Abstract: Main aim of this systematic review is to quantify the risk and identify  predictors of clinical evolution of SARS-CoV-2 in hematological patients  compared to different control populations. Two independent reviewers  screened the literature assessing clinical outcomes of SARS-CoV-2  infection in adult patients with active hematological malignancies  published up to June 2021. Primary outcome was COVID-19 related  mortality, secondary outcomes were hospital and intensive-care  admission, mechanical ventilation (MV), and thromboembolic events.  Variables related to study setting, baseline patients' demographic,  comorbidities, underlying hematological disease, ongoing chemotherapy,  COVID-19 presentation, and treatments were extracted. A total of 67  studies including 10,061 hematological patients and 111,143 controls  were included. Most of the studies were retrospective cohorts (51  studies, 76%) and only 19 (13%) provided data for a control group. A  significant increased risk of clinical progression in the hematological  population compared to the controls was found in terms of COVID-19  related mortality (OR, 2.12; 95% CI, 1.77-2.54), hospitalization (OR,  1.98; 95% CI, 1.15-3.43), intensive-care admission (OR, 1.77; 95% CI,  1.38-2.26), and MV (OR, 2.17; 95% CI, 1.71-2.75). The risk remained  significantly higher in the subgroup analysis comparing hematological  patients versus solid cancer. Meta-regression analysis of uncontrolled  studies showed that older age, male sex, and hypertension were  significantly related to worse clinical outcomes of COVID-19 in  hematological population. Older age and hypertension were found to be  associated also to thromboembolic events. In conclusion, hematological  patients have a higher risk of COVID-19 clinical progression compared to  both the general population and to patients with solid cancer.

Keywords: COVID-19; determinants; hematological malignancies; mortality; severity.