C Diff Associated with Increased Mortality in Patients with COVID-19


Patients with CDI and COVID-19 faced a higher risk of mortality and had higher CCI scores, a longer length of stay, and greater total hospital costs than patients infected with COVID-19 but not CDI.

Xheni Deda, MD | Credit: University of Missouri School of Medicine

Xheni Deda, MD

Credit: University of Missouri School of Medicine

A retrospective study of patients hospitalized with COVID-19 is providing an overview of the association between COVID-19 and Clostridioides difficile infection (CDI), highlighting several comorbidities as independent predictors of CDI in patients with COVID-19.

“While studies have indicated potential associations between COVID-19 and GI symptoms, the specific relationship between COVID-19 and CDI, as well as their combined impact on patient outcomes, remains poorly understood,” wrote investigators.1

According to the World Health Organization (WHO), over 760 million COVID-19 cases and 6.9 million COVID-19 related deaths have been recorded worldwide since December 2019. The most common symptoms are fever, chill, and sore throat, although the WHO also recognizes nausea, vomiting, abdominal pain and diarrhea as less common symptoms.2 This dysregulation of the immune response in the gastrointestinal tract can increase risk of coinfection with other gastrointestinal pathogens such as C. difficile, which frequently affects people with a weakened immune system.3

Led by Xheni Deda, MD, hepatology fellow at the University of Missouri, and a team of colleagues, the current study was launch with 2 aims: to examine the association between CDI and COVID-19 and to assess the impact of CDI on outcomes in patients with COVID-19. To do so, investigators collected data from the National Inpatient Sample (NIS) database for adult patients with a primary diagnosis of COVID-19 infection. Patients with a secondary diagnosis of CDI were also included. In total, investigators identified 1,045,125 COVID-19 hospitalizations and 4920 patients with a secondary diagnosis of CDI.1

The study population was divided into 2 groups based on CDI status. Investigators noted the COVID-19 and CDI group had a greater mean age (69.9 years) and more female patients (54.1%) compared to the COVID-19 without CDI group, which had a mean age of 64.2 years and was 47.1% female (P < 0.001).1

Investigators compared baseline characteristics, Charlson Comorbidity Index (CCI), and outcomes between the two groups using Chi-square and t-tests. Independent predictors of CDI and mortality were identified using multivariate logistic and linear regressions. Primary outcomes of interest were mortality and length of stay, while secondary outcomes included the cost of hospitalization, septic shock, acute liver failure, acute renal failure, and the need for mechanical ventilation.1

Upon analysis, 51.7% of patients in the CDI and COVID-19 group had a CCI score of 3 or more compared to 27.7% of patients without CDI (P < 0.001). Additionally, investigators noted the CDI and COVID-19 group had a longer length of stay (14.1 days vs 7.42 days; P < 0.001), greater total hospital costs ($42,336 vs $18,974; P < 0.001), and greater inpatient mortality (21.6% vs 11%; P < 0.001) compared to the COVID-19 group without CDI.1

Multivariate logistic regression analysis showed CDI was independently associated with increased mortality (odds ratio [OR], 1.37; P = 0.001). Investigators pointed out female gender, peptic ulcer disease, renal failure, weight loss, diabetes mellitus with complications, congestive heart failure, cardiac arrhythmias, liver disease, and non-metastatic solid organ tumors were associated with an increased risk of CDI. Peptic ulcer disease (OR, 2.3; 95% confidence interval [CI], 1.1-4.7) and renal failure (OR, 1.9; 95% CI, 1.6-2.4) showed the strongest association with CDI in COVID-19 patients.1

“Our study provides valuable insights into the incidence, outcomes, and risk factors of CDI in COVID-19 patients,” concluded investigators.1 “Our study raises important research questions for future investigations, including understanding the underlying mechanisms of increased CDI incidence in COVID-19 patients, exploring the role of medications and gut microbiota, and developing targeted interventions. Additionally, further research is needed to examine the impact of CDI on the clinical outcomes of COVID-19 patients, identify high-risk subgroups, and determine associated risk factors.”


  1. Deda X, Elfert K, Gandhi M, et al. Clostridioides difficile Infection in COVID-19 Hospitalized Patients: A Nationwide Analysis. Gastroenterology Research, 16(4). https://doi.org/10.14740/gr1639.
  2. World Health Organization. Coronavirus disease (COVID-19). Newsroom. August 9, 2023. Accessed September 13, 2023. https://www.who.int/news-room/fact-sheets/detail/coronavirus-disease-(covid-19)
  3. Centers for Disease Control and Prevention. What is C. diff? C. diff (Clostridioides difficile). Accessed September 13, 2023. https://www.cdc.gov/cdiff/what-is.html#:~:text=C.%20diff%20
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