P2127 - Clostridioides difficile in Patients With Inflammatory Bowel Disease After SARS-CoV-2 Infection: A Multi-Site Retrospective Cohort Study From the National COVID Cohort Collaborative (N3C)

Monday, October 23, 2023

10:30 AM – 4:15 PM PT

Location: Exhibit Hall

Presenting Author(s)

Sara Ghoneim, MD

University of Nebraska Medical Center
Omaha, NE

Sara Ghoneim, MD¹, Makayla Schissel, MPH¹, Jerrod Anzalone, MS¹, Nabil El-hage Chehade, MD², Peter Mannon, MD, MPH¹
¹University of Nebraska Medical Center, Omaha, NE; ²Scripps, La Jolla, CA

Introduction: Patients with inflammatory bowel disease (IBD) are at an increased risk of developing Clostridioides difficile infection (CDI). Aim: to assess the risk of CDI in IBD patients after SARS-CoV-2 infection.

Methods: We conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients with SARS-CoV-2 infection in the USA, between Jan 1, 2020 and May 18, 2023. Descriptive statistics were used to summarize the demographic, clinical, and outcome characteristics of patients with and without IBD. Patients having CDI 6 months prior to their positive COVID-19 test or diagnosis were excluded. Multivariable Cox regression models were used to determine the risk of experiencing CDI within 28 days of a positive COVID-19 test or diagnosis. Additional regression models stratifying by the presence or absence of IBD were conducted for comparison.

Results: Out of 5,978,435 patients with COVID-19, 43,751 were diagnosed with IBD (Table). After adjusting for demographic differences and background risk (Figure), a history of IBD was associated with the highest risk of CDI after COVID-19 diagnosis, (adjusted hazard ratio (aHR): 3.76, 95% confidence interval: (CI): 3.26-4.33). This was followed by diagnosis of CKD (aHR 2.95, 2.74-3.17), antibiotic use in the past 6 months (aHR 2.73, 2.53-2.93), or organ/stem cell transplant (aHR 2.22, 1.90-2.60). Vaccination with 2 or 3 doses of COVID-19 vaccines was protective against CDI (aHR 0.59, 0.52-0.66; aHR 0.47, 0.41-0.53, respectively). Among those with IBD, patients with CKD had the highest risk of CDI (aHR 2.16, 1.56-3.00) after SAR-CoV-2 infection, followed by IBD patients with antibiotic use in the past 6 months (aHR 2.04, 1.49-2.77) or with a concurrent diagnosis of CHF (aHR 1.78, 1.20-2.65). Significant associations were observed between the use of biologics, immunomodulators, or steroids and CDI between IBD and non-IBD patients (Table). Completion of primary vaccination series was protective against CDI (aHR 0.46, 0.27-0.80) after 3 doses but not with 2 doses (aHR 0.83, 0.53-1.30).

Discussion: This data suggests that IBD patients with SARS-CoV-2 infection have a high risk of CDI within 28 days of COVID-19 diagnosis. The risk is highest in those with CKD or prior antibiotic use. The concomitant use of prednisone and especially thiopurines and biologics were associated with significantly increased rates of CDI compared to use of these drugs in non-IBD patients.

Figure: Figure. Adjusted hazard ratios for Clostridioides difficile infection (CDI) within 28 days post COVID-19 diagnosis in patients with inflammatory bowel disease. Patients who received 2 doses in the primary vaccination series with a COVID-19 diagnosis are considered "VAX2 breakthrough infection" while those that received the primary vaccination series and an additional booster dose are considered "VAX3 breakthrough infection.

Abbreviations: aHR, adjusted hazard ratio; CKD, chronic kidney disease; CHF, congestive heart failure; CAD, coronary artery disease.

