ABSTRACT
Background: Immune reconstitution inflammatory syndrome (IRIS) is a rapid inflammatory response with immune recovery, most commonly observed following antiretroviral therapy initiation in people with HIV and underlying opportunistic infections. To date there is one reported case of COVID-associated IRIS in a neutropenic patient treated with granulocyte colony-stimulating factor (G-CSF). Here we describe a second case of COVID-associated IRIS in a patient with history of follicular lymphoma who received G-CSF during acute COVID-19 infection. Case: A 64-year-old woman with history of follicular lymphoma and autologous stem cell transplant one year prior presented with dyspnea, diarrhea, and fever, and tested positive for SARS-CoV-2. She had received three doses of the Pfizer BioNTech vaccine. She was admitted to the hospital for acute hypoxic respiratory failure and treated with remdesivir 100mg, dexamethasone 6mg, and 2 L/min supplemental oxygen via nasal cannula for five days. Twelve days after discharge, the patient returned with persistent diarrhea, fatigue, fever, and an oxygen saturation of 87% on room air. She again tested positive for SARS-CoV-2 by PCR. She was admitted to the intensive care unit for high-flow nasal cannula (HFNC) with oxygen at 30 L/min and 50% FiO2 and treated with methylprednisolone 1 mg/kg daily. On admission, her D-dimer was 3943 ng/mL, C-reactive protein 136 mg/L, absolute neutrophil count (ANC) 767/mcL, platelets 84/mcL. Her chest CT scan was negative for pulmonary embolism but demonstrated bilateral ground glass opacities characteristic of COVID-19 pneumonia. Her ANC reached a nadir of 186 on day 3 at which point G-CSF (filgrastim 300 mcg/day) was administered for three days with subsequent neutrophil recovery. On day 6, in light of a negative test for COVID antibodies, she received high-dose monoclonal antibodies through a compassionate use program. At that time, her oxygen requirements were stable and inflammatory markers had decreased to CRP 25 and D-Dimer 940. However, her oxygen requirements and inflammatory markers rapidly increased thereafter, with HFNC settings up to 60L/80%, D-dimer 27754, and CRP 135. After a repeat chest CT on day 8 showed worsened ground glass opacities throughout all lung fields, her steroid dose was increased to methylprednisolone 2 mg/kg daily out of concern for COVID-associated IRIS following G-CSF administration. Her oxygen requirement and inflammatory markers declined over the following 2-3 days and she was transferred out of the ICU. Discussion: We present here an unusual case of COVID-associated IRIS after G-CSF administration in a transplant patient with COVID-19 pneumonia. Given the increased risk of infection and severe illness in immunosuppressed patients despite vaccination, it is important for providers to be aware of complications associated with adjunct therapies such as G-CSF in this vulnerable population.
ABSTRACT
Introduction: The Grady Comprehensive Sickle Cell (SC) center is the largest adult sickle cell center in the United States (US) and has the first 24/7 acute care unit for management of sickle cell vaso-occlusive events (VOE). In 2019, the center provided 3077 sickle cell outpatient visits and 3695 acute care visits. When the COVID-19 pandemic reached the US, the center had a precipitous drop in the number of both outpatient clinic and acute care visits as state regulations for lockdown were passed. This report follows all the COVID-19 cases at a single adult center for sickle cell disease in one year. Methods: The clinical database has been tracking COVID-19 cases reported. Out of a total of 1343 patients, 55 patients contracted COVID-19 and were tracked in the clinical database with IRB approval. Results: Of the 55 patients with COVID-19, 28 were female and 27 were male. By genotype, 64% of patients were SS, 31% were SC and 5% were Sβ+ thalassemia. 35% of patient were on hydroxyurea for disease modification with the majority of them being of the SS genotype and 31% had elevated fetal hemoglobin determined by a percentage fetal hemoglobin above 5% by hemoglobin electrophoresis. Chronic pain (defined as patients experiencing daily pain episodes for more than 4 days a week for the last 3 months) and calculation of daily morphine equivalents were reported in clinic follow-up and the narcotic database utilization. 47% of the patients had chronic pain and the median morphine equivalents was 90 mg daily (45-225mg). The rate of emergency department (ED) visits or hospitalizations for the sickle cell patients with COVID-19 was 80%. 49% of the SC patients' visits were related to VOE and 27% related to COVID-19 primarily. 20% of SC patients with COVID-19 were not seen in any emergency setting or required any hospitalization. The COVID-19 signs and symptoms experienced by the patients were as follows: 58% had pain as the main presenting symptom, followed by cough and fever (40%), dyspnea (31%), and pneumonia with chest x-ray evidence (25%). 2 patients developed acute respiratory distress syndrome (ARDS) and were intubated, and 2 patients died. 29% of the patients had lung findings on imaging and 16 of 55 patients required treatment with the use of Remdesivir in 9, dexamethasone in 8 and red cell products in 7 of the 16 patients. The 2 patients who died had both presented with COVID-19 infection in June and July 2020 respectively. One patient had presented in June 2020 with VOE and was found to have bilateral lung opacities but was asymptomatic and was discharged home to return few days later with clinical picture of multi-organ failure for which a red cell erythrocytapheresis was attempted. The second patient had presented in July 2020 with COVID-19 pneumonia and was treated with Remdesivir and convalescent plasma with development of multi-organ failure and ARDS. Discussion: Several reports were published regarding the rate of COVID-19 related mortality and morbidity in sickle cell disease. The Grady comprehensive sickle cell center experience differs in the fact that 16 out of 55 patients who had contracted COVID-19 required treatment and 2 of those 16 had died. In fact, the deaths occurred early in the course of the pandemic in June and July 2020 when 20 total cases were diagnosed (from March to Septemeber 2020). The remaining 35 cases registered zero deaths (October 2020 to March 2021) with the rate of complicated COVID-19 hospitalizations decreasing with better treatment available. In addition, the timeline for the COVID-19 cases reported fits the population timeline of 2 peaks respectively happening in the summer of 2020 and the Winter of 2021. During the initial peak, we have noted a decrease in the number of clinic and acute care visits respectively. This was anticipated given the statewide lockdown that was implemented. To circumvent that, the center adopted virtual visits to deliver healthcare needs. This measure has aided in protecting patients against COVID-19. Additionally, it is interesting that despite the seco d peak in the winter of 2021, there were no reported deaths among the patients who developed COVID-19. This finding can suggest that despite the concern for morbidity and mortality of sickle cell patients, their diligence and awareness to stay home during the pandemic has proven crucial in reducing morbidity and mortality and the option of virtual visits for healthcare delivery was key and should be utilized further in sickle cell care. [Formula presented] Disclosures: No relevant conflicts of interest to declare.