Diarrhea and Altered Inflammatory Cytokine Pattern in Severe COVID-19: Impact on Disease Course and In-Hospital Mortality

J Gastroenterol Hepatol. 2020 Jun 29. doi: 10.1111/jgh.15166. Online ahead of print.

Abstract

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 (P<0.001) 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 (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.

Keywords: Coronavirus disease 2019; SARS-CoV-2; diarrhea; digestive system; immuno-inflammatory.