Dexamethasone Raises VTE Risk in COVID-19 Cases with Sickle Cell

Treatment with dexamethasone raised the likelihood of venous thromboembolism (VTE) in patients with sickle cell disease (SCD) hospitalized for COVID-19 infection, according to a single-center, retrospective analysis.1

These findings remained consistent with the available literature on the moderate harm of dexamethasone for individuals with SCD and hypoxia owing to SARS-CoV-2 injection.2 However, given the study’s observational nature, Johns Hopkins University investigators noted there may be uncontrolled confounding by indication.1

“Overall, the absence of a clear benefit and suggestion of harm of dexamethasone for patients with SCD indicate further investigation is needed,” wrote the investigative team, led by William M. Garneau, MD, MPH, division of hospital medicine, department of medicine, Johns Hopkins Hospital.1 “These findings should be considered within the limited body of literature examining dexamethasone use for COVID-19 and SCD.”

COVID-19 may have impacted vulnerable individuals with SCD, with a higher risk of hospitalization due to infection, but other risks, including severe illness, mechanical ventilation, or death among those hospitalized have remained unclear among certain SCD genotypes.3 Dexamethasone for COVID-19-related hypoxia became the standard of care following June 2020, but there are lingering concerns about inducing vaso-occlusive crises (VOCs) in those with SCD.

For this analysis, Garneau and colleagues pulled data from the Johns Hopkins CROWN registry for patients who underwent SARS-CoV-2 testing between June 2020 and June 2022.1 Eligible patients for analysis were aged ≥18 years, hospitalized with SARS-CoV-2, and qualified for dexamethasone, based on oxygen saturation ≤94%.

The primary outcome of interest was intensive care unit (ICU) admission, with secondary outcomes including the hospital length of stay, incidence of VTE, follow-up VOC occurring within 30 days of index admission, and in-hospital mortality. A total of 121 participants with SCD and a positive SARS-CoV-2 test were identified in the query and screened for inclusion.

Among this population, 70 patients with SCD were hospitalized for SARS-CoV-2 infection and 30 were eligible for dexamethasone, of whom 13 received dexamethasone. The median age was 33.7 years old and most patients were female (67%), Black (100%), and non-Hispanic or Latino (100%).

Upon analysis, the risk of admission to the OCU was higher in dexamethasone-treated patients, compared with non-treated patients (risk difference, 25%; 95% CI, –3 to 47). Overall, the risk difference was 17% (95% CI, –36 to 53), after adjustments were performed for age, obesity, and total number of Infectious Disease Society of America (IDSA) risk factors.

Further analysis revealed dexamethasone treatment was linked to an increased risk of incident VTE (risk difference, 36%; 95% CI, 8–66), after adjusting for high-risk genotypes, more than 3 hospitalizations, and anticoagulation. The risk of death was similar between dexamethasone treatment and no dexamethasone treatment.

Garneau and colleagues identified a rise in the risk between ICU admission and an increased length of stay in both crude and adjusted analyses, but these associations were not statistically significant. Overall, investigators urged caution on these results, calling for further studies to investigate the risks of dexamethasone in patients with SCD hospitalized with COVID-19.

“Larger studies would strengthen the research on the risk of dexamethasone in this population,” they wrote. “Additionally, these findings were among a primarily unvaccinated cohort of patients and the effects of dexamethasone in patients with prior history of COVID infection or vaccination may be different and merit exploration.”

References

1. Garneau WM, Lankiewicz MJ, Lesko CR, Lauriello AP, Gebo KA, Lanzkron SM. Clinical effects of dexamethasone among patients with sickle cell disease hospitalized with COVID-19: Outcomes from a single academic health system. PLoS One. 2024;19(11):e0313289. Published 2024 Nov 26. doi:10.1371/journal.pone.0313289
2. Hoogenboom WS, Alamuri TT, McMahon DM, et al. Clinical outcomes of COVID-19 in patients with sickle cell disease and sickle cell trait: A critical appraisal of the literature. Blood Rev. 2022;53:100911. doi:10.1016/j.blre.2021.100911
3. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436