Shifts in the Respiratory Microbiome and Clinical Outcomes of SARS-CoV-2 (COVID-19)

A Longitudinal Observational Study Identifying Shifts in the Respiratory Microbiome and Clinical Outcomes of SARS-CoV-2 in Nursing Home Residents

This is a longitudinal, prospective observational study focusing on health-related outcomes relative to potential changes in the respiratory microbiome seen with weekly SARS-CoV-2 testing in nursing home residents.

Study Overview

• Status: Terminated
• Conditions: SARS-CoV-2 Infection; Viral Respiratory Tract Infection; Bacterial Respiratory Tract Infection

Detailed Description

This study targets the influence of SARS-CoV-2, and the presence of mixed/co-infections on the respiratory microbiome. Their interrelationship will be characterized in a prospective observational study design. The observed changes will be correlated to medical (FEV1, CXR/CT, mortality, morbidity, symptoms) and clinical laboratory parameters (hematology, coagulation, bacterial/viral detection). The study aims at the detection of significant changes in microbiome in the respiratory tract following incidence of SARS-CoV-2 infection. These alterations in the respiratory microbiome will be determined by shotgun metagenomic sequencing. Ultimately, this can provide a better understanding of how SARS-CoV-2 and the presence of other bacteria and viruses affect the composition of the respiratory microbiome and a description of the microbiological etiology of these respiratory tract infections.

• Study Type: Observational
• Enrollment (Actual): 185

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Delaware, Ohio, United States, 43015
      • Willow Brook Christian Village
    • Delaware, Ohio, United States, 43015
      • Willow Brook Delaware Run
    • Granville, Ohio, United States, 43023
      • Kendall at Granville
    • Westerville, Ohio, United States, 43081
      • Inniswood Village

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Newly recruited patients are older adults (≥ 65 years) and pre-geriatric (≥60 years and <65 years) residents of nursing homes who have recently been identified as SARS-CoV-2 positive through Ohio's PARRT Program.

Subjects currently enrolled are older adults (≥ 65 years) and pre-geriatric (≥60 years and <65 years) residents of nursing homes

Description

Inclusion Criteria:

• All residents of the nursing home facility, (M/F) 65 years or above, who have recently tested positive through Ohio's PARRT Program are eligible
• Resident must submit weekly nasal swab sample per nursing home COVID testing guidelines
• Clinical suspicion of a new episode of acute respiratory tract infection.
• Laboratory confirmed SARS-CoV-2 infection by either a laboratory test, PCR or any other commercial or public health test

Exclusion Criteria:

• Nursing home residents that are not taking part regularly in weekly screening for SARS-COV-2 or residents that test negative through Ohio's PARRT program cannot be included as part of study analyses
• Residents on hospice, residents currently intubated, residents with scheduled transfer to another nursing home facility will not be included in study analyses

