Dynamic changes in the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its association with disease severity

Abstract Background The antibiotic resistome is the collection of all the antibiotic resistance genes (ARGs) present in an individual. Whether an individual’s susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is influenced by their respiratory tract antibiotic resistome is unknown. Additional, whether a relationship exists between the respiratory tract and gut antibiotic resistance genes composition has not been fully explored. Method We recruited 66 patients with COVID-19 at three disease stages (admission, progression and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Results Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrugand Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin and Fosmidomycinwere increased in ICU patients. Upon further investigation a significantly positive correlation was found between the relative abundance in ARGs (i.e., subtypes of the Aminoglycoside and Tetracyclinetypes) in the respiratory tract and gut. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in respiratory tract and gut. We found that immune related pathways in PBMC were enhanced, and they were significantly correlated with the relative abundance of Multidrug, Vancomycin and Tetracycline ARGs. Based on the relative abundance of ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. The level of Aminoglycoside and Vancomycinin the gut was regarded as the most prominent biomarker. Conclusions Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.