Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection

Maslennikov, Roman; Svistunov, Andrey; Ivashkin, Vladimir; Ufimtseva, Anna; Poluektova, Elena; Efremova, Irina; Ulyanin, Anatoly; Okhlobystin, Alexey; Kardasheva, Svetlana; Kurbatova, Anastasia; Levshina, Anna; Grigoriadis, Diana; Magomedov, Shamil; Dzhakhaya, Natiya; Shifrin, Oleg; Zharkova, Maria; Yuryeva, Elena; Kokina, Nataliya; Shirtladze, Manana; Kiseleva, Olga

Diarrhea is one of the manifestations of the novel coronavirus disease (COVID-19), but it also develops as a complication of massive antibiotic therapy in this disease. This study aimed to compare these types of diarrhea. We included patients with COVID-19 in a cohort study and excluded patients with chronic diarrhea, laxative use, and those who died during the first day of hospitalization. There were 89 (9.3%), 161 (16.7%), and 731 (75.7%) patients with early viral, late antibiotic-associated, and without diarrhea, respectively. Late diarrhea lasted longer (6 [4–10] vs 5 [3–7] days, P < .001) and was more severe. Clostridioides difficile was found in 70.5% of tested patients with late diarrhea and in none with early diarrhea. Presence of late diarrhea was associated with an increased risk of death after 20 days of disease (P = .009; hazard ratio = 4.7). Patients with late diarrhea had a longer hospital stay and total disease duration, and a higher proportion of these patients required intensive care unit admission. Oral amoxicillin/clavulanate (odds ratio [OR] = 2.23), oral clarithromycin (OR = 3.79), and glucocorticoids (OR = 4.41) use was a risk factor for the development of late diarrhea, while ceftriaxone use (OR = 0.35) had a protective effect. Before the development of late diarrhea, decrease in C-reactive protein levels and increase in lymphocyte count stopped but the white blood cell and neutrophil count increased. An increase in neutrophils by >0.6 × 10(9) cells/L predicted the development of late diarrhea in the coming days (sensitivity 82.0%, specificity 70.8%, area under the curve = 0.791 [0.710–0.872]). Diarrhea in COVID-19 is heterogeneous, and different types of diarrhea require different management.