Objective: Several studies showed the substantial use of antibiotics and  increased risk of antimicrobial resistant infections in patients with  COVID-19. The impact of COVID-19-related treatments and antibiotics on  gut dysbiosis has not been clarified.

Design: The prospective cohort study included hospitalized COVID-19  patients (April-December 2020). The gut microbiome composition was  analysed by 16S sequencing. The gut diversity and changes in  opportunistic bacteria (OBs) or symbionts were analysed according to  clinical parameters, laboratory markers of disease progression, type of  non-antibiotic COVID-19 treatments (NACT) and type, WHO AWaRe group, and  duration of antibiotic therapy (AT).

Results: A total of 82 patients (mean age 66 ± 13 years, 70% males) were enrolled. The relative abundance of Enterococcus was significantly correlated with duration of hospitalization, intensive care unit stay, O2 needs, and D-dimer, ferritin, and IL-6 blood levels. The presence of Enterococcus showed the highest number of correlations with NACT, AT, and AT + NACT  (e.g., hydroxychloroquine ± lopinavir/ritonavir) and increased relative  abundance with AWaRe Watch/Reserve antibiotics, AT duration, and  combinations. Abundance of Dorea, Agathobacter, Roseburia, and Barnesiella was negatively correlated with AT and corticosteroids use. Patients  with increased IL-6, D-dimer, and ferritin levels receiving AT were more  likely to show dysbiosis with increased abundance of Enterococcus and Bilophila bacteria and decreased abundance of Roseburia compared with those not receiving AT.

Conclusion: Microbiome diversity is affected by COVID-19 severity. In this  context, antibiotic treatment may shift the gut microbiome composition  towards OBs, particularly Enterococcus. The impact of  treatment-driven dysbiosis on OBs infections and long-term consequences  needs further study to define the role of gut homeostasis in COVID-19  recovery and inform targeted interventions.