Impact of the COVID-19 Pandemic on Mortality in Hospitalizations with Diffuse Large B-Cell Lymphoma: A Population-Based Study

Introduction

Diffuse Large B-cell Lymphoma (DLBCL) is the most common subtype of Non-Hodgkin Lymphoma. Furthermore, COVID-19 has been associated with an increased risk for the development of DLBCL. The link between viral infections and their associated chronic inflammatory state and the development of DLBCL is well-established. The population level impact of the COVID-19 pandemic on short-term mortality time trends of patients with DLBCL was not known.

Methods

We used publicly available, de-identified, and state-wide data to conduct a population-base cohort study of hospitalizations aged ≥ 18 years admitted to acute care hospitals in Texas during 2016-2022. DLBCL was identified using International Classification of Diseases, Tenth Revisions, Clinical modification codes C833x selected from Clinical Classification Software Refined category NEO058: Non-Hodgkin lymphoma. Short-term mortality was defined as in-hospital mortality or discharge to a hospice. The response variables are pre-pandemic time trend, level change, change in time trend, and final time trend from Q1 of 2016 through Q4 of 2022. The primary analysis method was interrupted time series analysis (ITSA) based on multilevel logistic regression with results reported as average marginal effects per quarter (AME) and 95% confidence intervals (95% CI) in changes to the absolute probability of mortality. The matched pairs t-test was applied to ITSA and counterfactual predicted probabilities to further elucidate the impact of the COVID-19 pandemic on our study population. Sensitivity analyses was performed for hospitalizations admitted to the ICU and for hospitalizations without a diagnosis of COVID-19.

Results

A total of 36,789 hospitalizations were included in the study of which 14,814 (40.3%) occurred during the pandemic period. Unadjusted short-term mortality was lower in the pre-COVID period compared to the post-pandemic period (8.2% vs 10.2%). The pre-COVID short-term mortality time trend was negative (AME -0.23% / quarter, 95% CI [-0.31% to -0.15%], p < 0.0001). The change in time trend was positive (AME 0.27%, 95% CI [0.14% to 0.41%], p = 0.0001) and the change in level was also positive (AME 2.01%, 95% CI [0.94% to 3.09%], p = 0.0002). The final time trend was not significant (AME 0.04%, 95% CI [-0.06% to 0.15%], p = 0.4364). The point estimate and 95% CI for the difference between ITSA predicted and counterfactual predicted probabilities of mortality was 3.56% (3.50% to 3.63%).

Conclusions

Pre-pandemic time trends have been significantly disrupted by COVID-19, including in short-term mortality among hospitalizations with a diagnosis of DLBCL. The onset of the pandemic was associated with an immediate 2% increase in the absolute short-term mortality and positive change in the time trend. Short-term mortality rates have remained elevated with no significant time trend. The average impact on short-term mortality is estimated at over 3%. While the immediate increase may be explained by the additive effect of COVID-19 as an independent risk factor for mortality, the fact that it remains elevated as global COVID-19 cases decline suggests a more permanent deterioration in prognosis for affected patients.

No relevant conflicts of interest to declare.