ABSTRACT
Background: Philadelphia-negatie chronic myeloproliferatie neoplasms (MPN) typically incur high rates of thrombosis and infections and cytoreductie drugs may modulate such risks. Aims: The present analysis aims at assessing the seerity and outcomes of MPN facing coronairus disease 2019 (COVID-19). Hence, we aimed to assess the impact of immunosuppressie agents and comorbidity burden in COVID- 19 outcome. Methods: The EPICOVIDEHA registry is an online surey (www.clinicalsureys.net) that has collected since April 2020 until January 2022 5,445 cases of COVID-19 in indiiduals with baseline haematological malignancies (Salmanton-García et al, 2021 Hemasphere) The surey is promoted by the European Hematology Association - Infectious Diseases Working Party (EHA-IDWP) and has been approed centrally by the Institutional Reiew Board and Ethics Committee of Fondazione Policlinico Uniersitario A. Gemelli - IRCCS - Uniersità Cattolica del Sacro Cuore, Rome, Italy (Study ID: 3226). Results: Oerall, 308 patients (5.6%) with MPN were obsered for a median of 102 days (IQR: 21-223, range 22-97) after COVID-19 diagnosis. Median age at infection was 69 years (IQR: 58-77, range 22-97) and at least one comorbidity was reported from most of the indiiduals (62.6%, n = 193). A large portion of patients had a history of cardiopathy (n=109, 35.4%), diabetes (n=40, 15.9%), or chronic pulmonary disease (n=44, 14.3%). Myelofibrosis (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) decreased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. (MF) (n=140, 45.4%) was the most prealent baseline malignancy, with 18 MF patients (12.9%) reporting 3 or more comorbidities. Out of the whole cohort, 72 patients (42.8% of MF) receied immunosuppressige therapies including steroids, immunomodulatory drugs (IMiDs) or JAK-inhibitors. Hospitalization and consecutie admission to intensie care unit was required for 187 (60.7%) and 45 (24%) patients, respectiely. At multiariate logistic regression, Hospital admission was predicted by age >70 years (OR 2.809;95% CI 1.651-4.779), exposure to immunosuppressie therapies (OR 2.802;95% CI 1.5380-5.103) and comorbidity burden. During the study follow-up (median 101 days;range 21-222) 84 patients deceased after a median time of 14 days (IQR: 8-49, range 0-457) since COVID-19 diagnosis. The fatality rate (FR) dec eased from 40.3% (50 out of 124) in the first two quarters of year 2020 to 15.8% (3 out of 19) in the first two quarters of year 2021 (p<0.05). Death was principally attributable to COVID-19 in 58 patients (69.0%) and contributable by COVID-19 in 15 (17.9%). FR was particularly high (54 out of 140, 38.6%) in MF patients and in patients receiing immunosuppressie agents (32 out of 86, 37%). Moreoer, FR increased from 13.0% in indiiduals with no comorbidity to 36.0% and 62.1% in those with >2 or >3 comorbidities, respectiely. More specifically, three comorbidities independently increased the FR: chronic cardiopathy (HR 1.653;95%CI 1.017-2.687), chronic pulmonary disease (HR 1.847;95% CI 1.097-3.109), and diabetes mellitus (HR 1.712;95% CI 1.006-2.914). A heay comorbidity burden, namely 3 or more comorbidities (HR 2.956;95% CI 1.403-6.227), adanced age, namely >70 years (HR .809;95% CI 1.651-4.779), myelofibrosis (HR 2.501;95% CI 1.384-4.519), and ICU admission (HR 2.669;95% CI 1.641-4.342) independently predicted FR. Summary/Conclusion: COVID-19 infection led to a particularly dismal outcome in patients exposed to immunosuppressie agents and in those with chronic heart or pulmonary diseases, or diabetes. These data allow to tailor future strategies for preenting seere COVID-19 in MPN patients. (Table Presented).