C Diff Deaths Increased During COVID-19 Pandemic, Study Finds


Findings revealed more than 5,000 excess deaths from CDI and 35.6% excess risk compared to the expected number of disease deaths calculated using data from the National Vital Statistics System.

Jinjun Ran, PhD | Credit: ResearchGate

Jinjun Ran, PhD

Credit: ResearchGate

Deaths from Clostridioides difficile infection (CDI) increased during the COVID-19 pandemic, according to findings from a study evaluating excess gastrointestinal, liver, and pancreatic disease deaths in the US.

Results showed more than 5,000 excess deaths from CDI, equating to 35.6% excess risk compared to the expected number of deaths during the study time frame.1

“Previous evidence has indicated patients with digestive-related abnormalities were vulnerable to the pandemic, not only because of their higher mortality risk of COVID-19, but their unmet healthcare needs due to the overwhelmed healthcare services,” wrote investigators.1 “However, few studies have quantified the impact of the pandemic on individuals with digestive diseases. There is also limited research examining the excess deaths associated with digestive diseases during the pandemic.”

The US Centers for Disease Control and Prevention estimates Clostridioides difficile causes almost 500,000 infections in the US each year, with severe cases requiring hospitalization.2 People who are immunocompromised, or whose immune system is weakened by medication, are more susceptible to serious illness from COVID-19, which may include those affected by gastrointestinal, liver, and pancreatic diseases.3 Beyond infection, the COVID-19 pandemic also stressed hospital systems and negatively affected health care and public health infrastructures, potentially limiting access to treatment for other illnesses.4

Jinjun Ran, PhD, associate professor at Shanghai Jiao Tong University School of Medicine in China, and a team of investigators sought to examine excess deaths related to gastrointestinal, liver, and pancreatic diseases during the COVID-19 pandemic by retrieving weekly provisional death counts from the National Vital Statistics System between January 2018 and February 2020, which provided investigators with information related to demographic information as well as cause of death. Using a quasi-Poisson regression model, investigators planned to estimate the expected deaths from March 2020 to September 2022.1

Investigators selected the dominant causes of death relevant to the digestive system, including gastrointestinal hemorrhage, ulcers, paralytic ileus and intestinal obstruction, vascular disorders of the intestine, Clostridium difficile colitis, esophageal cancer, gastric cancer, colorectal cancer, alcoholic liver disease, fibrosis/cirrhosis, chronic hepatitis C, hepatic failure, liver and intrahepatic bile duct cancer, acute pancreatitis, and pancreatic cancer. Excess death counts were calculated by subtracting expected death counts from observed death counts, excess mortality by excess death counts divided by population size, and excess risk by excess death counts divided by expected death counts.1

Both underlying and contributing causes of death assigned to digestive diseases were considered. Aggregated data were stratified by cause of death, age, sex, race, ethnicity, and state.1

Investigators noted the greatest excess death counts were 22,156 (95% confidence interval [CI], 21,478 to 22,504) for gastrointestinal hemorrhage, 17,531 (95% CI, 16,936 to 17,837) for alcoholic liver disease, and 10,741 (95% CI, 9930 to 11,157) for fibrosis/cirrhosis.1

CDI had the most significant increased death risk across all disease types (excess risk [ER], 35.9%; 95% CI, 34.1% to 37.8%). For gastrointestinal diseases, hemorrhage (ER, 24.8%; 95% CI, 24.0% to 25.5%), ulcers (ER, 15.1%; 95% CI, 13.6% to 16.7%), and colorectal cancer (ER, 3.4%; 95% CI, 2.9% to 3.9%) also had notable death risks. For liver and pancreatic diseases, acute pancreatitis had the largest ER (20.6%, 95% CI, 18.9% to 22.4%), followed by alcoholic liver disease (19.9%, 95% CI, 19.2% to 20.6%), chronic hepatitis C (15.1%, 95% CI, 13.9% to 16.3%), fibrosis/cirrhosis (8.5%, 95% CI, 7.9% to 9.1%), and hepatic failure (7.1%, 95% CI, 6.4% to 7.9%).1

Investigators pointed out ERs for gastrointestinal diseases were higher among adults aged 20-64 years compared to adults aged 65-84 years, particularly for gastrointestinal hemorrhage (38.7% vs 26.2%), ulcers (23.4% vs 9.8%), and CDI (54.7% vs 39.6%). Higher ERs of liver disease were also more prevalent among young adults, including alcoholic liver disease (23.0% vs 15.9%), fibrosis/cirrhosis (16.0% vs 6.8%), and hepatic failure (13.0% vs 4.6%).1

Investigators also noted disproportional ERs were observed upon stratification by race and ethnicity. The ER of CDI was 49.2% (95% CI, 42.8% to 55.7%) among non-Hispanic Blacks, −0.2% (95% CI, −5.5% to 5.4%) among Hispanic participants, and 37.2% (95% CI, 35.1% to 39.4%) among non-Hispanic Whites. The ERs of alcoholic liver disease in non-Hispanic Blacks, Hispanics, and non-Hispanic Whites were 27.4%, 23.6%, and 16.8%, respectively. The ERs in Hispanics and non-Hispanic Whites were 27.1% and 14.0%, respectively, for chronic hepatitis C, 23.6% and 7.2%, respectively, for fibrosis/cirrhosis, and 13.4% vs. 6.7%, respectively, for hepatic failure.1

The ERs of most gastrointestinal, liver, and pancreatic diseases were more pronounced in Wave II and highest in Wave IV, which were defined by investigators as June 2020 to October 2020 and June 2021 to November 2021, respectively. Of note, CDI showed a persistently increasing trend throughout the entire pandemic.1

“As SARS-CoV-2 may continually circulate in the community and lead to potential epidemic waves in the future, it is important for pertinent stakeholders to further evaluate the long-term impact of the pandemic on healthcare workers and patients,” investigators concluded.1 “It is also necessary to develop sustainable strategies to improve the diagnostic, treatment, and disease management capacities of patients with GI, liver, and pancreatic conditions in the era of living with COVID-19.”


  1. Han L, Shi H, Li Y, et al. Excess Deaths of Gastrointestinal, Liver, and Pancreatic Diseases During the COVID-19 Pandemic in the United States. Int J Public Health 68:1606305. doi:10.3389/ijph.2023.1606305
  2. Centers for Disease Control and Prevention. What is C. diff? C. diff (Colstridioides difficile). Accessed September 26, 2023. https://www.cdc.gov/cdiff/what-is.html
  3. Centers for Disease Control and Prevention. Factors That Affect Your Risk of Getting Very Sick from COVID-19. COVID-19. May 11, 2023. Accessed September 26, 2023. https://www.cdc.gov/coronavirus/2019-ncov/your-health/risks-getting-very-sick.html
  4. Centers for Disease Control and Prevention. Impact of Hospital Strain on Excess Deaths During the COVID-19 Pandemic — United States, July 2020–July 2021. Morbidity and Mortality Weekly Report. November 19, 2021. Accessed September 26, 2023. https://www.cdc.gov/mmwr/volumes/70/wr/mm7046a5.htm
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