/therapeutic doses should replace oral anticoagulants prescribed for atrial fibrillation or previous venous thromboembolism. Intermediate/high doses of LMWH can also be considered in ICU patients with ET, particularly in the case of a rapid decline in the number of platelets and progressive respiratory failure.


Subject(s)
COVID-19 , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Hemorrhage/epidemiology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/complications , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/diagnosis , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/epidemiology , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/therapy , Myeloproliferative Disorders/complications , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/epidemiology , Myeloproliferative Disorders/therapy , Pandemics , SARS-CoV-2/physiology , Thrombosis/epidemiology
6.
Cancers (Basel) ; 13(19)2021 Sep 23.
Article in English | MEDLINE | ID: covidwho-1438523

ABSTRACT

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) started in December 2019 in China and then become pandemic in February 2020. Several publications investigated the possible increased rate of COVID-19 infection in hematological malignancies. Based on the published data, strategies for the management of chronic Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are provided. The risk of severe COVID-19 seems high in MPN, particularly in patients with essential thrombocythemia, but not negligible in myelofibrosis. MPN patients are at high risk of both thrombotic and hemorrhagic complications and this must be accounted in the case of COVID-19 deciding on a case-by-case basis. There are currently no data to suggest that hydroxyurea or interferon may influence the risk or severity of COVID-19 infection. Conversely, while the immunosuppressive activity of ruxolitinib might pose increased risk of infection, its abrupt discontinuation during COVID-19 syndrome is associated with worse outcome. All MPN patients should receive vaccine against COVID-19; reassuring data are available on efficacy of mRNA vaccines in MPNs.

8.
Am J Hematol ; 96(12): 1580-1586, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1375592

ABSTRACT

The recent association of cerebral venous thrombosis (CVT) with COVID-19 vaccinations prompted the current retrospective review of 74 cases of CVT (median age = 44 years, range 15-85; 61% females) associated with myeloproliferative neoplasms (MPNs), seen at the Mayo Clinic, Catholic University of Rome, and University of Florence, between 1991 and 2021. Disease-specific frequencies were 1.3% (39/2893), 1.2% (21/1811) and 0.2% (3/1888) for essential thrombocythemia, polycythemia vera and primary myelofibrosis, respectively. Cerebral venous thrombosis occurred either prior to (n = 20, 27%), at (n = 32, 44%) or after (n = 22) MPN diagnosis. A total of 72% of patients presented with headaches. Transverse (51%), sagittal (43%) and sigmoid sinuses (35%) were involved with central nervous system hemorrhage noted in 10 (14%) patients. In all, 91% of tested patients harbored JAK2V617F. An underlying thrombophilic condition was identified in 19 (31%) cases and history of thrombosis in 10 (14%). Treatment for CVT included systemic anticoagulation alone (n = 27) or in conjunction with aspirin (n = 24), cytoreductive therapy (n = 14), or both (n = 9). At a median follow-up of 5.1 years (range 0.1-28.6), recurrent CVT was documented in three (4%) patients while recurrent arterial and venous thromboses and major hemorrhage were recorded in 11%, 9% and 14%, respectively. Follow-up neurological assessment revealed headaches (n = 9), vision loss (n = 1) and cognitive impairment (n = 1). The current study lends clarity to MPN-associated CVT and highlights its close association with JAK2V617F, younger age and female gender. Clinical features that distinguish COVID vaccine-related CVT from MPN-associated CVT include, in the latter, lower likelihood of concurrent venous thromboses and intracerebral hemorrhage; as a result, MPN-associated CVT was not fatal.

