G-CSF IN COVID-19 PATIENTS: INCREASED NEED FOR MECHANICAL VENTILATION AND INFERIOR 60-DAY SURVIVAL

ABSTRACT

Introduction Granulocyte colony stimulating factor (G-CSF) is a crucial supportive care medication, used for the prevention of febrile neutropenia in patients undergoing chemotherapy. Early in the COVID-19 pandemic, experts began discussing whether increased use of G-CSF in cancer patients and the minimization of the neutropenic period could provide benefit in that patient population. Concerns were soon raised, however, regarding the potential synergy between the pro-inflammatory COVID-19 disease process and immune stimulation from G-CSF administration. It was noted that COVID-19 patients exposed to G-CSF were developing markedly elevated Neutrophil to Lymphocyte Ratios (NLR), indicating an excessive inflammatory response and an increased risk of ARDS and inhospital mortality. The purpose of this study is to better understand the potential harm caused by this synergy. Methods We used TriNetX, a global health research network providing access to electronic medical records from approximately 85 million patients in 64 large healthcare organizations. The platform only contains de-identified data as per the de-identification standard defined in Section 164.514(a) of the HIPAA Privacy Rule. SARS-CoV-2 infection was determined by laboratory codes 9088, 94309-2, and 94500-6, indicating the presence of COVID-19 RNA. Use of G-CSF was determined by J-code J1442, indicating its administration through having been billed to the patient. Two neutropenic (ANC <1,000/microliter) cohorts were then generated, one having COVID-19 infection and G-CSF administration within the subsequent 2 weeks, and the other with COVID-19 infection and no G-CSF administration. Both cohorts were balanced for age, gender, race, and ethnicity. Most importantly, the cohorts were balanced for average initial neutrophil count to rule out the potential sampling error of more severely neutropenic patients having worse outcomes. These criteria resulted in cohorts of 715 patients each. The cohorts were then evaluated for the outcome of “ventilation assist and management, initiation of pressure or volume preset ventilators for assisted or controlled breathing” via procedure code 1014859. Results Patients who received G-CSF within 2 weeks following COVID-19 infection were 3.7 times more likely to end up on a ventilator (p<0.0001), and had 3.5 times greater 60-day mortality (6.557% vs 1.878%, p<0.0001). Conclusions SARS-CoV-2 infection is associated with a significant inflammatory response, and the use of G-CSF in neutropenic patients within 2 weeks of infection is associated with a significant increased risk of need for mechanical ventilation and increased risk of 60-day mortality. Use of G-CSF in this patient population should be discouraged in favor of broadspectrum antibiotic coverage.