Hemophagocytic Lymphohystiocytosis in a Patient with Post-Acute COVID-19 Infection

Introduction: Hemophagocytic lymphohistiocytosis [HLH] is characterized by immune dysregulation with extensive inflammation and tissue destruction due to abnormal immune activation. Although primary HLH is commoner in the pediatric population, secondary HLH [sHLH] is more typical in adults, with underlying associations such as hematologic malignancy, infections or rheumatologic conditions.

COVID-19 infection has been associated with immune dysregulation syndromes such as cytokine storm as well as HLH. However, post COVID-19 patients who have recovered with negative serologic tests may also present with sHLH, an unusual finding which our case demonstrates.

Case report: A 73-year-old male with a notable past medical history of fall COVID-19 infection approximately 11 months prior presented initially to emergency services with a chief complaint of high fevers, lethargy and progressive changes in mentation gradually progressive over the last 5 months duration. Initial work-up for sources of infection including testing for atypical infections and imaging investigations were unrevealing. Laboratory investigations were remarkable initially for transaminitis, elevated LDH, anemia and thrombocytopenia. Coagulation panel revealed prolonged APTT and PT with low fibrinogen. Ferritin level was markedly elevated.

This presentation was concerning for hemophagocytic lymphohistiocytosis. The patient did have a bone marrow biopsy two months prior to presentation which was unremarkable for hematologic malignancy or features suggestive of HLH such as hemophagocytosis.

In view of the patient's high H score and clinical suspicion for HLH, he was initiated on dexamethasone 20 mg daily. Cryoprecipitate and platelet transfusions were administered for correction of coagulopathy. Over the course of the hospitalization, WBC count continued to drop with critically low absolute neutrophil counts prompting initiation of Filgrastim.

No noticeable clinical improvement was noted over the subsequent days of hospitalization, and the patient was subsequently trialed on an intravenous immunoglobulin protocol for 3 days.

Despite all treatment offered, the patient continued to deteriorate and after consultation with family members and the palliative care team, patient was transitioned to comfort measures only and code status was changed to DNR/DNI. The patient subsequently passed away a few days later.

Conclusion: sHLH following COVID-19 infection, although previously described, remains a poorly understood phenomenon. Even more puzzling is why certain patients develop a delayed sHLH following postacute COVID-19 illness. Notably, the severity of the COVID-19 infection does not appear to be related to one's predisposition to develop sHLH. Regardless of etiology, the mortality of HLH remains high even with appropriate therapy, especially with neurologic involvement and markedly elevated ferritin levels.

No relevant conflicts of interest to declare.