Impact of COVID-19 and Antibiotic Treatments on Gut Microbiome: A Role for Enterococcus spp.

Abstract

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.

Gut microbiota in patients with COVID-19 and type 2 diabetes: A culture-based method

“…The exact role of Enterococcus in COVID-19 is not yet fully understood, but some researchers believe that it may play a role in the development of severe illness. For example, it has been proposed that Enterococcus may contribute to the development of cytokine storm, which is a severe immune response that can occur in some COVID-19 patients ( Zuo et al., 2020 ; Gago et al., 2022 ; Righi et al., 2022 ; Toc et al., 2022 ). The exact mechanism by which Enterococcus may contribute to cytokine storm is not well understood, but it is suggested that it may involve the activation of Toll-like receptors (TLRs), which are proteins on the surface of immune cells that recognize specific microbial products ( Guiton et al., 2013 ).…”

“…In our opinion, the possible increase in the abundance of Enterococcus spp. is related to the widespread use of carbapenems during the delta wave of COVID-19 in our region ( Righi et al., 2022 ).…”

T Cell Receptor Sequences Amplified during Severe COVID-19 and Multisystem Inflammatory Syndrome in Children Mimic SARS-CoV-2, Its Bacterial Co-Infections and Host Autoantigens

“…Normal TCR Sources: 100 randomly selected entries from [151] and: [8,152]. COVID-19 TCR Sources: [65,[153][154][155][156]. MIS-C TCR Sources: [47,157].…”

“…Enterococcus infections are particularly associated with the risk of hospitalization, admission to intensive care, and the increased risk of mortality in COVID-19 patients [65][66][67]. These bacterial infectious would therefore be expected to have been present in a significant proportion of severe COVID-19 patients from which the TCRs utilized in this study were derived and because of the severity of their disease, these patients would also be at the highest risk for developing autoimmune complications [28,[33][34][35][36][37][38][39][40]45].…”

“…Some of these bacteria are also associated with an increased risk of autoimmune myo- and endocarditis in COVID-19 including Streptococcus mitis and oralis , Enterococcus faecalis , Staphylococcus aureus , or coagulase-negative staphylococci [ 62 , 63 , 64 ]. Enterococcus infections are particularly associated with the risk of hospitalization, admission to intensive care, and the increased risk of mortality in COVID-19 patients [ 65 , 66 , 67 ]. These bacterial infectious would therefore be expected to have been present in a significant proportion of severe COVID-19 patients from which the TCRs utilized in this study were derived and because of the severity of their disease, these patients would also be at the highest risk for developing autoimmune complications [ 28 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 45 ].…”