Characteristic¹	Overall N = 5,979,435	Non IBD N = 5,935,684		IBD N = 43,751	p value²
Sex					< 0.001
Female	3,390,048 (57%)	3,364,378 (57%)		25,670 (59%)
Male	2,589,387 (43%)	2,571,306 (43%)		18,081 (41%)
Age	46 (32, 61)	46 (32, 61)		50 (36, 64)	< 0.001
Age Strata					< 0.001
18-49	3,299,131 (55%)	3,277,759 (55%)		21,372 (49%)
50-64	1,490,544 (25%)	1,478,743 (25%)		11,801 (27%)
65+	1,189,760 (20%)	1,179,182 (20%)		10,578 (24%)
Race/Ethnicity					< 0.001
White	3,714,544 (62%)	3,680,254 (62%)		34,290 (78%)
Black or African American	795,452 (13%)	791,434 (13%)		4,018 (9.2%)
Hispanic or Latino	685,556 (11%)	683,200 (12%)		2,356 (5.4%)
Other/Unknown	783,883 (13%)	780,796 (13%)		3,087 (7.1%)
Comorbidities
Current or Former Smoker	239,187 (4.0%)	235,714 (4.0%)		3,473 (7.9%)	< 0.001
Chronic Kidney Disease	368,154 (6.2%)	362,338 (6.1%)		5,816 (13%)	< 0.001
Hypertension	1,563,796 (26%)	1,546,251 (26%)		17,545 (40%)	< 0.001
Diabetes Mellitus	739,492 (12%)	732,262 (12%)		7,230 (17%)	< 0.001
Congestive Heart Failure	185,705 (3.1%)	183,094 (3.1%)		2,611 (6.0%)	< 0.001
Coronary Artery Disease	355,514 (5.9%)	350,911 (5.9%)		4,603 (11%)	< 0.001
Cancer (any malignancy except skin)	367,128 (6.1%)	361,234 (6.1%)		5,894 (13%)	< 0.001
Solid Organ or Bone Marrow Transplant	16,377 (0.3%)	15,988 (0.3%)		389 (0.9%)	< 0.001
Obesity	1,792,136 (30%)	1,774,625 (30%)		17,511 (40%)	< 0.001
Inflammatory Bowel Disease Type					< 0.001
Ulcerative Colitis	18,279 (0.3%)	N/A		18,279 (42%)
Crohn’s Disease	22,132 (0.4%)	N/A		22,132 (51%)
Antibiotic use in the past 6 months	229,521 (3.8%)	224,823 (3.8%)		4,698 (11%)	< 0.001
Immunosuppression Drugs
Prednisone	807,932 (14%)	791,234 (13%)		16,698 (38%)	< 0.001
Thiopurine	16,764 (0.3%)	11,833 (0.2%)		4,931 (11%)	< 0.001
Biologics	31,016 (0.5%)	19,844 (0.3%)		11,172 (26%)	< 0.001
biologics
Immunosuppression Drug Groups					< 0.001
Biologic Only	13,187 (0.2%)	8,984 (0.2%)		4,203 (9.6%)
Biologic/Prednisone	14,523 (0.2%)	10,208 (0.2%)		4,315 (9.9%)
Biologic/Thiopurine	2,054 (< 0.1%)	474 (< 0.1%)		1,580 (3.6%)
Biologic/Prednisone/Thiopurine	1,252 (< 0.1%)	178 (< 0.1%)		1,074 (2.5%)
Other immunosuppression Drug Combination	5,948,419 (99%)	5,915,840 (100%)		32,579 (74%)
Vaccination Status Before COVID-19					< 0.001
No Documented COVID-19 Vaccinations	5,112,228 (85%)	5,077,318 (86%)		34,910 (80%)
Primary Vaccination Series	478,940 (8.0%)	474,718 (8.0%)		4,222 (9.7%)
Primary Vaccination Plus Booster Series	388,267 (6.5%)	383,648 (6.5%)		4,619 (11%)
C. difficile 28-Days Post-COVID-19	4,666 (< 0.1%)	4,429 (< 0.1%)		237 (0.5%)	< 0.001
Among those with C. difficile³
COVID-19 Vaccinated (Primary or Primary +)⁴	528 (11%)	493 (11%)	35 (15%)		0.12
Prednisone	1405 (30%)	1301 (29%)	104 (44%)		< 0.001
Thiopurine	83 (1.8%)	63 (1.4%)	20 (8.4%)		< 0.001
Biologics	82 (1.8%)	23 (0.5%)	59 (25%)		< 0.001

Disclosures:

Sara Ghoneim indicated no relevant financial relationships.

Makayla Schissel indicated no relevant financial relationships.

Jerrod Anzalone indicated no relevant financial relationships.

Nabil El-hage Chehade indicated no relevant financial relationships.

Peter Mannon indicated no relevant financial relationships.

Sara Ghoneim, MD¹, Makayla Schissel, MPH¹, Jerrod Anzalone, MS¹, Nabil El-hage Chehade, MD², Peter Mannon, MD, MPH¹. P2127 - Clostridioides difficile in Patients With Inflammatory Bowel Disease After SARS-CoV-2 Infection: A Multi-Site Retrospective Cohort Study From the National COVID Cohort Collaborative (N3C), ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.