Outcomes of SARS-CoV-2 infection in Ph-neg chronic myeloproliferative neoplasms: results from the EPICOVIDEHA registry

Philadelphia-negative chronic myeloproliferative neoplasms; SARS-CoV-2; Essential thrombocytemiaNeoplàsies mieloproliferatives cròniques filadèlfia negatives; SARS-CoV-2; Trombocitèmia essencialNeoplasias mieloproliferativas crónicas filadelfia negativas; SARS-CoV-2; Trombocitemia esencialBackground: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk. Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19). Design: This is an observational study. Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020. Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19–197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58–77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357–3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363–3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363–3.521). Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA)

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible

COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and &gt;80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves.tThe 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts

Application of mini-MLST and whole genome sequencing in low diversity hospital extended-spectrum beta-lactamase producing Klebsiella pneumoniae population

Studying bacterial population diversity is important to understand healthcare associated infections’ epidemiology and has a significant impact on dealing with multidrug resistant bacterial outbreaks. We characterised the extended-spectrum beta-lactamase producing K. pneumoniae (ESBLp KPN) population in our hospital using mini-MLST. Then we used whole genome sequencing (WGS) to compare selected isolates belonging to the most prevalent melting types (MelTs) and the colonization/infection pair isolates collected from one patient to study the ESBLp KPN population’s genetic diversity. A total of 922 ESBLp KPN isolates collected between 7/2016 and 5/2018 were divided into 38 MelTs using mini-MLST with only 6 MelTs forming 82.8% of all isolates. For WGS, 14 isolates from the most prominent MelTs collected in the monitored period and 10 isolates belonging to the same MelTs collected in our hospital in 2014 were randomly selected. Resistome, virulome and ST were MelT specific and stable over time. A maximum of 23 SNV per core genome and 58 SNV per core and accessory genome were found. To determine the SNV relatedness cut-off values, 22 isolates representing colonization/infection pair samples obtained from 11 different patients were analysed by WGS with a maximum of 22 SNV in the core genome and 40 SNV in the core and accessory genome within pairs. The mini-MLST showed its potential for real-time epidemiology in clinical practice. However, for outbreak evaluation in a low diversity bacterial population, mini-MLST should be combined with more sensitive methods like WGS. Our findings showed there were only minimal differences within the core and accessory genome in the low diversity hospital population and gene based SNV analysis does not have enough discriminatory power to differentiate isolate relatedness. Thus, intergenic regions and mobile elements should be incorporated into the analysis scheme to increase discriminatory power