The lower respiratory tract microbiome of critically ill patients with COVID-19

Gaibani, Paolo; Viciani, Elisa; Bartoletti, Michele; Lewis, Russell E.; Tonetti, Tommaso; Lombardo, Donatella; Castagnetti, Andréa; Bovo, Federica; Horna, Clara Solera; Ranieri, Marco; Viale, Pierluigi; Re, Maria Carla; Ambretti, Simone

doi:10.1038/s41598-021-89516-6

Cited by 63 publications

(60 citation statements)

References 26 publications

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“…A study performed with 24 critically ill COVID-19 patients and 24 non-COVID-19 patients with pneumonia [38] showed taxonomical differences between the lung microbiota of Future research to determine their roles in COVID-19 development and evolution is required.…”

Section: Discussionmentioning

confidence: 99%

Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area

Ventero

Moreno-Pérez

Molina-Pardines

et al. 2021

Preprint

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Background: There is mounting evidence suggesting that the microbiome composition could be different in COVID-19 patients. However, the relationship between microbiota and COVID-19 severity progression is still being assessed. This study aimed to analyse the diversity and taxonomic composition of the nasopharyngeal microbiota, to determine its association with COVID-19 clinical outcome. Methods and Findings: Samples came from a retrospective cohort of adult patients with COVID-19, hospitalised in a tertiary centre. To study the nasopharyngeal microbiota, we utilized 16S rRNA sequencing. Raw sequences were processed by QIIME2. The associations between the microbiota, invasive mechanical ventilation (IMV), and all-cause mortality were analysed by multiple logistic regression (OR; 95%CI), adjusted for age, gender, and comorbidity. 177 patients were included: median age 68.0 years, 57.6% males, 59.3% had a Charlson comorbidity index ≥3, and 89.2% with pneumonia. The microbiota α diversity indexes were lower in patients with a fatal outcome, and this association persisted after adjustment for the main confounders; whereas the β diversity analysis showed a significant clustering, grouping the patients with a fatal outcome. After multivariate adjustment, the presence of Selenomonas spp., Filifactor spp., Actinobacillus spp., or Chroococcidiopsis spp., was associated with a reduced risk of IMV (adjusted OR 0.06[95%CI 0.01–0.047], p = 0.007). Conclusions: The microbiota diversity and taxonomic composition are related to COVID-19 severity. Higher diversity and the presence of certain genera in the nasopharyngeal microbiota seem to be early biomarkers of a favourable clinical evolution in hospitalised patients with moderate to severe SARS-CoV-2 infections.

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Section: Discussionmentioning

confidence: 99%

Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area

Ventero

Moreno-Pérez

Molina-Pardines

et al. 2021

Preprint

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“…An Italian paper showed bronchoalverolar lavage from 24 critically ill COVID-19 patients tended to grow gram-negative bacteria "predisposed to multidrug resistance" while 24 matched non-COVID-19 controls had more commensal flora such as Haemophilus sp. and streptococci [ 61 ]. Another reported 7 relatively young COVID-19 ICU patients with few comorbidities except obesity harbored carbapenemase-producing Klebsiella pneumoniae [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Bacterial and fungal growth in sputum cultures from 165 COVID-19 pneumonia patients requiring intubation: evidence for antimicrobial resistance development and analysis of risk factors

Liu

Yaron

Piraino

et al. 2021

Ann Clin Microbiol Antimicrob

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Background Coronavirus SARS-CoV-2 causes COVID-19 illness which can progress to severe pneumonia. Empiric antibacterials are often employed though frequency of bacterial coinfection superinfection is debated and concerns raised about selection of bacterial antimicrobial resistance. We evaluated sputum bacterial and fungal growth from 165 intubated COVID-19 pneumonia patients. Objectives were to determine frequency of culture positivity, risk factors for and outcomes of positive cultures, and timing of antimicrobial resistance development. Methods Retrospective reviews were conducted of COVID-19 pneumonia patients requiring intubation admitted to a 1058-bed four community hospital system on the east coast United States, March 1 to May 1, 2020. Length of stay (LOS) was expressed as mean (standard deviation); 95% confidence interval (95% CI) was computed for overall mortality rate using the exact binomial method, and overall mortality was compared across each level of a potential risk factor using a Chi-Square Test of Independence. All tests were two-sided, and significance level was set to 0.05. Results Average patient age was 68.7 years and LOS 19.9 days. Eighty-three patients (50.3% of total) originated from home, 10 from group homes (6.1% of total), and 72 from nursing facilities (43.6% of total). Mortality was 62.4%, highest for nursing home residents (80.6%). Findings from 253 sputum cultures overall did not suggest acute bacterial or fungal infection in 73 (45%) of 165 individuals sampled within 24 h of intubation. Cultures ≥ 1 week following intubation did grow potential pathogens in 72 (64.9%) of 111 cases with 70.8% consistent with late pneumonia and 29.2% suggesting colonization. Twelve (10.8% of total) of these late post-intubation cultures revealed worsened antimicrobial resistance predominantly in Pseudomonas, Enterobacter, or Staphylococcus aureus. Conclusions In severe COVID-19 pneumonia, a radiographic ground glass interstitial pattern and lack of purulent sputum prior to/around the time of intubation correlated with no culture growth or recovery of normal oral flora ± yeast. Discontinuation of empiric antibacterials should be considered in these patients aided by other clinical findings, history of prior antimicrobials, laboratory testing, and overall clinical course. Continuing longterm hospitalisation and antibiotics are associated with sputum cultures reflective of hospital-acquired microbes and increasing antimicrobial resistance. Trial registration: Not applicable as this was a retrospective chart review study without interventional arm.

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“…On the contrary, the lung microbiome in COVID-19-negative pneumonia patients was mainly characterized by the enrichment of Haemophilus influenzae , Veillonella dispar , Granulicatella sp., Porphyromonas sp., and Streptococcus sp. [ 91 ]. Several studies have already reported that respiratory virus infections can alter the microbial composition and total amount of bacterial load [ 21 , 92 ].…”

Section: The Lung Microbiome During Diseasementioning

confidence: 99%

“…Recent studies showed that gut microbiome composition differed significantly among COVID-19 patients compared with non-COVID-19 individuals [ 91 , 92 ]. Besides, plasma concentrations of inflammatory cytokines, chemokines, and tissue damage markers are correlated with gut microbiota composition.…”

Section: The Lung Microbiome During Diseasementioning

confidence: 99%

The Lung Microbiome during Health and Disease

Yagi

Huffnagle

Lukacs

et al. 2021

IJMS

111

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Healthy human lungs have traditionally been considered to be a sterile organ. However, culture-independent molecular techniques have reported that large numbers of microbes coexist in the lung and airways. The lungs harbor diverse microbial composition that are undetected by previous approaches. Many studies have found significant differences in microbial composition between during health and respiratory disease. The lung microbiome is likely to not only influence susceptibility or causes of diseases but be affected by disease activities or responses to treatment. Although lung microbiome research has some limitations from study design to reporting, it can add further dimensionality to host-microbe interactions. Moreover, there is a possibility that extending understanding to the lung microbiome with new multiple omics approaches would be useful for developing both diagnostic and prognostic biomarkers for respiratory diseases in clinical settings.

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The lower respiratory tract microbiome of critically ill patients with COVID-19

Cited by 63 publications

References 26 publications

Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area

Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area

Bacterial and fungal growth in sputum cultures from 165 COVID-19 pneumonia patients requiring intubation: evidence for antimicrobial resistance development and analysis of risk factors

The Lung Microbiome during Health and Disease

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