Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: Impact on disease course and in‐hospital mortality
Lei Zhang, Chaoqun Han, Shengyan Zhang, Caihan Duan, Haitao Shang, Tao Bai, Xiaohua Hou
Abstract
Abstract Background and Aim Dynamic changes of immunocyte subsets and inflammatory profiles in coronavirus disease 2019 (COVID‐19) patients with gastrointestinal symptoms were undetermined. Methods A single‐center retrospective analysis of 409 severe, hospitalized COVID‐19 patients from 20 January to 29 February 2020 was performed. The longitudinal characteristics of immune inflammatory cytokines in patients with/without diarrhea were analyzed. The relations of diarrhea and immuno‐inflammatory factors with illness course and clinical outcomes were further explored. Results Diarrhea was more common and more serious with longer duration (4.9 ± 1.5 vs 4.2 ± 1.5 days, P = 0.039) and higher frequency (5.5 ± 2.1 vs 4.0 ± 2.0 times/day, P = 0.001) in deceased patients than in the survivors. Also, diarrhea patients were more inclined to develop multi‐organ damage: survivors have longer illness course (media 41.0 vs 36.0 days, P = 0.052) and hospital stays (media 27.0 vs 23.0 days, P = 0.041), and the deceased patients had higher mortality (33.0% vs 22.6%, P = 0.045) and earlier death (media 20.0 vs 25.0 days, P = 0.038). Progressively, neutrophilia and lymphopenia, especially the declined CD8 + T cells, were demonstrated in diarrhea patients relative to the non‐diarrhea cases. The inflammatory cytokines including IL‐6, IL‐10, and TNF‐α were intensively increased in patients with diarrhea. The multivariable logistic analysis showed longer duration of diarrhea ( P = 0.036), higher neutrophil counts ( P = 0.011), and lower lymphocyte counts ( P < 0.001) were independent risk factors of in‐hospital death. The proportional hazards model indicated that longer duration of diarrhea ( P = 0.002), higher frequency of diarrhea ( P = 0.058), higher neutrophil counts ( P = 0.001), lower lymphocyte counts ( P = 0.035), and decreased proportion of CD8 + T cells ( P < 0.001) were independently associated with longer illness course of the survivors. Conclusions Diarrhea patients were more likely to present with neutrophilia, lymphopenia, and cytokine storm and to develop multi‐organ damage. The inflammatory patterns were independent factors associated with illness course of the survivors and in‐hospital death of severe COVID‐19.