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients with New Cases of SARS-CoV-2; Newly recruited residents who have been identified as positive through Ohio's Post-Acute Regional Rapid Testing (PARRT) Program will undergo at at least 4 weeks, but no more than 8 weeks, of nasal swab and exhaled breathe particles specimen collection for Covid testing. Previously enrolled residents will submit weekly collections of nasal swab specimens and exhaled breathe particles once they exhibit respiratory-related symptoms, or once a test is ordered by the provider for suspicion of exposure. Collection will continue until these subjects fulfill their 8 weeks of testing.
Patients without SARS-CoV-2; This cohort will consist of previously enrolled residents who submitted nasal swabs and exhaled breathe particles for Covid testing once a week for 8 weeks. The patients will have been identified as negative for a SARS-CoV-2 infection each week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of SARS-CoV-2 infection	Examine prospective data to determine the change from baseline (week 1 of testing) in resident/bed ratio positive for SARS-CoV-2.	4-8 weeks
Percent of SARS-CoV-2 and bacterial co-infection	Examine prospective data to determine the change from baseline number of healthy [SARS-CoV-2 naïve] to number that develop respiratory tract infection. Percent of SARS-CoV-2 positives without a bacterial source of RTI compared to percent of SARS-CoV-2 positives with bacterial co-infection identified by either PCR, symptoms, CXR, CT, throat culture swab, RDT and documented in patient chart.	4-8 weeks
Percent of SARS-CoV-2 and viral co-infection	Examine prospective data to determine the change from baseline number of healthy [SARS-CoV-2 naïve] to number that develop respiratory tract infection. Percent of SARS-CoV-2 positives without an additional viral cause identified compared to percent of SARS-CoV-2 positives with viral co-infection identified.	4-8 weeks
Mortality rate due to SARS-CoV-2 infection with bacterial/viral co-infection	Examine prospective data to determine the mortality rate (outpatient and inpatient) due to SARS-CoV-2 with additional bacteria and/or virus identified at any time during SARS-Cov-2 PCR positivity prior to death.	12 months
Mortality rate due to SARS-CoV-2 infection	Examine prospective data to determine the mortality rate (outpatient and inpatient) due to SARS-CoV-2 only (no additional bacteria and/or virus identified on PCR at any time during SARS-CoV-2 PCR positivity prior to death.	12 months
Symptoms of SARS-CoV-2 infection, bacterial co-infection, viral co-infection	Any changes in symptom severity will be captured by monitoring the patient's chart for any updates in clinical progress notes. Any symptoms compatible with SARS-CoV-2 infection will be captured such as high temperature, dyspnea, diarrhea, vomiting, myalgia, pharynx pain, abdominal pain, anosmia, cough etc.	Up to 12 weeks post-PCR confirmation for a SARS-CoV-2 positive diagnosis
Percent of SARS-Cov-2 positives and/or bacterial/viral infection with full resolution by 30 days	Examine prospective data to determine the percent of SARS-Cov-2 positives and/or bacterial/viral infection with full resolution by 30 days after respiratory symptom onset [full resolution defined as resolution of acute onset clinical symptoms].	Up to 30 days after respiratory symptom onset
Percent of SARS-Cov-2 positives and/or bacterial/viral infection that develop pneumonia-like symptoms	Examine prospective data to determine the percent of SARS-Cov-2 positives and/or bacterial/viral infection that develop pneumonia-like symptoms during SARS-CoV-2 PCR positivity	4-8 weeks
Percent of asymptomatic SARS-Cov-2 positives and/or bacterial/viral infection	Examine prospective data to determine the percent of asymptomatic SARS-Cov-2 positives and/or bacterial/viral infection that never develop symptoms throughout infectious period and are alive/healthy at end of study.	4-8 weeks
Percent of pre-symptomatic SARS-Cov-2 positives and/or bacterial/viral infection	Examine prospective data to determine the percent of pre-symptomatic SARS-CoV-2 positives and/or bacterial/viral infection. This is the asymptomatic period PRIOR to a symptomatic period all during time of PCR positivity.	4-8 weeks
Percent of all acute medical complications	Examine prospective data to determine the prevalence of all medical usual complications and geriatric acquired complications, such as delirium, falls, pressure sores, new infectious disease (UTI), cardiovascular, incidence of acute heart failure [elevated BNP presence of new ECG abnormalities (ST elevation and/or T-wave inversion), myocardial injury [reflected by elevation in cardiac troponin levels above the 99th percentile upper reference limit on admission, cerebrovascular disease [Stroke, stroke subtype (ischemic, cryptogenic , metabolic disease manifestations DKA, hyperosmolar hyperglycemic state (HHS), and severe insulin resistance, Neurological Manifestations [Anosmia/dysgeusia, Guillen Barre Syndrome, Meningoencephalitis, Encephalomyelitis, myoclonus (generalized), Rhabdomyolysis, VTE, DIC, PE, acute limb ischemia	4-8 weeks
Pulmonary function	Examine prospective data to determine the the percent change in forced vital capacity (FVC), forced expiratory volume (FEV1), peak expiratory flow (PEF) in patients	Baseline to any timepoint for 4 to 8 weeks
Chest CT X-ray	Examine prospective data to determine the percent of lung CT containing consolidation, percent of patients showing reticular patterns, percent containing pure ground-glass opacification, percent containing honeycomb appearance, percent containing Bronchiectasis	Baseline to any timepoint for 4 to 8 weeks
Changes in hematology	Examine prospective data to identify changes in patient hematology through analysis of complete blood routines for CBC and WBC.	Baseline to any timepoint for 4 to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALPHA Diversity (determined by NGS)	Defined as intra-community diversity as measured by the total number of detected taxa and distribution of those taxa.	6-12 months
Taxon Identification (determined by NGS)	Defined as intra-community diversity as measured by the total number of detected taxa and distribution of those taxa.	6-12 months
BETA Diversity (determined by NGS)	Defined as inter-community diversity as measured by the total number of detected taxa and distribution of those taxa.	6-12 months
Frequency of Detection (Determined by NGS)	Frequency of detection of the total amount of bacterial DNA/RNA that corresponds to specific bacterial taxa found within nasal swab/ exhaled breath	6-12 months

Collaborators and Investigators

• Sponsor: Pathnostics
• Investigators: Principal Investigator: Alan Wolfe, MD, Loyola University Chicago; Principal Investigator: Kirk Wojno, MD, Comprehensive Urology; Principal Investigator: John Weigand, MD, Central Ohio Geriatrics

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 7, 2020
• Primary Completion (ACTUAL): May 30, 2021
• Study Completion (ACTUAL): May 30, 2021

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (ACTUAL): March 24, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 30, 2021
• Last Update Submitted That Met QC Criteria: June 25, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; Nursing Home; Respiratory Microbiome
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: 2020-rmcovid

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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