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

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.

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

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.

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).

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.

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.