Characterization Immunology, Biochemical and Lung Microbiome, Correlated With the Ventilation Associated Pneumonia (VAP) (MicroNAV-II)

Characterization of Cellular Immunology, Biochemical and Lung Microbiome, Correlated With the Development of Ventilation Associated Pneumonia (VAP) in Adult Patients Admitted to the Intensive Care Unit (ICU): The Second Stage.

SARS-CoV-2, the virus that causes COVID-19, is currently a global public health problem, declared a pandemic by the World Health Organization, which today has more than one million deaths in the world, of which , 30,000 approximately belong to Colombia, being the country number 11 with the highest number of deaths. The most common symptoms related to this disease are fever, cough, dyspnea, myalgia, headache, diarrhea and rhinorrhea. COVID-19 is characterized by immune system dysfunction and hyperinflammation causing acute respiratory distress syndrome, macrophage activation, and coagulopathy. The clinical course for SARS-CoV-2 in most cases is mild, but approximately 14% of cases can be severe. In pneumonia caused by SARS-CoV-2, the lung lining is known to alter the composition of the lung microbiome, in addition to lymphocyte damage that can promote the growth of bacteria to initiate bacterial pneumonia, and it is estimated that the prevalence of coinfection / superinfection reaches 50% among deaths from COVID-19. Coinfection between different microorganisms and SARS-CoV-2 is a serious problem in the COVID-19 pandemic, and there is still little information on this.

It is for this reason that the researchs propose to develop this research project that will allow to understand the possible mechanisms associated with the development of bacterial coinfection / superinfection in patients diagnosed with COVID-19, which will allow expanding the panorama of knowledge towards a better and adequate treatment in these patients, as well as detection of biomarkers or clinical phenotypics that may be useful in the diagnosis, based on evidence.

It is important to note that these results are of clinical importance since we will try to identify biomarkers or changes in the lung microbiome that allow doctors to early identify patients at risk of developing coinfection and thus initiate early treatments or preventive measures, which allow the improvement of clinical outcomes in patients. Results will be presented in a timely manner at national and international conferences and in peer-reviewed, indexed, high-impact journals.

Study Overview

• Status: Not yet recruiting
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Other: Clinical follow-up for 24 months

Detailed Description

This is a prospective, translational (T0-T2), multicenter, observational, cohort study of consecutive patients with a first clinical phase, where the collection of different types of samples (Bronco alveolar lavage, blood, nasopharyngeal swab, secretion orotracheal and rectal swabbing) at the start of mechanical ventilation, on day 3 and before extubation and another stage of molecular analysis in human samples collected where by different types of techniques such as: characterization of the 16S ribosomal unit, ELISA, time PCR real, concentration and cell discrimination techniques, we will characterize the microbiological, immunological and cellular changes that condition the development of coinfection.

Descriptive analytical studies, techniques, and parametric and nonparametric tests will be used to explore diagnostic, microbiological, or subgroup differences, as well as clinical outcomes. Independent predictors and associated hazard ratios with 95% confidence intervals will be reported. A two-tailed p value less than 0.05 will be considered statistically significant.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Luis F Reyes, MD; Phone Number: +57 3175130128; Email: luis.reyes5@unisabana.edu.co
• Study Contact Backup: Name: Ingrid G Bustos, BsC; Phone Number: +57 3115421277; Email: ingrid.bustos2@unisabana.edu.co

Study Locations

• Colombia
  • Cundinamarca
    • Chía, Cundinamarca, Colombia
      • Clínica Universidad de La Sabana
      • Contact: Luis F Reyes, MD; Phone Number: +57 3175130128; Email: luis.reyes5@unisabana.edu.co
      • Principal Investigator: Luis F Reyes, MD
      • Contact: Ingrid G Bustos, BsC; Phone Number: +57 3115421277; Email: ingridbusmo@unisabana.edu.co
      • Sub-Investigator: Ingrid G Bustos, Bsc

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: Probability Sample

Study Population

Adult patients admitted to the Intensive Care Unit of the Clínica Universitaria de la Sabana, with a diagnosis of COVID-19 by RT-PCR, who require invasive mechanical ventilation due to respiratory failure as a result of the infection and who approve their participation in the study. It is important to highlight that these patients are sedated and cannot agree to participate in the study; therefore, the patient's relatives or legal representative will be in charge of defining the participation of the relative in the study.

Description

Inclusion Criteria:

• Patients admitted to the ICU, COVID-19 positive by RT-PCR, who require assisted mechanical ventilation.
• Adult patients over 18 years of age.
• Patients who agree to participate in the study and sign the informed consent form (family members or legal representative).
• Patients in whom the identification of the causative agent of coinfection is attempted within the first 48 hours of hospitalization.

Exclusion Criteria:

• Patient on mechanical ventilation for more than 24 hours without being evaluated for study entry.
• Patient who was treated with antibiotics 7 days prior to hospitalization or time of assessment for the study.
• Pregnant or breastfeeding patients.
• People who belong to population groups with increased vulnerability such as, for example, prison population, minors detained in orphanages or people in street situations.

No research procedure, clinical or paraclinical, or taking of clinical information or biological samples will be performed before the patient or his/her legal representative agrees to participate in the study and signs the informed consent form.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with COVID 19 infection who develop bacterial coinfection.; Follow-up for 24 months	Other: Clinical follow-up for 24 months; Sampling and clinical follow-up for 24 months
Patients with COVID 19 infection who do not develop bacterial coinfection.; Follow-up for 24 months	Other: Clinical follow-up for 24 months; Sampling and clinical follow-up for 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of the pulmonary microbiome and changes in microbial diversity in patients with severe COVID.	To observe the change that occur in the diversity of the pulmonary microbiome in patients with severe COVID, with mechanical ventilation. The pulmonary microbiome will be analyzed at 4 four times during the patient's mechanical ventilation (baseline, 72 hours, fifth day, seventh day or if he/she develops co-infection or superinfection).	24 months
Correlation between microbial diversity and host immune response with severe COVID.	To analyze whether changes in microbial diversity have any association with the host immune response leading to increased susceptibility to co-infection or superinfection during COVID disease.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of coinfected/overinfected patients with severe COVID and the diversity of the pulmonary microbiome.	To observe patterns of lung microbiome diversity in patients with severe COVID that will help us predict the development of coinfection or superinfection in these patients.	24 months
Immunologic or cellular patterns in coinfection or superinfection in patients with severe COVID.	To describe immunological or cellular patterns in patients with severe COVID that will help us predict the development of coinfection or superinfection in these patients.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of specimen and conventional cultures for the diagnosis of coinfection or superinfection in patients with severe COVID.	To evaluate three types of respiratory samples by conventional culture for the diagnosis of coinfection or superinfection. This will be compared with the findings of genomic sequencing to be performed to determine the pulmonary microbiome.	24 months

Collaborators and Investigators

• Sponsor: Universidad de la Sabana

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: June 21, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Covid19; SARS-CoV Infection; pulmonary microbiome
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Pneumonia
• Other Study ID Numbers: MED-286-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: confidentiality agreement

Drug and device information, study documents

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