Case Presentation: We present a case of rapidly progressive Hypereosinophilic Syndrome (HES), a possible late complication of Sars-CoV-2 (COVID-19). A previously healthy 48-yr old male recovered from COVID-19 approximately 30 days before symptom onset. He had fevers, chills, diffuse abdominal pain with nausea, vomiting, and diarrhea with diffuse erythematous pruritic rash and Raynaud’s phenomenon (Image 1). The persistent symptoms resulted in repeated hospitalizations over a month. Work up revealed negative COVID-19 PCR test but positive COVID IgG. Over 14 days he developed rapidly progressive eosinophilia with absolute eosinophil count (AEC) rising from 2.63 × 10^9/L to 36.33 × 10^9/L (0.05-0.5 × 10^9/L), (Image 2). Drug-induced eosinophilia was ruled out. He failed a trial of empiric Ivermectin. Normal hemoglobin, platelet count, renal function, electrolytes and mild transaminitis were seen. Further work up had negative Influenza Ag, HIV screen, stool culture & ova/parasite, blood culture and unremarkable CSF analysis/culture. He had negative Toxocara, Strongyloides and Trichinella serology and negative ANA, cANCA, but + RF. Serum IgE was elevated at 547 ku/L (0-150 ku/L). EGD and colonoscopy with biopsies was diagnostic for esophageal and diffuse colon chronic inflammation with increased intramucosal eosinophils. Bone marrow biopsy had prominent eosinophils, but otherwise unremarkable along with T cell clonal analysis and flow cytometry. Serum Tryptase and B12 level was normal. FISH ruled out BCR/ABL1 or FIP1L1/PDGFRA gene fusions, or PDGFRA, PDGFRB, FGFR1, JAK2 gene rearrangement. CT head, chest, abdomen and pelvis and brain MRI diagnostic only for changes suggestive of gastroenteritis. TTE with normal LVEF and valve function. Findings and clinical symptoms met the diagnostic criteria of idiopathic Hypereosinophilic Syndrome (iHES). Patient had a dramatic clinical response to high dose steroids with resolution of eosinophilia and symptoms.
Discussion: HES is a rare multisystem disease characterized by peripheral blood AEC > 1.5 × 10^9/L with eosinophil-mediated organ damage and absence of an alternative explanation for the observed organ pathology. The most common organs involved are integumentary (69%), pulmonary (44%), and GI (38%). HES-related complications include arterial and venous thrombosis and cardiac involvement accounting for majority of mortality. HES has monoclonal, secondary, and idiopathic subtypes and must be differentiated for appropriate treatment regimen. Corticosteroids (0.5-1 mg/kg/day) are highly effective at inducing remission for iHES. Steroid-refractory cases may respond to cytotoxic agents, immunomodulators or to monoclonal anti-IL-5 antibody. COVID-19 infection leads to complex immune system activation. Eosinophils participate in defense against viral pathogens by modulating CD8+ T-cell proliferation/activation and by their nuclease enzymatic activity. Several eosinophil-associated complications of COVID-19 have been reported, including pulmonary eosinophilic vasculitis and eosinophilic myocarditis signaling the potential role of eosinophils in COVID-19 complications.
Conclusions: Health care providers should be on alert for potential eosinophil-related COVID-19 complications. Persistent eosinophilia with multiorgan symptomatology should raise suspicion for HES. Timely diagnostic and therapeutic interventions are important to halt disease progression and achieve remission.