Decoding the Historical TALE: COVID-19 Impact on Hematological Malignancy Patients - Insights from 2020 to 2022
Authors: Marchesi Francesco , Salmanton-García Jon , Farina Francesca , Weinbergerova Barbora , Itri Federico , Dávila-Valls Julio , Martín-Pérez Sonia , Glenthoej Andreas , Hersby Ditte , Da Silva Maria Gomes , Nunes-Rodrigues Raquel , Cordoba Raul , Lopez Garcia Alberto , Emarah Ziad , El-Ashwah Shaimaa , Bilgin Yavuz M. , Rahimli Laman , Cornely Oliver , Pagano Livio 
Published: December 2023

Introduction
From the onset of the COVID-19 pandemic, hematological malignancy patients have been at high risk of both contracting SARS-CoV-2 and experiencing its most severe effects, leading to hospitalization and high fatality rates. While the introduction of anti-SARS-CoV-2 vaccines, specific antivirals, and monoclonal antibodies significantly lessened the impact on otherwise healthy individuals, the same cannot always be said for patients with hematological malignancies due to their compromised immune systems.
Methods
The EPICOVIDEHA registry, part of the EHA-SWG Infections in Hematology, has been actively compiling data on COVID-19 cases in patients with hematological malignancies from the pandemic's onset, spanning diverse geographic locations worldwide. This registry has facilitated the acquisition of comprehensive epidemiological data, enabling a thorough analysis of the evolving patterns in COVID-19 incidence and characteristics during the initial three years of the pandemic.
Results
As of December 2022, the EPICOVIDEHA registry recorded 8,767 cases of COVID-19 in hematological malignancy patients from 152 centers in 41 countries. Of these cases, 42% were female. Non-Hodgkin's lymphoma accounted for 31% of the cases, followed by multiple myeloma at 17%, chronic lymphocytic leukemia at 13%, and acute myeloid leukemia at 12%, showing consistent proportions over time. Chronic cardiopathy emerged as the most prevalent non-malignant underlying condition, increasing from 32% during the first semester of 2020 to 44% in the second semester of 2022. Critical infections decreased significantly from 19% at the beginning of the pandemic to 4% in the second semester of 2022 (p=0.004). Overall mortality dropped from 29% at the pandemic's onset to 4% after three years (p&lt;0.001). Survival rates for hematological malignancy patients consistently improved with each passing semester (p&lt;0.001). Factors associated with mortality included increased age (HR 1.037, p&lt;0.001), two or more comorbidities (HR 1.244, p&lt;0.001), active malignancy at COVID-19 onset (HR 1.832, p&lt;0.001), pulmonary symptoms (HR 1.299, p=0.003), and hospitalization (HR 12.767, p&lt;0.001), particularly in the intensive care unit (HR 33.684, p&lt;0.001). Conversely, factors linked to increased survival were anti-SARS-CoV-2 vaccination (1-2 doses: HR 0.681, p&lt;0.001; 3+ doses: HR 0.451, p&lt;0.001) and experiencing the COVID-19 episode in 2022 (HR 0.427, p&lt;0.001) (Figure 1A). Initially, COVID-19 was the primary cause of mortality in 70% of the cases, decreasing to 42% by the second semester of 2022 (Figure 1B).
Conclusion
Our study revealed that patients with hematological malignancies face an elevated vulnerability to severe outcomes, resulting in higher hospitalization and mortality rates over time. However, there was a decline in critical infections and mortality rates during the study period. While factors associated with mortality remained consistent, vaccination and encountering COVID-19 more recently were linked to improved survival. Our findings emphasize the importance of continuous monitoring and targeted interventions to optimize outcomes for this vulnerable group during the pandemic and beyond.