9.
Haematologica ; 106(12): 3034-3045, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1365528

ABSTRACT

The COVID-19 pandemic has had a heavy impact on global health and economy and vaccination remains the primary way of controlling the infection. During the ongoing vaccination campaign some unexpected thrombotic events have emerged in subjects who had recently received the AstraZeneca (Vaxzevria) vaccine or the Johnson and Johnson (Janssen) vaccine, two adenovirus vector-based vaccines. Epidemiological studies confirm that the observed/expected ratio of these unusual thromboses is abnormally increased, especially in women in fertile age. The characteristics of this complication, with venous thromboses at unusual sites, most frequently in the cerebral vein sinuses but also in splanchnic vessels, often with multiple associated thromboses, thrombocytopenia, and sometimes disseminated intravascular coagulation, are unique and the time course and tumultuous evolution are suggestive of an acute immunological reaction. Indeed, plateletactivating anti-PF4 antibodies have been detected in a large proportion of the affected patients. Several data suggest that adenoviruses may interact with platelets, the endothelium and the blood coagulation system. Here we review interactions between adenoviral vectors and the hemostatic system that are of possible relevance in vaccine-associated thrombotic thrombocytopenia syndrome. We systematically analyze the clinical data on the reported thrombotic complications of adenovirus-based therapeutics and discuss all the current hypotheses on the mechanisms triggering this novel syndrome. Although, considering current evidence, the benefit of vaccination clearly outweighs the potential risks, it is of paramount importance to fully unravel the mechanisms leading to vaccineassociated thrombotic thrombocytopenia syndrome and to identify prognostic factors through further research.

11.
Blood Cancer J ; 11(6): 115, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1275905
12.
Int Labour Rev ; 2021 Jun 19.
Article in English | MEDLINE | ID: covidwho-1273098

ABSTRACT

COVID-19-induced digital surveillance has ballooned in an unprecedented fashion, causing a reconfiguration of power relationships in professional settings. This article critically concentrates on the interplay between technology-enabled intrusive monitoring and the managerial prerogatives augmentation in physical and digital workplaces. It portrays excessive control as the common denominator for "essential" and "remotable" activities, besides discussing the various drawbacks of the two categories of workers during the pandemic. It also assesses the adequacy of the current EU legal framework in addressing the expansion of data-driven management. Social dialogue, empowerment and digital literacy are identified as effective solutions to promote organisational flexibility, well-being and competitiveness.

13.
Mediterr J Hematol Infect Dis ; 13(1): e2021032, 2021.
Article in English | MEDLINE | ID: covidwho-1234866

ABSTRACT

The current COVID-19 pandemic requires revisiting our current approach to major blood disorders, including ITP (Immune Thrombocytopenia), stirring up the production of several disease-specific practical guidelines. This report describes an updated version of consensus-based practical guidelines on the management of ITP, adapted to the Italian health system and social context. It highlights the role of the hematologist in offering guidance for choosing differentiated approaches in relation to specific circumstances and is intended to provide them with a useful tool for sharing the decision-making process with their patients. Probably, the greatest risk to avoid for a patient with suspected, ongoing or relapsed ITP - that is not severe enough to place him or her at risk for major bleeding - is to be infected in non-hospital and hospital healthcare settings. This risk must be carefully considered when adapting the diagnostic and therapeutic approach. More in detail, the document first addresses the appropriate management for COVID-19 negative patients with newly diagnosed ITP or who experience a relapse of previous ITP, according to first and second lines of treatment and then the management of COVID-19 positive patients according to their severity, from paucisymptomatic to those requiring admission to Intensive Cure Units (ICU). The pros and cons of the different treatments required to correct platelet count are discussed, as are some specific situations, including chronic ITP, splenectomy, thromboembolic complication and anti COVID-19 vaccination.

