All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort

Abstract

Purpose: Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary.

Methods: 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account.

Results: Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05).

Conclusion: In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.

Keywords: Antibiotic stewardship; Antibiotics; COVID-19; LEOSS; Procalcitonin.

Fig. 1

Flowchart showing the inclusion criteria for the analysis. LEOSS: Lean European Open Survey on SARS-CoV-2-Infected Patients

Fig. 2

Clinical symptoms and characteristics defining the different phases (uncomplicated [UC], complicated [CO], critical [CR] and recovery) in the LEOSS cohort. The alternative endpoint “death” is not displayed in this figure

Fig. 3

Illustration of antibiotic treatment by clinical phase and antibiotic class. Complicated phase patients are additionally stratified by procalcitonin. Relative percentages are indicated visually by the length of the boxes. Absolute numbers are printed into or next to the respective box. Some antibiotic groups include additional cases not counted in the subgroups due to the documentation process (e.g., “Betalactams”, includes “Penicillin/ Piperacillin”, “Cephalosporins”, “Carbapenems”. “New betalactams” and Betalactams where the exact type is not specified). A patient can both show up in multiple phases (disease progression) and in multiple antibiotic classes (e.g., multiple antibiotic classes used for treatment), but will be counted once only for a given antibiotic class in a phase (e.g., multiple Betalactam treatments of the same subgroup will be counted as one)