Role of the Microbiota in the Evolution of the SARS-CoV-2 Disease,COVID-19, in Hospitalized Patients (MicrobioCOVID)

Role of the Microbiota in the Evolution of the SARS-CoV-2 Disease in Hospitalized Patients

Patients hospitalized for COVID-19 may need intensive care (e.g. mechanical ventilation) during hospitalization. Some risk factors are already known but better targeting of such patients is still needed, at least because existing risk factors are not strong enough to provide an accurate prediction. Care organization would benefit for such a predictive tool.

Oropharyngeal and gut microbiota could potentially fill a significant gap in predictive performances. The investigators therefore propose to sample 200 patients (oropharyngeal and rectal swab) admitted in infectious disease department at Bichat Hospital and at high risk of needing intensive care during hospitalization. The investigators plan to perform metagenomic sequencing and bioinformatic analysis of these samples to characterize the diversity of bacterial species present in the oropharynx and the gut and to identify new factors associated with the need for intensive care. Aside metagenomic analyses, The investigators will perform semi-quantitative cultures of the oropharyngeal and gut microbiota to identify and quantify pathogens in order to predict the risk of bacterial infections in COVD-19 patients.

For patients transferred in intensive care unit, The investigators will to perform another series of samples to better characterize the evolution of microbiota during mechanical ventilation and identify factors associated with the risk of developing a ventilator-associated pneumonia.

Microbiota data will be considered together with the host genotype, the viral sequence and a deep immunological profiling to identify the main determinants of the evolution toward severity of COVID-19.

Study Overview

• Status: Recruiting
• Conditions: Covid19
• Intervention / Treatment: Other: oropharyngeal and intestinal microbiota; Other: host genotype; Other: host immune factors; Other: viral sequence

Detailed Description

Patients hospitalized for COVID-19 may need intensive care (e.g. mechanical ventilation) during hospitalization. Some risk factors are already known (e.g. sex, comorbidities, initial clinical presentation inflammatory cytokines), but better targeting of such patients is still needed, at least because existing risk factors are not strong enough to provide an accurate prediction. Care organization would benefit for such a predictive tool.

Oropharyngeal and gut microbiota could fill a significant gap in predictive performances. The investigators therefore propose to take advantage of the French-COVID cohort and sample 200 patients (oropharyngeal and rectal swab) admitted in infectious disease department at Bichat Hospital and at high risk of needing intensive care during hospitalization. The investigators plan to perform metagenomic sequencing and bioinformatic analysis of these samples to characterize the diversity of bacterial species present in the oropharynx and the gut and to identify new factors associated with the need for intensive care. Aside metagenomic analyses, The investigators will perform semi-quantitative cultures of the oropharyngeal and gut microbiota to identify and quantify pathogens in order to predict the risk of bacterial infections in COVD-19 patients.

The genetic determinants of the host (the patient) could also be predictive of the severity of the disease and so does the immunological response to the COVID-19. Likewise, it has been suggested that certain mutations (notably the D614G mutation) of the viral sequence could be associated with the infectivity of the virus.

In addition to the direct role of the microbiota in the course of infection, the immune characteristics specific to the host, by themselves or in interaction with the microbiota, could play an important role in the progression of the disease.

This project focuses on the clinical characterization of COVID-19 and its evolution, as well as disease management.

The research focuses on 4 main areas:

• Characterization of the oropharyngeal and intestinal microbiota of patients with COVID-19
• Characteristics of the host (genotype)
• Immune characteristics of the host
• Characteristics of the SARS-CoV-2 viral genome

For patients transferred in intensive care unit, The investigators will to perform another series of samples to better characterize the evolution of microbiota during mechanical ventilation and identify factors associated with the risk of developing a ventilator-associated pneumonia.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Etienne Ruppé; Phone Number: 33 1 40 25 80 00; Email: etienne.ruppe@aphp.fr
• Study Contact Backup: Name: Xavier Lescure; Phone Number: 33 1 40 25 80 00; Email: xavier.lescure@aphp.fr

Study Locations

• France
  • Paris, France
    • Recruiting
    • LESCURE
    • Contact: xavier lescure; Email: xavier.lescure@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patient with documented SARS-CoV-2 infection requiring hospitalization.

Description

Inclusion Criteria:

• Adult patient with documented SARS-CoV-2 infection requiring hospitalization.

Exclusion Criteria:

• Lack of consent
• Patients hospitalized in an intensive care unit
• Patient under guardianship or curatorship

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients hospitalized for COVID-19	Other: oropharyngeal and intestinal microbiota; analysis of oropharyngeal and intestinal microbiota; Other: host genotype; analysis of a part of host genotype; Other: host immune factors; analysis of host immune factors; Other: viral sequence; analysis of viral sequence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify risk factors associated with severe forms of COVID-19 requiring transfer to ICU	The main endpoint is the indication of worsening of the general condition requiring transfer to ICU	day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Link between the composition of the gut microbiota and admission to intensive care	Composition of the gut microbiota on admission to intensive care to predict the outcome of severe COVID-19 in patients transferred to the ICU (subgroup analysis)	3 months
Predictive performance of semi-quantitative culture and rapid metagenomic evaluation	Predictive performance of semi-quantitative culture and rapid metagenomic evaluation of the oropharyngeal microbiota to predict the occurrence of VAP in patients admitted to an ICU and mechanically ventilated (subgroup analysis).	3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2020
• Primary Completion (Actual): December 4, 2021
• Study Completion (Anticipated): August 31, 2022

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 24, 2022
• Last Update Submitted That Met QC Criteria: June 20, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors
• Other Study ID Numbers: APHP201083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No