Clinical Outcomes in Patients With COVID-19 and Hematologic Disease

Abstract

Background: Patients with hematologic diseases are at higher risk of the SARS-CoV-2 infection and more severe clinical outcomes of the coronavirus disease. CHRONOS19 is an observational prospective cohort study with the aim to determine the short and longer-term clinical outcomes, risk factors for disease severity and mortality, and rates of postinfectious immunity in patients with malignant and nonmalignant hematologic diseases and COVID-19.

Patients and methods: Overall, 666 patients were enrolled in the study, of which 626 were included in the final data analysis. The primary endpoint was 30-days all-cause mortality. Secondary endpoints included COVID-19 complications, rates of ICU admission and mechanical ventilation, outcomes of a hematologic disease in SARS-CoV-2 infected patients, overall survival, and risk factors for disease severity and mortality. Data from 15 centers were collected at 30, 90, and 180 days after COVID-19 was diagnosed and were managed using a web-based e-data capture platform. All evaluations were performed in the pre-omicron period of COVID-19 pandemic.

Results: Thirty-days all-cause mortality was 18.9%. The predominant cause of death (in 80% of cases) were COVID-19 complications. At 180 days, the majority (70%) of additional deaths were due to hematologic disease progression. At a median follow-up of 5.7 [0.03-19.04] months, 6-months overall survival was 72% [95% CI: 0.69-0.76]. One-third of patients had severe SARS-CoV-2 disease. The rate of ICU admission was 22% with 77% of these patients requiring mechanical ventilation, with poor survival rate. A univariate analysis revealed that older age (≥ 60 years), male sex, malignant hematologic disease, myelotoxic agranulocytosis, transfusion dependence, refractory disease or relapse, diabetes among comorbidities, any complications, especially ARDS alone or in combination with CRS, admission to an ICU, and mechanical ventilation were associated with higher risks of mortality. Treatment of the hematologic disease was changed, postponed, or canceled in 63% of patients. At a longer follow-up (90 and 180 days), the status of the hematologic disease changed in 7.5% of patients.

Conclusion: Patients with hematologic disease and COVID-19 have high mortality rates, predominantly due to COVID-19 complications. At a longer-term follow-up, no significant impact of COVID-19 on the course of a hematologic disease was revealed.

Keywords: Leukemia; Lymphomas; Mortality; Risk factors; SARS-CoV-2.

Figure 1

CHRONOS19 study design and patient disposition

Figure 2

Overall survival in patients with various types of hematologic malignancies and COVID-19 who were eligible for the primary endpoint assessment in CHRONOS19. Survival analysis was performed with Kaplan-Maier estimates. Abbreviations: AL, acute leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; CMPN, chronic myeloproliferative neoplasms; HL, Hodgkin's lymphoma; MDS, myelodysplastic syndrome; MM, multiple myeloma; NHL, non-Hodgkin lymphoma

Figure 3

Overall survival in the evaluable population of patients who were eligible for the primary endpoint assessment in CHRONOS19, n = 626: survival estimates (95% CI) at 1, 3, and 6 months after the COVID-19 diagnosis. Survival analysis was performed with Kaplan-Maier estimates.

Figure 4

Forrest plot representing risk factors for COVID-19 mortality (univariate analysis). Abbreviations: ARDS, acute respiratory distress syndrome; CRS, cytokine release syndrome; ECOG, Eastern Cooperative Oncology Group; ICU, intensive care unit; MTA, myelotoxic agranulocytosis.

Figure 5

Impact of a hematologic disease treatment and its schedule change on overall survival. Survival analysis was performed with Kaplan-Maier estimates.