Clostridioides difficile infection following COVID-19: A nationwide analysis using routine surveillance data in Wales.

Background: CDI incidence has increased in Wales from summer 2020 and has remained elevated. There is evidence of poorer outcomes from concurrent CDI and COVID-19 infections, but it is not clear if infection with COVID-19 directly impacts likelihood of CDI infection.

Aim: We investigated the relationship between CDI and COVID-19 and the impact of secondary infections.

Methods: We conducted two analytical studies using routine surveillance data: i) population level ecological case control study comparing CDI cases in the Welsh population by SARS-COV-2 exposure in the previous 90 days, ii) cohort study of COVID-19 cases by secondary infection presence, investigating CDI development within 90 days.

Findings: Case control: 12% (196/1645) of CDI cases had prior COVID-19 and were twice as likely to have had COVID-19 compared to general population controls, when controlling for other infection history (OR 2.1, CI 1.8-2.5, p<0.0001). CDI cases were 8 times more likely to have had other infections, independent of COVID-19 history (OR 8.0, CI 7.0-9.0, p<0.001).

Cohort study: 2% (2,255/137,620)) of the COVID-19 cohort developed >1 secondary infection, and <1% (185/137620) developed CDI within 90 days. CDI risk was four times higher in those with secondary infections, after age and sex adjustment (RR 4.6, CI 3.1 - 6.1, p<0.001). CDI risk increased with age and did not differ by sex.

Conclusions: Findings suggest a relationship between COVID-19 and CDI. However, incidence of CDI following COVID-19 was a rare outcome generally, suggesting other factors are likely contributing to the increased rates of CDI observed since 2020.