An analysis of reported cases of hemophagocytic lymphohistiocytosis (HLH) after COVID-19 vaccination

Hum Vaccin Immunother. 2023 Aug;19(2):2263229. doi: 10.1080/21645515.2023.2263229. Epub 2023 Oct 9.

Abstract

Although COVID-19 vaccines are an effective public health tool to combat the global pandemic, serious adverse events, such as hemophagocytic lymphohistiocytosis (HLH), caused by them are a concern. In this systematic review, cases of HLH reported after COVID-19 vaccination have been examined to understand the relationship between the two and propose effective therapeutic strategies. Furthermore, ruxolitinib's potential as a cytokine inhibitor and its affinity for CD25 were initially assessed through molecular docking, aiming to aid targeted HLH therapy. PubMed and Web of Science databases were searched for published individual case reports on the occurrence of HLH after the administration of any COVID-19 vaccine. A total of 17 articles (25 patients) were included in this qualitative analysis. Furthermore, molecular docking was employed to investigate the therapeutic potential of ruxolitinib for HLH after COVID-19 vaccination. The mean age of patients who developed HLH after COVID-19 vaccination was 48.1 years. Most HLH episodes occurred after the BNT162b2 mRNA COVID-19 vaccination (14/25 cases) and to an extent after the ChAdOx1 nCov-19 vaccination (5/25 cases). Almost all affected patients received steroid and antibiotic therapy. Three patients died despite treatment because of esophagus rupture, neutropenic fever, bacteroides bacteremia, refractory shock, and encephalopathy and shock. Visual docking results of IL-2 Rα and ruxolitinib using the Discovery Studio 2019 Client software yielded a model score of 119.879. The findings highlight the importance of considering and identifying the adverse effects of vaccination and the possibility of using ruxolitinib for treating HLH after COVID-19 vaccination.

Keywords: BNT162b2 mRNA vaccine; COVID-19 vaccine; HLH; IL-2R; cytokine storm; hemophagocytic lymphohistiocytosis; ruxolitinib.

Publication types

  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BNT162 Vaccine
  • COVID-19 Vaccines / adverse effects
  • COVID-19* / complications
  • COVID-19* / prevention & control
  • ChAdOx1 nCoV-19
  • Humans
  • Lymphohistiocytosis, Hemophagocytic* / drug therapy
  • Lymphohistiocytosis, Hemophagocytic* / etiology
  • Middle Aged
  • Molecular Docking Simulation

Substances

  • COVID-19 Vaccines
  • ruxolitinib
  • BNT162 Vaccine
  • ChAdOx1 nCoV-19

Grants and funding

This study was funded by the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya hospital of Central South University [YX202212].