Diarrhea and altered inflammatory cytokine pattern in severe coronavirus disease 2019: Impact on disease course and in-hospital mortality

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 +/- 1.5vs4.2 +/- 1.5 days,P = 0.039) and higher frequency (5.5 +/- 2.1vs4.0 +/- 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 41.0vs36.0 days,P = 0.052) and hospital stays (media 27.0vs23.0 days,P = 0.041), and the deceased patients had higher mortality (33.0%vs22.6%,P = 0.045) and earlier death (media 20.0vs25.0 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-alpha 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.