Understanding the microbial composition of the respiratory tract in hospitalized Covid-19 patients

Hein Min Tun’s team, in collaboration with colleagues from Denmark, Guangzhou, and Shenzhen among others, have studied the characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients. This study published in Nature’s Cell Discovery focuses on the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19.


From the identification of distinct signatures of microbial dysbiosis among severely ill Covid-19 patients, their work highlights the need for adapted detection and tracking strategies to prevent the spread of antimicrobial resistance and improve the clinical outcomes of hospitalized patients.


>>> Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients


Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

a Presence/absence profile of nonviral microbial genera in mild and severe cases. Orange, mild; brick red, severe. Only common genera detected in over 60% of patients in the mild cases (n > 4) or severe cases (n > 7) are shown. b Bar plot showing the relative expression levels of nonviral microbes in all respiratory specimens of mild (orange, n = 7) and severe cases (brick red, n = 40). c Relative expression levels of selected genera differing between mild and severe cases. The bar chart and black error bars denote the mean and standard error values of expression levels in mild (orange) and severe (brick red) cases for each genus. ***P < 0.001; **P < 0.01; *P < 0.05; Wilcoxon rank-sum test. For patients with multiple respiratory specimens (all were severe cases), the presence of a given genus is considered when at least one sample from this patient was positive for the taxon (relative abundance > 0) (a), and the comparisons between relative expression levels of selected genera are conducted across all collected respiratory samples between mild and severe cases (c).