Diarrhea and altered inflammatory cytokine pattern in severe COVID-19: impact on disease course and in-hospital mortality

Zhang, L.; Han, C.; Zhang, S.; Duan, C.; Shang, H.; Bai, T.; Hou, X.

BACKGROUND: 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 Jan 20 to Feb 29, 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 days vs 4 2 ± 1 5 days, P=0 039) and higher frequency (5 5 ± 2 1 times/day 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, who had longer illness course (media 41 0 days vs 36 0 days, P=0 052) and hospital stays (media 27 0 days vs 23 0 days, P=0 041) in survivors, and higher mortality (33 0% vs 22 6%, P=0 045) and earlier death (media 20 0 days vs 25 0 days, P=0 038) in the deceased patients 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 (P0 001) were independent risk factors of in-hospital death The proportional hazards model indicated 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 (P0 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