16.
Blood Cancer J ; 11(2): 21, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1075184

ABSTRACT

In a multicenter European retrospective study including 162 patients with COVID-19 occurring in essential thrombocythemia (ET, n = 48), polycythemia vera (PV, n = 42), myelofibrosis (MF, n = 56), and prefibrotic myelofibrosis (pre-PMF, n = 16), 15 major thromboses (3 arterial and 12 venous) were registered in 14 patients, of whom all, but one, were receiving LMW-heparin prophylaxis. After adjustment for the competing risk of death, the cumulative incidence of arterial and venous thromboembolic events (VTE) reached 8.5% after 60 days follow-up. Of note, 8 of 12 VTE were seen in ET. Interestingly, at COVID-19 diagnosis, MPN patients had significantly lower platelet count (p < 0.0001) than in the pre-COVID last follow-up.This decline was remarkably higher in ET (-23.3%, p < 0.0001) than in PV (-16.4%, p = 0.1730) and was associated with higher mortality rate (p = 0.0010) for pneumonia. The effects of possible predictors of thrombosis, selected from those clinically relevant and statistically significant in univariate analysis, were examined in a multivariate model. Independent risk factors were transfer to ICU (SHR = 3.73, p = 0.029), neutrophil/lymphocyte ratio (SHR = 1.1, p = 0.001) and ET phenotype (SHR = 4.37, p = 0.006). The enhanced susceptibility to ET-associated VTE and the associated higher mortality for pneumonia may recognize a common biological plausibility and deserve to be delved to tailor new antithrombotic regimens including antiplatelet drugs.


Subject(s)
Bone Marrow Neoplasms/epidemiology , COVID-19/epidemiology , Myeloproliferative Disorders/epidemiology , Thrombocythemia, Essential/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Aged , Aged, 80 and over , Bone Marrow Neoplasms/complications , COVID-19/complications , Cohort Studies , Europe/epidemiology , Female , Humans , Male , Middle Aged , Myeloproliferative Disorders/complications , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2/physiology , Thrombocythemia, Essential/complications
17.
Leukemia ; 35(2): 485-493, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065836

ABSTRACT

We report the clinical presentation and risk factors for survival in 175 patients with myeloproliferative neoplasms (MPN) and COVID-19, diagnosed between February and June 2020. After a median follow-up of 50 days, mortality was higher than in the general population and reached 48% in myelofibrosis (MF). Univariate analysis, showed a significant relationship between death and age, male gender, decreased lymphocyte counts, need for respiratory support, comorbidities and diagnosis of MF, while no association with essential thrombocythemia (ET), polycythemia vera (PV), and prefibrotic-PMF (pre-PMF) was found. Regarding MPN-directed therapy ongoing at the time of COVID-19 diagnosis, Ruxolitinib (Ruxo) was significantly more frequent in patients who died in comparison with survivors (p = 0.006). Conversely, multivariable analysis found no effect of Ruxo alone on mortality, but highlighted an increased risk of death in the 11 out of 45 patients who discontinued treatment. These findings were also confirmed in a propensity score matching analysis. In conclusion, we found a high risk of mortality during COVID-19 infection among MPN patients, especially in MF patients and/or discontinuing Ruxo at COVID-19 diagnosis. These findings call for deeper investigation on the role of Ruxo treatment and its interruption, in affecting mortality in MPN patients with COVID-19.


Subject(s)
COVID-19/mortality , Myeloproliferative Disorders/mortality , Pyrazoles/administration & dosage , SARS-CoV-2/isolation & purification , Withholding Treatment/statistics & numerical data , Aged , COVID-19/complications , COVID-19/transmission , COVID-19/virology , Europe/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/epidemiology , Myeloproliferative Disorders/virology , Nitriles , Prognosis , Pyrimidines , Retrospective Studies , Survival Rate
19.
Br J Haematol ; 191(2): 207-211, 2020 10.
Article in English | MEDLINE | ID: covidwho-652703

ABSTRACT

A low count of CD4+ and CD8+ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID-19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD-1 expression on both CD4+ T and CD8+ T cells in 42 COVID-19 patients when compared to controls. Higher CD95 expression in CD4+ cells correlated with lower CD4+ counts. A higher expression of CD95 in CD4+ and CD8+ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen-activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID-19 infection.


Subject(s)
CD4-Positive T-Lymphocytes/chemistry , CD8-Positive T-Lymphocytes/chemistry , COVID-19/immunology , Lymphocyte Subsets/chemistry , Lymphopenia/etiology , Programmed Cell Death 1 Receptor/blood , fas Receptor/blood , Adult , Aged , Aged, 80 and over , Aging/blood , Aging/immunology , Apoptosis , COVID-19/blood , COVID-19/complications , Female , Humans , Lymphocyte Count , Male , Middle Aged , Prognosis , SARS-CoV-2
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