Clostridioides difficile Outcomes in Patients With COVID-19 Were Stable Across Four Waves of the Pandemic

Introduction: The COVID-19 (C19) pandemic caused unprecedented disruptions in our healthcare system. Clostridioides difficile infection (CDI) is associated with antibiotic use and hospitalization which were both seen uniquely during C19 infection waves. Each wave saw a different SARS-CoV-2 strain with varying virulence. We hypothesized that with the changing virulence during separate spikes of infection, rates of CDI and outcomes would vary. Methods: We performed a retrospective analysis of all adult patients (≥18) admitted to Yale-New Haven Hospital from March 17, 2020 to March 10, 2022 diagnosed with both CDI and C19 during the same admission. Discrete C19 waves were identified, where a wave was defined as a period of time with ≥30 C19 patients admitted to the hospital in a single day. The cohorts were compared for demographics, comorbidities, recent hospitalizations and outcomes (90-day recurrence, readmission and mortality). Additionally, CDI outcomes were compared across all waves against a pre-pandemic cohort of all CDI admissions during 2019. Results: Four waves of C19 elapsed from 3/17/20 to 3/10/2022. A total of 70 patients were identified diagnosed with both CDI and C19 during the same admission across all 4 waves, with 18, 27, 5 and 20 in the first, second, third and fourth waves, respectively. 36 (51.4%) were male with a median age of 69 (IQR: 58-78). Comparing CDI outcomes across waves, there were no statistically significant differences in 90-day CDI recurrence, 90-day readmission, or 90-day mortality. Comparing all cases of CDI and C19 across all 4 waves against a pre-pandemic cohort from 2019, there was a higher 90-day readmission rate in 2019 compared with during the pandemic (48.7% vs 32.9%; P = 0.015). Results are summarized in Table 1. Conclusion: 90-day CDI recurrence, readmission and mortality did not differ across 4 waves of the pandemic in patients diagnosed with both CDI and C19. Despite differences in virulence of viral strains, evolving treatment protocols (including potential heavier antibiotic use in the earlier phases) and availability of effective vaccines, CDI outcomes remained stable. Our study is limited by small sample size. Interestingly, 90-day readmissions were higher pre-pandemic. This could potentially be explained by better infection control and antimicrobial stewardship, but warrants further study. Subsequent investigation should also determine whether CDI rates and outcomes in all CDI patients regardless of COVID status varied during and between waves. Table 1. - Baseline Characteristics and Outcome Comparison During Different COVID-19 Waves and Comparison With Historic Pre-pandemic Group in 2019 Outcome Patients who had CDI and COVID-19 during the same admission Wave 1 n = 183/17/2020 - 6/20/2020 Wave 2 n = 2710/15/2020 - 5/18/2021 Wave 3 n = 58/7/2021 - 9/28/2021 Wave 4 n = 2011/24/2021 - 3/10/2022 TotalN = 70 Age (years), median [IQR] 70 [58-78] 71 [58-75] 69 [60-78] 65.5 [54.5-80.5] 69 [58-78] Female, n (%) 7 (38.89) 12 (44.44) 2 (40.00) 13 (65.00) 34 (48.57) BMI, mean ± SD 27.89 ± 6.13 27.57 ± 6.41 29.05 ± 7.02 27.27 ± 5.77 27.67 ± 6.08 Charlson co-morbidity index, mean ± SD 6 ± 2.32 6.5 ± 3.34 6.4 ± 1.52 4.7 ± 3.03 5.8 ± 2.95 Admission within the last 3 months, n (%) 8 (44.44) 14 (51.85) 2 (40.00) 8 (40.00) 32 (45.71) Mechanical ventilation, n (%) 4 (22.22) 9 (33.33) 2 (40.00) 4 (20.00) 19 (27.14) 90-Day CDI Recurrence, n (%) 1 (5.56) 4 (14.81) 1 (20.00) 1 (5.00) 7 (10.00) 30-Day Readmission, n (%) 4 (22.22) 6 (22.22) 0 (0.00) 5 (25.00) 15 (21.43) 90-Day Readmission, n (%) 6 (33.33) 9 (33.33) 0 (0.00) 8 (40.00) 23 (32.86) 90-Day Mortality, n (%) 3 (16.67) 7 (25.93) 0 (0.00) 2 (10.00) 12 (17.14) The odds of developing 90-day outcomes comparing different COVID-19 waves against each other Outcome Wave 1*OR [95% CI] Wave 2*OR [95% CI] Wave 3*OR [95% CI] Wave 4*OR [95% CI] 90-Day CDI Recurrence Wave 1 1 Wave 2 2.96 [0.3 - 28.88] 1 Wave 3 4.25 [0.22 - 83.52] 1.44 [0.13 - 16.41] 1 Wave 4 0.89 [0.05 - 15.44] 0.30 [0.03 - 2.94] 0.21 [0.01 - 4.12] 1 90-Day Readmission Wave 1 1 Wave 2 1.00 [0.24 - 4.20] 1 Wave 3 -- -- 1 Wave 4 1.17 [0.26 - 5.24] 1.33 [0.4 - 4.43] -- 1 90-Day Mortality Wave 1 1 Wave 2 1.75 [0.39 - 7.91] 1 Wave 3 -- -- 1 Wave 4 0.56 [0.08 - 3.77] 0.32 [0.06 - 1.73] -- 1 Comparison of CDI outcomes in patients with COVID-19 against a historical group from 2019 Outcome CDI and COVID-19 (All 4 COVID-19 waves combined) n = 70 CDI in 2019 n = 458 P-Value 30-Day Readmission, n (%) 15 (21.43) 142 (31.00) 0.122 90-Day Readmission, n (%) 23 (32.86) 223 (48.69) 0.015 30-Day Mortality, n (%) 10 (14.29) 63 (13.76) 0.854 90-Day Mortality, n (%) 12 (17.14) 93 (20.31) 0.631 *Reference group.