Oropharyngeal and intestinal concentrations of opportunistic pathogens are independently associated with death of SARS-CoV-2 critically ill adults

Abstract

Background The composition of the digestive microbiota may be associated with outcome and infections in patients admitted to the intensive care unit (ICU). The dominance by opportunistic pathogens (such as Enterococcus) has been associated with death. However, whether this association remains all throughout the hospitalization are lacking. Methods We performed a single-center observational prospective cohort study in critically ill patients admitted with severe SARS-CoV-2 infection. Oropharyngeal and rectal swabs were collected at admission and then twice weekly until discharge or death. Quantitative cultures for opportunistic pathogens were performed on oropharyngeal and rectal swabs. The composition of the intestinal microbiota was assessed by 16S rDNA sequencing. Oropharyngeal and intestinal concentrations of opportunistic pathogens, intestinal richness and diversity were entered into a multivariable Cox model as time-dependent covariates. The primary outcome was death at day 90. Results From March to September 2020, 95 patients (765 samples) were included. The Simplified Acute Physiology Score 2 (SAPS 2) at admission was 33 [24; 50] and a Sequential Organ Failure Assessment score (SOFA score) at 6 [4; 8]. Day 90 all-cause mortality was 44.2% (42/95). We observed that the oropharyngeal and rectal concentrations of Enterococcus spp., Staphylococcus aureus and Candida spp. were associated with a higher risk of death. This association remained significant after adjustment for prognostic covariates (age, chronic disease, daily antimicrobial agent use and daily SOFA score). A one-log increase in Enterococcus spp., S. aureus and Candida spp. in oropharyngeal or rectal swabs was associated with a 17% or greater increase in the risk of death. Conclusion We found that elevated oropharyngeal/intestinal Enterococcus spp. S. aureus and Candida spp. concentrations, assessed by culture, are associated with mortality, independent of age, organ failure, and antibiotic therapy, opening prospects for simple and inexpensive microbiota-based markers for the prognosis of critically ill SARS-CoV-2 patients.

Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19

“…Our study expands the current literature by reporting a potential link between ICU-related microbiota alterations and 60 days mortality, in line with a recent study showing an association between day-90 mortality and higher concentrations of opportunistic pathogens in the oropharyngeal and intestinal compartments of critically ill patients [ 13 ]. Of note, our data should be interpreted with caution, as our sample size was not powered for multivariate adjustment.…”

“…12 Department of Internal Medicine, Baerum Hospital, Vestre Viken Hospital Trust, 1346 Gjettum, Norway. 13 Department of Anesthesiology and Intensive Care, Hammerfest County Hospital, Hammerfest, Norway. 14 Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo,…”

“…It has been hypothesized that COVID-related gut microbiota alterations (dysbiosis) could promote long-term clinical outcome [ 12 ]. A recent study of critically ill COVID-19 patients based on selective bacterial cultures and subsequent sequencing reported that higher concentrations of opportunistic pathogens in the oropharyngeal and intestinal compartments were independently associated with 90-day mortality [ 13 ]. However, data on sequencing-based gut microbiota dysbiosis and mortality are lacking.…”

Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis

“…A flourishing Enterococcus population often implies the fragile condition of the gut microbiota. Previous studies demonstrated that the elevated abundance of Enterococcus on admission was predictive of death or infection among ICU patients and was predictive of death from severe SARS-CoV-2 infection [ 33 – 35 ]. Moreover, our results demonstrate that Enterococcus exhibits a potent inhibitory association with most microbes and altered metabolites in sepsis patients.…”

Pathogenic Potential and Antibiotic Susceptibility: A Comprehensive Study of Enterococci from Different Ecological Settings

“…They also constitute the second most commonly reported cause of surgical wound infections and the third most often reported cause of bacteremia [33,34]. Moreover, enterococci have been reported as the main Gram-positive bacteria causing hospital-acquired infections during and after the COVID 19 pandemic [35][36][37][38][39][40].…”