Delayed Neutropenia in Heart Transplant Recipients Following COVID-19 Diagnosis

INTRODUCTION: `Neutropenia is observed after heart transplantation due to medication effects and viral infections. SARS-CoV-2 infection, which causes Covid-19 illness, can uncommonly cause neutropenia in non-transplant recipients. Delayed neutropenia following SARS-CoV-2 infection in heart transplant recipients (HTRs) has not been described. CASE REPORT: Case 1: A 45 year old male combined heart and liver transplant recipient was diagnosed with Covid-19 17 months after transplant. Neutropenia had been noted six months after transplant in the setting of valganciclovir and mycophenolate mofetil (MMF) use, which resolved with discontinuation of those medications. At the time of his Covid-19 diagnosis, his immunosuppression regimen included tacrolimus with a target level 8-10 ng/mL and prednisone 5 mg once daily, and he had an asymptomatic course. His absolute neutrophil count (ANC) four weeks prior to Covid-19 diagnosis was 1,690/uL. The ANC obtained nine weeks after Covid-19 diagnosis was 890/uL. Testing for cytomegalovirus was negative and no neutrophil-depleting medications were identified. He received two doses of granulocyte colony stimulating factor (G-CSF). The subsequent ANC two days after the second dose was 3,600/uL. Case 2: A 66 year old male HTR was diagnosed with Covid-19 31 months after transplant. His symptoms included fever, cough, and diarrhea and he was admitted for inpatient care. Immunosuppression at the time of diagnosis included tacrolimus with a target level of 8-10 ng/mL and MMF 1000 mg twice daily, which was later decreased to 500 mg twice daily. The ANC nadir during his acute illness was 1310/uL. Six weeks after Covid-19 diagnosis, his ANC was 420/uL. Testing for cytomegalovirus was negative. The patient required a total of six doses of G-CSF over six weeks due to persistent neutropenia. MMF was discontinued. He was referred to a hematologist for persistent neutropenia. A bone marrow biopsy showed normal neutrophil production, and increased peripheral neutrophil consumption was hypothesized. SUMMARY: Acute viral infections including SARS-CoV-2 can cause neutropenia, but delayed neutropenia is rare and has not been described in HTRs. Careful monitoring of the complete blood count (with differential) may be useful in this population following a Covid-19 diagnosis. Modulation of immunosuppression and G-CSF administration can support neutrophil recovery.