Hemophagocytic lymphohistiocytosis after SARS-CoV-2 vaccination

Infection. 2022 Oct;50(5):1399-1404. doi: 10.1007/s15010-022-01786-y. Epub 2022 Feb 26.

Abstract

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to the approval of novel vaccines with different mechanisms of action. Until now, more than 4.7 billion persons have been vaccinated around the world, and adverse effects not observed in pre-authorization trials are being reported at low frequency.

Methods: We report a case of severe hemophagocytic lymphohistiocytosis (HLH) after SARS-CoV-2 immunization and performed a literature search for all reported cases of COVID-19 vaccine-associated HLH.

Results: A 24-year-old female developed HLH after immunization with the mRNA COVID-19 vaccine Comirnaty. Diagnosis was made according to HLH-2004 criteria; the HScore was 259 (> 99% HLH probability) with maximum ferritin of 138.244 µg/L. The patient was initially treated with intravenous immunoglobulins (IVIGs) and dexamethasone without response. The addition of the human interleukin 1 receptor antagonist Anakinra resulted in full recovery within 6 weeks after vaccination. A literature search revealed 15 additional cases of HLH after SARS-CoV-2 vaccination, the majority after immunization with Comirnaty (n = 7) or the viral vector vaccine Vaxzevria (n = 6). Treatment modalities included corticosteroids (n = 13), Anakinra (n = 5), IVIGs (n = 5), and etoposide (n = 2). Eight patients underwent combination treatment. Three of 16 patients died.

Conclusion: COVID-19 vaccines may occasionally trigger HLH, and Anakinra may be an efficacious treatment option for this condition.

Keywords: Hyperferritinemia; Hyperinflammation; Kineret; Lymphadenopathy; Macrophage activation syndrome; SARS-CoV-2 vaccine.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Cortex Hormones
  • Adult
  • COVID-19 Vaccines* / adverse effects
  • COVID-19* / prevention & control
  • Dexamethasone / therapeutic use
  • Etoposide
  • Female
  • Ferritins
  • Humans
  • Immunoglobulins, Intravenous
  • Interleukin 1 Receptor Antagonist Protein
  • Lymphohistiocytosis, Hemophagocytic* / diagnosis
  • Lymphohistiocytosis, Hemophagocytic* / drug therapy
  • Lymphohistiocytosis, Hemophagocytic* / etiology
  • RNA, Messenger
  • Receptors, Interleukin-1
  • SARS-CoV-2
  • Vaccination
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • COVID-19 Vaccines
  • Immunoglobulins, Intravenous
  • Interleukin 1 Receptor Antagonist Protein
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Etoposide
  • Dexamethasone
  • Ferritins