Results/Case Presentation
An 83-year-old Puerto Rican woman presented to the emergency department from a skilled nursing facility owing to generalized fatigue, weakness, and mechanical falls. On admission, the patient denied fever, chills, shortness of breath, chest pain, cough, nor sputum production. She was afebrile and hypotensive with a blood pressure of 90/50 mmHg. On physical examination, she appeared thin and chronically ill. She was alert and oriented only to self, which was reportedly her baseline state. Her initial lab work was remarkable for a hemoglobin 6.0 g/dL, mean corpuscular volume of 95.3 fL, white blood cell (WBC) count 5.8K/µL, and platelet count 351 K/µL. Her creatinine level of 2.50 mg/dL was elevated from her baseline of 1.30 mg/dL. Her past medical history was remarkable for dementia, primary myelofibrosis with macrocytic anemia and thrombocytosis, hypertension, chronic kidney disease stage III, and osteoporosis. She had a remote history of 40 pack years cigarettes. She had no history of chemotherapy, radiation, or chemical exposures. In October 2015, the patient was diagnosed with JAK2V617F positive PMF. Cytogenetic analysis revealed a normal karyotype. From diagnosis, the patient was treated with hydroxyurea 500 mg daily and aspirin 81 mg daily. She was dependent upon monthly packed red blood cell transfusions. Four months prior to hospitalization, treatment with ruxolitinib 20 mg daily was started.
Her admitting diagnosis was anemia secondary to primary myelofibrosis and acute kidney injury. She was transfused with two units of packed red blood cells. The following morning, she developed a mild non-productive cough and a fever of 101.2 ⁰F. Her oxygen saturation ranged between 90 to 92% on 2 liters of nasal cannula. Using a nasopharyngeal swab, the patient tested positive for SARS-CoV-2 by RT-PCR. RT-PCR results during her hospitalization are displayed in Table 1. Chest radiograph was unremarkable; procalcitonin was normal at 0.09 ng/mL. The following inflammatory markers were elevated: CRP 3.41 mg/dl, D-dimer 258 ng/mL, ferritin 1329 ng/mL, LDH 739 U/L, and fibrinogen 769 mg/dL (see Table 2). The patient was subsequently treated with hydroxychloroquine and azithromycin. Although the patient was largely asymptomatic, she remained an inpatient for the next four weeks as she was unable to be discharged back to her nursing home owing to persistently positive SARS-CoV-2 tests. Her persistently positive tests were attributed to immunosuppression from ruxolitinib causing the patient to have impaired viral RNA clearance. Nasal swab was tested for infectious virus by cytopathic effect in mammalian cell tissue culture (seeMethods ). No infectious virions were found. After discussing the risks and benefits with her family, ruxolitinib was discontinued. One day after stopping ruxolitinib, the patient developed a low-grade fever of 101.1⁰F and became hypoxic. Oxygen saturation ranged between 90-92% on room air. Her creatinine increased from 1.30 mg/d to 1.50 mg/d with leukocytosis ranging from 11 K/ul to 17 K/ul and thrombocytosis ranging from 450 K/ul to 550 K/ul. During this time, d-dimer, the only inflammatory marker measured, increased from 258 ng/mL on admission to 329 ng/mL, as depicted in Table 2. Chest radiograph was still unrevealing. Four days after stopping ruxolitinib, the patient was lethargic with increased urinary frequency. Subsequently, she was found to have a urine culture growing Enterococcus faecalis and she was treated with intravenous ampicillin and transitioned to oral amoxicillin for a total of 7 days of treatment. The patient did not receive ruxolitinib for five days total. After restarting ruxolitinib, the patient rapidly improved and was no longer febrile or hypoxic. Her WBC count decreased to 7.8 K/uL – 9.0 K/uL and platelet counts decreased to 424 K/uL – 540 K/uL. D-dimer was not re-measured. Following this brief drug holiday, the patient remained positive for SARS-CoV-2 by RT-PCR testing. She remained in isolation. She required two blood transfusions over the following two months. The decision to stop ruxolitinib for a second time was made in an attempt to give her immune system a second chance of eliminating the viral RNA. This time, the patient developed a mild cough with a leukocytosis ranging from 12.0 K/uL to 17.4 K/uL. Her platelet counts remained within normal limits. Ruxolitinib was discontinued for six days total and re-initiated due to the patient’s worsening clinical status. Despite this second trial off ruxolitinib, she was unable to achieve a negative PCR. Due to her persistently positive SARS-CoV-2 testing, the patient was given a 45-mcg subcutaneous injection of pegylated interferon α2a approved by the Veterans Affairs Hospital in hopes of facilitating viral RNA clearance. Three days following pegylated interferon administration, her RT-PCR test was still positive for SARS-CoV-2, and the patient was given weekly doses for a total of four doses. Ten days after receiving the second dose of pegylated interferon, the patient had a negative RT-PCR test. The patient did not experience any side effects from the pegylated interferon treatment. The patient ultimately cleared the viral RNA from nasal swabs on treatment with ruxolitinib with subcutaneous pegylated interferon (Table 1).