Background: Risk factors for severe COVID-19 in myeloproliferative neoplasms (MPN) have been extensively explored. However, no information is available on risk factors to hospitalization at COVID-19 diagnosis. Aims: To provide an evidence-based triage and inform for a timely and antiviral therapy prescription in early phases of viral replication. Methods: The MPN-COVID study is still enrolling consecutive adult MPN patients with COVID-19 infection since February 15, 2020. Among 479 patients (ET n=175, PV n=158, MF n=91, and pre-PMF n=55) with COVID-19 from Feb 2020 to Jun 2021, 248 (52%) were managed at home and 231 (48%) were hospitalized. Results: Univariate analysis Compared to outpatients, those admitted to hospital were more likely to be men (58.9% vs. 45.2%, p=0.003), older than 70 years (61.3% vs. 29.0%, p<.001), with at least one comorbidity (79.7% vs. 55.5%, p<.001) and a history of thrombosis (26.5% vs. 16.6%, p=0.008). Overt myelofibrosis (MF) cases were more frequent in hospital (38.5% vs. 18.1%, p<.001) than PV, ET or pre-PMF. Ruxolitinib was more frequently used in patients who underwent to hospital than managed at home. (25.7% vs. 12.1%, p<.001). In comparison with outpatients, hospitalized cases had a significantly lower median values of hemoglobin (12.1 vs. 13.3 g/dL, p<.001), platelets (250 vs. 390 x109/L, p<.001), absolute lymphocytes (0.8 vs. 1.4 x109/L, p<.001) and higher neutrophil counts (5.1 vs. 4.5 x109/L, p=0.022), leading to a significant increase of neutrophil to lymphocyte ratio (NLR) (6.6 vs. 3.2, p<.001). Compared to lymphocytopenia, the best sensitivity and specificity was found for NLR, whose AUC was 77.28% by ROC analysis. Multivariate analysis By adjusting for sex, comorbidity, fever, systemic symptoms, O2 saturation, previous thrombosis, MPN type, ruxolitinib exposure, and first vs. subsequent waves and vaccination period, three factors emerged as independent predictors of hospitalization: age over 70 years, (OR=3.02, p=0.038), dyspnea (OR=7.23, p<.001) and NLR ≥4, (OR=6.94, p<.001). Interaction model of risk factors In a model fitted to test the interaction terms of the three significant variables, we evaluated the marginal effect of NLR and dyspnea across different age classes (Figure) and found that in younger patients (i.e., from 50 to 70 years) dyspnea was the stronger predictor than increased NLR; conversely, both dyspnea and NLR showed a high and comparable marginal effect in age >80 years. Remarkably, the probability of hospitalization consistently exceeded 90% for any age group when dyspnea and NLR were concomitantly present, and their combination was more prevalent in MF (42%) than in the other phenotypes (24%, 25% and 29% in pre-PMF, PV and ET patients, respectively). In addition to predict hospitalization, dyspnea and NLR≥4 were also associated with severity of COVID-19 illness in terms of respiratory support at hospitalization (OR=2.44, p=0.023). Of note, only age >70 years and NLR higher than 6 were predictors of survival in hospitalized patients (OR=3.24, p=0.007 and OR=5.41, p=0.041, respectively). Image:Summary/Conclusion: For triage purposes of MPN patients tested positive for COVID-19, dyspnea, age and NLR are powerful predictors of hospitalization and identify patients at higher probability of invasive or non-invasive respiratory support and survival, particularly in overt MF. This MPN subgroup at high risk for progression to severe COVID-19 disease should be prioritized for antiviral therapy, even in the ambulatory setting.