Introduction: Sickle cell disease (SCD) is a subset of hereditary hemoglobinopathies characterized by chronic hemolysis, vaso-occlusion, and multiorgan complications. Among the concerned complications of vaso-occlusive crisis, acute chest syndrome (ACS) appears to be the leading cause of death in this population. Many studies revealed bacterial pneumonia contributes to a substantial cause of mortality in SCD with ACS. However, the underlying microbial etiology cannot be ascertained in the majority of cases. Viral pneumonia (VP) in a healthy adult commonly leads to uneventful recovery, while the complication and outcome of VP in patients with SCD is poorly understood. Herein, we conducted an analytic study to evaluate the association between VP in hospitalized SCD patients and poor health outcomes.

Method: An analysis was conducted to assess the impact of VP among hospitalized patients with SCD using the National Inpatient Sample database from 2016 to 2021. The outcomes of interest included in-hospital mortality, total hospital charges, length of hospital stay, and incidence of ACS during the stay. Multivariable logistic regression was used to assess the association between VP and inpatient outcomes, including mortality and ACS. The resulting binary outcomes (in-hospital mortality and ACS) were used to calculate the odds ratios (OR) with 95% confidence interval (CI). Linear regression was applied to continuous outcomes (hospital charges and length of stay) to produce coefficient estimates with 95% CI. Both unadjusted and adjusted analyses were performed, with adjustments for relevant demographics (age, gender, race, median household income), Charlson Comorbidity Index, and hospital characteristics (region, teaching status, bed size).

Results: Patients with SCD admitted with VP experienced significantly worse outcomes compared to those without VP. There was a markedly higher risk of in-hospital mortality (adjusted OR 6.00; CI 4.76–7.58, P<.01), increased total hospital charges (adjusted coefficient $39,111.22; CI $32,251.09–$45,971.34, P<.01), and longer hospital stays (adjusted coefficient 3.05 days; CI 2.59–3.52, P<.01). Additionally, the incidence of ACS was significantly elevated (adjusted OR 2.70; CI 2.20–3.32, P<.01). These associations remained significant after controlling for confounders, indicating that VP independently contributes to poorer hospital outcomes and increased healthcare resource utilization in SCD patients.

Discussion: VP presents a serious threat to patients with SCD. The findings of this study reveal a dramatic increase in mortality and healthcare expenses when VP complicates SCD hospitalizations. And the association between symptomatic VP and SCD is strong, and this is likely secondary to impaired immunity with functional asplenia, chronic inflammation, vasculopathy, and chronic pulmonary hypertension. Moreover, VP can in itself cause ACS or further be complicated by bacterial pneumonia. The resultant ACS initiates a vicious cycle of hypoxia and sickling with vaso-occlusion, ultimately leading to increased morbidity and mortality. Based on these results, it is critical to implement vigilant monitoring, early recognition, and aggressive management of viral respiratory infections in SCD patients. Enhanced preventive measures, including vaccination, and improvements in supportive care may mitigate the adverse outcomes identified in this study.

Conclusion: Hospitalized patients with SCD who develop VP have a significantly higher risk of death, incur greater healthcare costs, experience longer hospital stays, and have an increased frequency of ACS compared to those without VP. Proactive prevention, timely intervention, and specialized management approaches are crucial to improving outcomes and reducing mortality and the healthcare burden posed by viral respiratory infections in the SCD population.

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2025
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