Background: Indolent B-cell lymphomas, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenström's macroglobulinemia (WM), represent a heterogeneous group of lymphoproliferative disorders typically associated with prolonged survival. However, their natural history and treatment-related immunosuppression that leads to B-cell depletion and blunted antibody response may predispose patients to severe complications from viral infections. While COVID-19 has highlighted the vulnerability of immunocompromised populations, there is limited data on outcomes of patients with indolent lymphomas hospitalized with acute or acute-on-chronic respiratory failure due to upper respiratory viral infections. This study addresses this gap using a large national database.

Methods: We used the National Inpatient Sample (NIS) database (2017-2021) to identify adult patients hospitalized with acute or acute-on-chronic respiratory failure secondary to viral upper respiratory infections (including COVID-19, Influenza, and RSV). Discharge weights (DISCWT) were applied to generate national estimates. Patients were stratified by the presence of indolent lymphomas (FL, MZL, SLL, WM). Categorical variables were compared using Pearson's chi-square test and continuous variables with Student's t-tests/ANOVA. The primary outcome was in-hospital mortality. Secondary outcomes included the need for mechanical ventilation, ECMO, length of stay (LOS), and total hospitalization charges. Multivariate logistic and linear regression analyses were performed to adjust for potential confounders (age, gender, and Charlson Comorbidity Index, which includes a range of comorbidities such as myocardial infarction, diabetes mellitus, chronic kidney disease, cerebrovascular accidents, and other significant chronic diseases).

Results: Out of 634,892 hospitalizations for acute or acute-on-chronic respiratory failure secondary to viral infections, 436,222 were secondary to COVID-19. 970 out of the 634,892 patients involved had an indolent lymphoma. The mean age for patients without an indolent lymphoma was 63.9 and 63.5 for patients with an indolent lymphoma. The mean Charlson comorbidity index for patients without lymphoma was lower at 2.1 compared to 3.9 in patients with an indolent lymphoma. After adjusting for confounders, patients with indolent lymphomas had significantly higher in-hospital mortality compared to others (20.2% vs 13.2%, adjusted odds ratio [aOR]: 1.35; 95% confidence interval [CI]: 1.15–1.59; p < 0.001).

The use of mechanical ventilation was more frequent in the indolent lymphoma group (21.0% vs 15.1%), though this difference was not statistically significant (aOR: 1.13; 95% CI: 0.97–1.32; p = 0.127). ECMO use was similar between groups (0.82% vs 0.74%; aOR: 0.86; 95% CI: 0.43–1.73; p = 0.697).

Length of hospital stay was substantially longer in the indolent lymphoma cohort (13.7 vs 8.5 days; aOR: 1.51; 95% CI: 1.44–1.57; p < 0.001), and total hospitalization charges were significantly higher ($52,728 vs $23,151; aOR: 2.12; 95% CI: 2.00–2.33; p < 0.001).

Conclusions: Adult patients with indolent lymphomas admitted for acute or acute-on-chronic respiratory failure due to upper respiratory viral infections, especially when it is secondary to COVID-19, since 69% of the viral infections that resulted in an admission were due to it. face significantly worse outcomes, including higher mortality, longer hospital stays, and increased healthcare costs. These findings emphasize the need for heightened preventive strategies, including vaccination and early intervention, in this high-risk population. In the context of the COVID era, this study also highlights the need for increased clinical vigilance when using B-cell-depleting agents such as rituximab, given their potential to worsen infectious outcomes.

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2025
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