Hemophagocytic lymphohistiocytosis in COVID-19: Case reports of a stepwise approach

Medicine (Baltimore). 2021 Mar 26;100(12):e25170. doi: 10.1097/MD.0000000000025170.


Rationale: The immunologic syndrome induced by severe acute coronavirus disease 2019 (COVID-19) is yet not fully understood. Typical patterns of clinical and laboratory features match secondary hemophagocytic lymphohistiocytosis (sHLH). However, the optimal approach to COVID-19 patients testing positive for sHLH is still unclear.

Patient concerns: Three patients with COVID-19 are reviewed. All showed hyperinflammation and cytokine storm, necessitating intensive care treatment including mechanical ventilation.

Diagnosis: Secondary hemophagocytic lymphohistiocytosis due to severe COVID-19; diagnosed via HScore.

Interventions: A treatment regimen of methylprednisolone, pentaglobin, and anakinra was developed and administered.

Outcomes: One patient survived the ICU stay. Two other patients, in whom sHLH was diagnosed too late, deceased.

Lessons: A routine screening of COVID-19 patients for secondary HLH by using the HScore is feasible; especially those patients deteriorating clinically with no sufficient response to shock management might be at particular high risk. A stepwise therapeutic approach comprising corticosteroids, immunoglobulins and anakinra, accompanied by immunoadsorption, may dampen cytokine storm effects, and potentially reduce mortality.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • COVID-19 / complications*
  • COVID-19 / physiopathology
  • COVID-19 / therapy
  • Combined Modality Therapy
  • Critical Care
  • Cytokine Release Syndrome / drug therapy
  • Delayed Diagnosis
  • Fatal Outcome
  • Female
  • Humans
  • Immunoglobulin A / therapeutic use
  • Immunoglobulin M / therapeutic use
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Lymphohistiocytosis, Hemophagocytic / diagnosis
  • Lymphohistiocytosis, Hemophagocytic / drug therapy*
  • Lymphohistiocytosis, Hemophagocytic / etiology*
  • Male
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Respiration, Artificial
  • SARS-CoV-2


  • Anti-Inflammatory Agents
  • Immunoglobulin A
  • Immunoglobulin M
  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Interleukin 1 Receptor Antagonist Protein
  • pentaglobulin
  • Methylprednisolone