The impact of immunosuppressive therapy on secondary infections and antimicrobial use in COVID-19 inpatients: a retrospective cohort study

Background: Immunosuppressive therapies have become a cornerstone of the management of severe COVID-19. The impact of these therapies on secondary infections and antimicrobial prescribing remains unclear. We sought to assess antimicrobial use and the incidence of bacterial and fungal infections in patients with severe COVID-19, and to explore their associations with receipt of immunosuppressive therapies.

Methods: Our retrospective cohort study included 715 hospitalised, adult patients with severe COVID-19 admitted to St George's Hospital, London, UK, during the first UK pandemic wave (1^st March-10^th June 2020). Co-infections (occurring within 48 h of admission) and secondary infections (≥ 48 h) were defined as a positive microbiological culture with supporting clinical, radiological or laboratory data to suggest true infection. Cox regression models with time-dependent covariates were used to explore the association between immunosuppressant use and secondary infection.

Results: Microbiologically confirmed co-infection occurred in 4.2% (n = 30) and secondary infection in 9.3% (n = 66) of the cohort (n = 715) and were associated with in-hospital mortality (48% vs 35%, OR 1.8, 95%CI 1.1-2.7, p = 0.01). Respiratory (n = 41, 39%) and bloodstream infections (n = 38, 36%) predominated, with primarily Gram-negative pathogens. 606 (84.7%) patients received an antimicrobial, amounting to 742 days of therapy per 1000 patient-days (DOTs). In multivariable models, receipt of high-dose steroids (≥ 30 mg prednisolone or equivalent) or tocilizumab was significantly associated with increased antimicrobial consumption (+ 5.5 DOTs, 95%CI 3.4-7.7 days) but not secondary infection (HR 0.56, 95%CI 0.26-1.18).

Conclusions: Bacterial and fungal infections in severe COVID-19 were uncommon. Receipt of steroids or tocilizumab was independently associated with antimicrobial consumption despite its lack of association with secondary infection. These findings should galvanise efforts to promote antimicrobial stewardship in patients with COVID-19.