• Lin-Ling Cheng, Wei-Jie Guan, Chong-Yang Duan, Nuo-Fu Zhang, Chun-Liang Lei, Yu Hu, Ai-Lan Chen, Shi-Yue Li, Chao Zhuo, Xi-Long Deng, Fan-Jun Cheng, Yong Gao, Jian-Heng Zhang, Jia-Xing Xie, Hong Peng, Ying-Xian Li, Xiao-Xiong Wu, Wen Liu, Hui Peng, Jian Wang, Guang-Ming Xiao, Ping-Yan Chen, Chun-Yan Wang, Zi-Feng Yang, Jin-Cun Zhao, and Nan-Shan Zhong.
• State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
• JAMA Intern Med. 2021 Jan 1; 181 (1): 71-78.

ImportanceLymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19).ObjectiveTo 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 ParticipantsBetween 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.ExposuresUsual 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 MeasuresThe primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score.ResultsOf 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 RelevanceIn 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 RegistrationChinese Clinical Trial Registry: ChiCTR2000030007.

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