Abstract | Importance: 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: 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.
|
Authors | 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, Nan-Shan Zhong |
Journal | JAMA internal medicine
(JAMA Intern Med)
Vol. 181
Issue 1
Pg. 71-78
(01 01 2021)
ISSN: 2168-6114 [Electronic] United States |
PMID | 32910179
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Adrenal Cortex Hormones
- Anti-Bacterial Agents
- Antiviral Agents
- Hematologic Agents
- Recombinant Proteins
- Granulocyte Colony-Stimulating Factor
|
Topics |
- Adrenal Cortex Hormones
(therapeutic use)
- Adult
- Anti-Bacterial Agents
(therapeutic use)
- Antiviral Agents
(therapeutic use)
- B-Lymphocytes
- CD4 Lymphocyte Count
- COVID-19
(blood, complications, physiopathology)
- China
- Disease Progression
- Female
- Granulocyte Colony-Stimulating Factor
(therapeutic use)
- Hematologic Agents
(therapeutic use)
- Hospital Mortality
- Humans
- Killer Cells, Natural
- Leukocyte Count
- Lymphocyte Count
- Lymphopenia
(blood, complications, drug therapy)
- Male
- Middle Aged
- Mortality
- Noninvasive Ventilation
- Oxygen Inhalation Therapy
- Recombinant Proteins
- Respiratory Distress Syndrome
(physiopathology)
- Respiratory Insufficiency
(physiopathology)
- SARS-CoV-2
- Sepsis
(physiopathology)
- Shock, Septic
(physiopathology)
- Time Factors
- COVID-19 Drug Treatment
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|