Venous thromboembolism (VTE) is a life-threatening complication observed among patients with sickle cell disease (SCD) and also among those with severe COVID-19 infection. Although prior studies show that patients with SCD are at risk of severe COVID-19 illness, it remains unclear if COVID-19 infection further increases VTE risk for this population. We hypothesized that patients with SCD hospitalized for COVID-19 would have higher VTE rates than those hospitalized for other causes. Using electronic health record data from a multisite research network, TriNetX, we identified 2 groups of patients with SCD hospitalized during 2020: (1) with COVID-19 and (2) without COVID-19. We compared VTE rates using risk ratios estimated based on adjusted Poisson regression model with log link and robust error variances. Of the 281 SCD patients hospitalized with COVID-19 and 4873 SCD patients hospitalized without COVID-19 , 35 (12.46%) and 418 (8.58%) had incident VTE within 6 months of the index hospitalization respectively. After adjusting for differences in baseline characteristics, no significant differences in VTE rates within 6 months were found between the 2 groups (adjusted relative risk, 1.06 [95% confidence interval, 0.79-1.41]). These data suggest that hospitalization with COVID-19 does not further increase VTE risk in patients with SCD.

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413.