Effect of Recombinant Human Granulocyte Colony–Stimulating Factor for Patients With Coronavirus Disease 2019 (COVID-19) and LymphopeniaA Randomized Clinical Trial

Question  Can treating patients with coronavirus disease 2019 (COVID-19) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) increase their peripheral blood leukocyte and lymphocyte cell counts and lead to clinical improvement?

Findings  In this open-label, randomized clinical trial of 200 Chinese patients with COVID-19, lymphopenia, and no comorbidities, rhG-CSF treatment did not accelerate clinical improvement, but the number of patients progressing to critical illness or death may have been reduced, without an increased risk of serious adverse events.

Meaning  Preliminary findings from a randomized clinical trial suggest that rhG-CSF treatment should be studied in larger trials and in a broader range of patients with COVID-19.

Importance  Lymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19).

Objective  To determine whether a therapy that increases peripheral blood leukocyte and lymphocyte cell counts leads to clinical improvement in patients with COVID-19.

Design, Setting and Participants  Between February 18 and April 10, 2020, we conducted an open-label, multicenter, randomized clinical trial at 3 participating centers in China. The main eligibility criteria were pneumonia, a blood lymphocyte cell count of 800 per μL (to convert to ×10⁹/L, multiply by 0.001) or lower, and no comorbidities. Severe acute respiratory syndrome coronavirus 2 infection was confirmed with reverse-transcription polymerase chain reaction testing.

Exposures  Usual care alone, or usual care plus 3 doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF, 5 μg/kg, subcutaneously at days 0-2).

Main Outcomes and Measures  The primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score.

Results  Of 200 participants, 112 (56%) were men and the median (interquartile range [IQR]) age was 45 (40-55) years. There was random assignment of 100 patients (50%) to the rhG-CSF group and 100 (50%) to the usual care group. Time to clinical improvement was similar between groups (rhG-CSF group median of 12 days (IQR, 10-16 days) vs usual care group median of 13 days (IQR, 11-17 days); hazard ratio, 1.28; 95% CI, 0.95-1.71; P = .06). For secondary end points, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (rhG-CSF group, 2% vs usual care group, 15%; difference, −13%; 95%CI, −21.4% to −5.4%). At 21 days, 2 patients (2%) had died in the rhG-CSF group compared with 10 patients (10%) in the usual care group (hazard ratio, 0.19; 95%CI, 0.04-0.88). At day 5, the lymphocyte cell count was higher in the rhG-CSF group (rhG-CSF group median of 1050/μL vs usual care group median of 620/μL; Hodges-Lehmann estimate of the difference in medians, 440; 95% CI, 380-490). Serious adverse events, such as sepsis or septic shock, respiratory failure, and acute respiratory distress syndrome, occurred in 29 patients (14.5%) in the rhG-CSF group and 42 patients (21%) in the usual care group.

Conclusion and Relevance  In preliminary findings from a randomized clinical trial, rhG-CSF treatment for patients with COVID-19 with lymphopenia but no comorbidities did not accelerate clinical improvement, but the number of patients developing critical illness or dying may have been reduced. Larger studies that include a broader range of patients with COVID-19 should be conducted.

Trial Registration  Chinese Clinical Trial Registry: ChiCTR2000030007